start-ver=1.4 cd-journal=joma no-vol=79 cd-vols= no-issue=6 article-no= start-page=451 end-page=455 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recurrence of FVIII Inhibitor during Surgery in a Patient with Severe Hemophilia A Receiving Emicizumab Prophylaxis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Emicizumab, a bispecific monoclonal antibody, benefits patients with severe hemophilia A. It alters laboratory assessments of coagulation activity, requiring anti-idiotype monoclonal antibodies for accurate monitoring. A 64-year-old man, receiving emicizumab regularly, was admitted for laminoplasty. We planned to use FVIII replacement during the perioperative period after confirming the disappearance of inhibitors, monitoring coagulation activity with anti-idiotype monoclonal antibodies. Activated partial thromboplastin time was prolonged on postoperative day 2, prompting an immediate switch to eptacog alfa. The patient recovered without bleeding. This case underscores the necessity of anti-idiotype monoclonal antibodies for accurate monitoring. en-copyright= kn-copyright= en-aut-name=HagiharaMoe en-aut-sei=Hagihara en-aut-mei=Moe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HayashinoKenta en-aut-sei=Hayashino en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KinKyohei en-aut-sei=Kin en-aut-mei=Kyohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HirataYuichi en-aut-sei=Hirata en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Neurological Surgery, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Neurological Surgery, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Division of Transfusion and Cell Therapy, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=emicizumab kn-keyword=emicizumab en-keyword=eptacog alfa kn-keyword=eptacog alfa en-keyword=hemophilia A kn-keyword=hemophilia A en-keyword=inhibitor kn-keyword=inhibitor en-keyword=anti-idiotype monoclonal antibodies to emicizumab kn-keyword=anti-idiotype monoclonal antibodies to emicizumab END start-ver=1.4 cd-journal=joma no-vol=122 cd-vols= no-issue=5 article-no= start-page=689 end-page=699 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cytomegalovirus reactivation in patients with large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Chimeric antigen receptor (CAR) T-cell therapy has improved outcomes of relapsed and/or refractory large B-cell lymphoma (r/r LBCL). However, its off-tumor effects result in severe prolonged humoral immune deficiency. Cytomegalovirus (CMV) is a latent virus that can be life-threatening in immunosuppressed patients. In the setting of CAR T-cell therapy, Asian race is a risk factor for clinically significant CMV infection. However, the effect of CAR T-cell therapy on CMV reactivation in Japanese patients remains unclear. Previous reports used polymerase chain reaction (PCR), but we used the pp65 antigenemia assay to retrospectively investigate long-term effects in patients with r/r LBCL. The study included 46 patients. Nine (19.6%) developed CMV reactivation, with a median onset of 13 days. Six of these patients received preemptive therapy, and none developed CMV end-organ disease. Primary refractory disease, grade 2?4 cytokine release syndrome, and high-dose corticosteroids were risk factors for CMV reactivation. Long-term follow-up showed that CMV reactivation rarely occurred later than 28 days post-infusion. Our study using the pp65 antigenemia assay showed a similar incidence of CMV reactivation, onset, and risk factors to those in the previous reports using PCR. en-copyright= kn-copyright= en-aut-name=HayashinoKenta en-aut-sei=Hayashino en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MasunariTaro en-aut-sei=Masunari en-aut-mei=Taro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HashidaRisa en-aut-sei=Hashida en-aut-mei=Risa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OkaSatoshi en-aut-sei=Oka en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraYuki en-aut-sei=Fujiwara en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KamoiChihiro en-aut-sei=Kamoi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=3 en-affil=Department of Hematology, Chugoku Central Hospital kn-affil= affil-num=4 en-affil=Division of Hematology, Ehime Prefectural Central Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Science Center kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=16 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University kn-affil= en-keyword=Cytomegalovirus reactivation kn-keyword=Cytomegalovirus reactivation en-keyword=Large B-cell lymphoma kn-keyword=Large B-cell lymphoma en-keyword=CAR T-cell therapy kn-keyword=CAR T-cell therapy en-keyword=Hypogammaglobulinemia kn-keyword=Hypogammaglobulinemia END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20251019 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impact of methotrexate-dosing regimens for GVHD prophylaxis on clinical outcomes of HLA-matched allogeneic HSCT en-subtitle= kn-subtitle= en-abstract= kn-abstract=Severe graft-versus-host disease (GVHD) remains a major complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT), necessitating optimal immunosuppressive strategies. This retrospective study used data from the Japanese Transplant Registry Unified Management Program to compare three methotrexate (MTX)-dosing regimens for GVHD prophylaxis in patients undergoing human leucocyte antigen (HLA)-matched allo-HSCT: a low-dose 3-day regimen (Ld3:10?mg/m2 on day 1, 7?mg/m2 on days 3 and 6), a low-dose 4-day regimen (Ld4: Ld3 with an additional 7?mg/m2 on day 11) and an original-dose 3-day regimen (Od3: 15?mg/m2 on day 1, 10?mg/m2 on days 3 and 6). Among 2537 analysed patients, Ld3 was the most commonly used regimen. Multivariate analyses showed no significant differences in the cumulative incidence of grade II?IV acute GVHD among regimens. However, Od3 was associated with an increased risk of grade III?IV acute GVHD, and Ld4 was linked to delayed neutrophil engraftment. This study is the first large-scale retrospective analysis of the impact of different MTX-dosing regimens on the outcomes of HLA-matched allo-HSCT, providing valuable insights into optimal MTX-dosing strategies in clinical practice. en-copyright= kn-copyright= en-aut-name=SuzukiTomotaka en-aut-sei=Suzuki en-aut-mei=Tomotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=JoTomoyasu en-aut-sei=Jo en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YoshifujiKota en-aut-sei=Yoshifuji en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTadakazu en-aut-sei=Kondo en-aut-mei=Tadakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishidaTetsuya en-aut-sei=Nishida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OnishiYasushi en-aut-sei=Onishi en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SawaMasashi en-aut-sei=Sawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HasegawaYuta en-aut-sei=Hasegawa en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SerizawaKentaro en-aut-sei=Serizawa en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OtaShuichi en-aut-sei=Ota en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YoshimitsuMakoto en-aut-sei=Yoshimitsu en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=3 en-affil=Department of Hematology, Institute of Science Tokyo kn-affil= affil-num=4 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=5 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome Hospital kn-affil= affil-num=6 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Centre kn-affil= affil-num=7 en-affil=Department of Hematology, Japanese Red Cross Aichi Medical Centre Nagoya Daiichi Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Tohoku University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Haematopoietic Stem Cell Transplantation, National Cancer Centre Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Anjo Kosei Hospital kn-affil= affil-num=12 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Hematology, Sapporo Hokuyu Hospital kn-affil= affil-num=15 en-affil=Department of Hematology, Kanagawa Cancer Centre kn-affil= affil-num=16 en-affil=Department of Hematology and Rheumatology, Graduate School of Medical and Dental Sciences, Kagoshima University kn-affil= affil-num=17 en-affil=Japanese Data Centre for Haematopoietic Cell Transplantation kn-affil= affil-num=18 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= en-keyword=allo-HSCT kn-keyword=allo-HSCT en-keyword=dosing regimens kn-keyword=dosing regimens en-keyword=graft-versus-host disease kn-keyword=graft-versus-host disease en-keyword=GVHD prophylaxis kn-keyword=GVHD prophylaxis en-keyword=methotrexate kn-keyword=methotrexate END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=5 article-no= start-page=e70138 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250902 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Late]Onset?Invasive Aspergillosis With Pituitary Involvement and Dysfunction Following CD19 Chimeric Antigen Receptor T]Cell Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction: Invasive fungal infection (IFI) after chimeric antigen receptor (CAR) T-cell therapy is less common than bacterial and viral infections, but can be fatal once it develops. As most cases occur within 30 days after CAR T-cell infusion, late-onset IFI?particularly mould infection?appears to be under-recognised.
Discussion: We report an illustrative case of pituitary aspergillosis developing as late as one year after CD19 CAR T-cell therapy, highlighting a persistent risk in certain patients with delayed immune reconstitution.
Conclusion: This case underscores the need for continued vigilance and individualised antifungal strategies to prevent IFI beyond the early post-infusion period.
Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission. en-copyright= kn-copyright= en-aut-name=IkedaDaisuke en-aut-sei=Ikeda en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NawadaTomohiro en-aut-sei=Nawada en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShinoharaTakayuki en-aut-sei=Shinohara en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NaganoTomohiro en-aut-sei=Nagano en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KubotaSaya en-aut-sei=Kubota en-aut-mei=Saya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiyamaRyuichiro en-aut-sei=Hiyama en-aut-mei=Ryuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UenoMasaya en-aut-sei=Ueno en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MakitaMasanori en-aut-sei=Makita en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=The Center for Graduate Medical Education, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Fungal Infection, National Institute of Infectious Diseases kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology, Chugoku Central Hospital kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=aspergillosis kn-keyword=aspergillosis en-keyword=CD19 CAR T kn-keyword=CD19 CAR T en-keyword=invasive fungal infection kn-keyword=invasive fungal infection en-keyword=pituitary kn-keyword=pituitary END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=18 article-no= start-page=4640 end-page=4653 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250912 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Refinement of day 28 treatment response criteria for acute GVHD: a collaboration study of the JSTCT and MAGIC en-subtitle= kn-subtitle= en-abstract= kn-abstract=Overall response (OR) that combines complete (CR) and partial responses (PR) is the conventional end point for acute graft-versus-host disease (GVHD) trials. Because PR includes heterogeneous clinical presentations, reclassifying PR could produce a better end point. Patients in the primary treatment cohort from the Japanese Society for Transplantation and Cellular Therapy (JSTCT) were randomly divided into training and validation sets. In the training set, a classification and regression tree algorithm generated day 28 refined response (RR) criteria based on symptoms at treatment and day 28. We then evaluated RR for primary and second-line treatments, using the area under the receiver operating characteristic curve (AUC) and negative predictive value (NPV) for 6-month nonrelapse mortality as performance measures. RR considered patients with grade 0/1 at day 28 without additional treatment as responders. RR for primary treatment produced higher AUCs than OR with small improvement of NPVs in both validation sets: JSTCT (AUC, 0.73 vs 0.69 [P < .001]; NPV, 92.0% vs 89.6% [P < .001]) and the Mount Sinai Acute GVHD International Consortium (MAGIC; AUC, 0.71 vs 0.68 [P = .032]; NPV, 90.9% vs 89.8% [P = .009]). RR for second-line treatment produced similar AUCs but much higher NPVs than OR in both validation sets of JSTCT (AUC, 0.64 vs 0.63 [P = .775]; NPV, 74.5% vs 66.0% [P < .001]) and MAGIC (AUC, 0.67 vs 0.64 [P = .105]; NPV, 86.8% vs 76.1% [P = .004]). Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials. en-copyright= kn-copyright= en-aut-name=AkahoshiYu en-aut-sei=Akahoshi en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InamotoYoshihiro en-aut-sei=Inamoto en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SpyrouNikolaos en-aut-sei=Spyrou en-aut-mei=Nikolaos kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakasoneHideki en-aut-sei=Nakasone en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DinizMarcio A. en-aut-sei=Diniz en-aut-mei=Marcio A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AyukFrancis en-aut-sei=Ayuk en-aut-mei=Francis kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ChoeHannah K. en-aut-sei=Choe en-aut-mei=Hannah K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EtoTetsuya en-aut-sei=Eto en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EtraAaron M. en-aut-sei=Etra en-aut-mei=Aaron M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HexnerElizabeth O. en-aut-sei=Hexner en-aut-mei=Elizabeth O. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HiramotoNobuhiro en-aut-sei=Hiramoto en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HoganWilliam J. en-aut-sei=Hogan en-aut-mei=William J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=HollerErnst en-aut-sei=Holler en-aut-mei=Ernst kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KataokaKeisuke en-aut-sei=Kataoka en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KawakitaToshiro en-aut-sei=Kawakita en-aut-mei=Toshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TanakaTakashi en-aut-sei=Tanaka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=UchidaNaoyuki en-aut-sei=Uchida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=VasovaIngrid en-aut-sei=Vasova en-aut-mei=Ingrid kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=YoshiharaSatoshi en-aut-sei=Yoshihara en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=IshimaruFumihiko en-aut-sei=Ishimaru en-aut-mei=Fumihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ChenYi-Bin en-aut-sei=Chen en-aut-mei=Yi-Bin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=NakamuraRyotaro en-aut-sei=Nakamura en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=FerraraJames L. M. en-aut-sei=Ferrara en-aut-mei=James L. M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=LevineJohn E. en-aut-sei=Levine en-aut-mei=John E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=TeshimaTakanori en-aut-sei=Teshima en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=2 en-affil=Department of Blood and Marrow Transplantation and Cellular Therapy, Fujita Health University School of Medicine kn-affil= affil-num=3 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=4 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=5 en-affil=Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf kn-affil= affil-num=8 en-affil=Division of Hematology, Blood and Marrow Transplantation Program, The Ohio State University Comprehensive Cancer Center kn-affil= affil-num=9 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Hamanomachi Hospital kn-affil= affil-num=11 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=12 en-affil=Department of Medicine and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=13 en-affil=Department of Hematology, Kobe City Medical Center General Hospital kn-affil= affil-num=14 en-affil=Division of Hematology, Mayo Clinic kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Internal Medicine III, University of Regensburg kn-affil= affil-num=16 en-affil=Division of Molecular Oncology, National Cancer Center Research Institute kn-affil= affil-num=17 en-affil=Department of Hematology, National Hospital Organization Kumamoto Medical Center kn-affil= affil-num=18 en-affil=Department of Hematology, Kanagawa Cancer Center kn-affil= affil-num=19 en-affil=Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=20 en-affil=Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital kn-affil= affil-num=21 en-affil=Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-Universit?t Erlangen-N?rnberg and University Hospital Erlangen kn-affil= affil-num=22 en-affil=Department of Hematology, Hyogo Medical University Hospital kn-affil= affil-num=23 en-affil=Technical Department, Japanese Red Cross Blood Service Headquarters kn-affil= affil-num=24 en-affil=Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=25 en-affil=Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital kn-affil= affil-num=26 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=27 en-affil=Department of Hematology and Hematopoietic Cell Transplantation, City of Hope kn-affil= affil-num=28 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=29 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=30 en-affil=Division of Hematology, Jichi Medical University Saitama Medical Center kn-affil= affil-num=31 en-affil=Division of Hematology/Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai kn-affil= affil-num=32 en-affil=Department of Hematology, Hokkaido University Faculty of Medicine and Graduate School of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250908 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficacy of ciclosporin monotherapy in non-severe aplastic anaemia not requiring transfusions: Results from a multicentre phase II study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The efficacy of ciclosporin (CsA) to treat transfusion-independent non-severe aplastic anaemia (TI-NSAA) has not yet been systematically evaluated. We conducted a prospective trial in patients with TI-NSAA treated with CsA monotherapy. CsA (3.5?mg/kg/day) was administered to patients with TI-NSAA aged ?16. The CsA dose was adjusted to maintain a blood CsA level of ?600?ng/mL at 2?h post-administration. Blood cell counts were assessed after 8, 16 and 52?weeks of therapy. Thirty-two evaluable patients from 21 institutions were enrolled. The median age was 63.5 (range: 16?83) years. At 8?weeks, haematological improvement, with increases in haemoglobin (Hb) ?1.5?g/dL (haematological improvement in erythrocytes [HI-E]) and platelet count ?30?~?109/L (haematological improvement in platelets [HI-P]), was observed in 0/25 (0%) and 6/32 (19%) evaluable cases respectively. HI-E and HI-P occurred in 1/25 (4%) and 10/32 (31%) patients at 16?weeks, respectively, and at 52?weeks in 5/25 (20%) and 16/32 (50%) patients respectively. Nine grade 3 adverse events (AEs) occurred in six patients, but there were no grade ?4 AEs. Ten of the 32 patients experienced grade 2 renal toxicity. Low-dose CsA is effective in TI-NSAA patients and demonstrates minimal renal toxicity. However, at least 16?weeks are necessary to adequately evaluate its efficacy. en-copyright= kn-copyright= en-aut-name=IshiyamaKen en-aut-sei=Ishiyama en-aut-mei=Ken kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamazakiMasahide en-aut-sei=Yamazaki en-aut-mei=Masahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaruyamaHiroyuki en-aut-sei=Maruyama en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosonoNaoko en-aut-sei=Hosono en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamaguchiHiroki en-aut-sei=Yamaguchi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TanimotoKazuki en-aut-sei=Tanimoto en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiuraHiroyuki en-aut-sei=Sugiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UsukiKensuke en-aut-sei=Usuki en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshimuraKenichi en-aut-sei=Yoshimura en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OgawaSeishi en-aut-sei=Ogawa en-aut-mei=Seishi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KanakuraYuzuru en-aut-sei=Kanakura en-aut-mei=Yuzuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsumuraItaru en-aut-sei=Matsumura en-aut-mei=Itaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AkashiKoichi en-aut-sei=Akashi en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakaoShinji en-aut-sei=Nakao en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology, Kanazawa University Hospital kn-affil= affil-num=2 en-affil=Department of Internal Medicine, Keiju Medical Center kn-affil= affil-num=3 en-affil=Department of Hematology, Kanazawa University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, University of Fukui Hospital kn-affil= affil-num=5 en-affil=Department of Hematology, Nippon Medical School kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Japanese Red Cross Fukuoka Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Chugoku Central Hospital of Japan Mutual Aid Association of Public School Teachers kn-affil= affil-num=9 en-affil=Department of Hematology, NTT Medical Center Tokyo kn-affil= affil-num=10 en-affil=Department of Biostatistics and Health Data Science, Graduate School of Medical Science, Nagoya City University kn-affil= affil-num=11 en-affil=Department of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University kn-affil= affil-num=12 en-affil=Sumitomo Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Rheumatology, Kindai University Faculty of Medicine kn-affil= affil-num=14 en-affil=Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences kn-affil= affil-num=15 en-affil=Department of Hematology, Kanazawa University Hospital kn-affil= en-keyword=ciclosporin kn-keyword=ciclosporin en-keyword=prospective study kn-keyword=prospective study en-keyword=renal toxicity kn-keyword=renal toxicity en-keyword=transfusion-independent non-severe aplastic anaemia kn-keyword=transfusion-independent non-severe aplastic anaemia END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=6 article-no= start-page=e098532 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Protocol for a multicentre, open-label, dose-escalation phase I/II study evaluating the tolerability, safety, efficacy and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with aggressive natural killer cell leukaemia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Introduction Aggressive natural killer cell leukaemia (ANKL) is a rare form of NK cell lymphoma with a very low incidence and poor prognosis. While multi-agent chemotherapy including L-asparaginase has been used to treat ANKL patients, they often cannot receive adequate chemotherapy at diagnosis due to liver dysfunction. PPMX-T003, a fully human monoclonal antibody targeting the transferrin receptor 1, shows promise in treating ANKL by helping patients recover from fulminant clinical conditions, potentially enabling a transition to chemotherapy. This study aimed to evaluate the tolerability, safety, efficacy, and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with ANKL.
Methods and analysis This multicentre, open-label, dose-escalation phase I/II study will be conducted at nine hospitals in Japan. Patients diagnosed with ANKL (whether as a primary or recurrent disease) and exhibiting abnormal liver function or hepatomegaly due to the primary disease will be included. The primary endpoint is the tolerability and safety of repeated continuous intravenous administration of PPMX-T003 in the first course, based on adverse events and dose-limiting toxicities. PPMX-T003 will be administered as a continuous intravenous infusion every 24?hours for five consecutive days, followed by a 2-day break. Pretreatment will be provided to minimise the risk of infusion-related reactions. Initial doses of PPMX-T003 will be 0.5, 1.0 or 2.0 mg/kg, with subsequent dose increases determined by the Data and Safety Monitoring Committee. The sample size is set at seven participants, with enrolment increased to up to 12 participants if dose-limiting toxicities occur, based on feasibility due to the rarity of ANKL. Descriptive statistics will summarise data according to initial dose, and pharmacokinetic analysis will be conducted based on administered dose.
Ethics and dissemination This study was approved by the institutional review boards at participating hospitals. The results will be disseminated in peer-reviewed journals.
Trial registration number jRCT2061230008 (jRCT); NCT05863234 (ClinicalTrials.gov). en-copyright= kn-copyright= en-aut-name=FukuharaNoriko en-aut-sei=Fukuhara en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OnizukaMakoto en-aut-sei=Onizuka en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KandaJunya en-aut-sei=Kanda en-aut-mei=Junya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatoKoji en-aut-sei=Kato en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AndoKiyoshi en-aut-sei=Ando en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Hematology, Tohoku University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Tokai University School of Medicine Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Hematology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=6 en-affil=Department of Hematology, Hiroshima University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=121 cd-vols= no-issue=2 article-no= start-page=232 end-page=243 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20241216 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Outcomes of allogeneic SCT versus tisagenlecleucel in patients with R/R LBCL and poor prognostic factors en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study investigated the efficacy of tisagenlecleucel (tisa-cel) and allogeneic hematopoietic stem cell transplantation (allo-SCT) for patients with relapsed and/or refractory (r/r) large B-cell lymphoma (LBCL) with poor prognostic factors, defined as performance status (PS)???2, multiple extranodal lesions (EN), chemorefractory disease, or higher lactate dehydrogenase (LDH). Overall, the allo-SCT group demonstrated worse progression-free survival (PFS), higher non-relapse mortality, and a similar relapse/progression rate. Notably, the tisa-cel group showed better PFS than the allo-SCT group among patients with chemorefractory disease (3.2 vs. 2.0 months, p?=?0.092) or higher LDH (4.0 vs. 2.0 months, p =?0.018), whereas PFS in the two cellular therapy groups was similar among those with PS???2 or multiple EN. Survival time after relapse post-cellular therapy in patients with poor prognostic factors was 1.6 with allo-SCT and 4.6 months with tisa-cel. These findings were confirmed in a propensity score matching cohort. In conclusion, tisa-cel resulted in better survival than allo-SCT in patients with poor prognostic factors. However, patients who relapsed post-cellular therapy had dismal outcomes regardless of therapy. Further strategies are warranted to improve outcomes in these patients. en-copyright= kn-copyright= en-aut-name=HayashinoKenta en-aut-sei=Hayashino en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KamoiChihiro en-aut-sei=Kamoi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital, Okayama University kn-affil= en-keyword=Large B-cell lymphoma kn-keyword=Large B-cell lymphoma en-keyword=Allogeneic hematopoietic stem cell transplantation kn-keyword=Allogeneic hematopoietic stem cell transplantation en-keyword=CAR-T cell therapy kn-keyword=CAR-T cell therapy en-keyword=Tisagenlecleucel kn-keyword=Tisagenlecleucel en-keyword=Poor prognostic factors kn-keyword=Poor prognostic factors END start-ver=1.4 cd-journal=joma no-vol=31 cd-vols= no-issue=6 article-no= start-page=388.e1 end-page=388.e14 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202506 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical effects of granulocyte colony-stimulating factor administration and the timing of its initiation on allogeneic hematopoietic cell transplantation outcomes for myelodysplastic syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=Granulocyte colony-stimulating factor (G-CSF) accelerates neutrophil recovery after allogeneic hematopoietic cell transplantation (HCT). However, the optimal use of G-CSF and the timing of its initiation after allogeneic HCT for myelodysplastic syndrome (MDS) according to graft type have not been determined. This retrospective study aimed to investigate the effects of using G-CSF administration and the timing of its initiation on transplant outcomes in adult patients with MDS undergoing allogeneic HCT. Using Japanese registry data, we retrospectively investigated the effects of G-CSF administration and the timing of its initiation on transplant outcomes among 4140 adults with MDS after bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), or single-unit cord blood transplantation (CBT) between 2013 and 2022. Multivariate analysis showed that early (days 0 to 4) and late (days 5 to 10) G-CSF administration significantly accelerated neutrophil recovery compared with no G-CSF administration following BMT, PBSCT, and CBT, but there was no benefit of early G-CSF initiation for early neutrophilic recovery regardless of graft type. Late G-CSF initiation was significantly associated with a higher risk of overall chronic GVHD following PBSCT (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.18 to 2.24; P = .002) and CBT (HR, 2.09; 95% CI, 1.21 to 3.60; P = .007) compared with no G-CSF administration. Late G-CSF initiation significantly improved OS compared with no G-CSF administration only following PBSCT (HR, 0.74; 95% CI, 0.58 to 0.94; P = .015). However, G-CSF administration and the timing of its initiation did not affect acute GVHD, relapse, or non-relapse mortality, irrespective of graft type. These results suggest that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT, but increased risk of overall chronic GVHD after PBSCT and CBT. However, the effect of early and late G-CSF initiation on transplant outcomes needs further study in adult patients with MDS. en-copyright= kn-copyright= en-aut-name=KonumaTakaaki en-aut-sei=Konuma en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiokaMachiko en-aut-sei=Fujioka en-aut-mei=Machiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FuseKyoko en-aut-sei=Fuse en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HosoiHiroki en-aut-sei=Hosoi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MasamotoYosuke en-aut-sei=Masamoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DokiNoriko en-aut-sei=Doki en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UchidaNaoyuki en-aut-sei=Uchida en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaMasatsugu en-aut-sei=Tanaka en-aut-mei=Masatsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SawaMasashi en-aut-sei=Sawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishidaTetsuya en-aut-sei=Nishida en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshikawaJun en-aut-sei=Ishikawa en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakamaeHirohisa en-aut-sei=Nakamae en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=HasegawaYuta en-aut-sei=Hasegawa en-aut-mei=Yuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OnizukaMakoto en-aut-sei=Onizuka en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MaedaTakeshi en-aut-sei=Maeda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FukudaTakahiro en-aut-sei=Fukuda en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawamuraKoji en-aut-sei=Kawamura en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KandaYoshinobu en-aut-sei=Kanda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhbikiMarie en-aut-sei=Ohbiki en-aut-mei=Marie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=AtsutaYoshiko en-aut-sei=Atsuta en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ItonagaHidehiro en-aut-sei=Itonaga en-aut-mei=Hidehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= affil-num=1 en-affil=Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Hematology, Sasebo City General Hospital kn-affil= affil-num=3 en-affil=Faculty of Medicine, Department of Hematology, Endocrinology and Metabolism, Niigata University kn-affil= affil-num=4 en-affil=Department of Hematology/Oncology, Wakayama Medical University kn-affil= affil-num=5 en-affil=Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital kn-affil= affil-num=6 en-affil=Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital kn-affil= affil-num=7 en-affil=Department of Hematology, Toranomon Hospital kn-affil= affil-num=8 en-affil=Department of Hematology, Kanagawa Cancer Center kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Anjo Kosei Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital kn-affil= affil-num=11 en-affil=Department of Hematology, Osaka International Cancer Institute kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Osaka Metropolitan University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Hematology, Hokkaido University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Tokai University School of Medicine kn-affil= affil-num=16 en-affil=Department of Hematology and oncology, Kurashiki Central Hospital kn-affil= affil-num=17 en-affil=Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital kn-affil= affil-num=18 en-affil=Department of Hematology, Tottori University Hospital kn-affil= affil-num=19 en-affil=Division of Hematology, Jichi Medical University kn-affil= affil-num=20 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=21 en-affil=Japanese Data Center for Hematopoietic Cell Transplantation kn-affil= affil-num=22 en-affil=Transfusion and Cell Therapy Unit, Nagasaki University Hospital kn-affil= en-keyword=Granulocyte colony-stimulating factor kn-keyword=Granulocyte colony-stimulating factor en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Bone marrow transplantation kn-keyword=Bone marrow transplantation en-keyword=Peripheral blood stem cell transplantation kn-keyword=Peripheral blood stem cell transplantation en-keyword=Cord blood transplantation kn-keyword=Cord blood transplantation en-keyword=Myelodysplastic syndrome kn-keyword=Myelodysplastic syndrome END start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=4 article-no= start-page=e82348 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250416 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bilateral Scleritis and Neutrophilic Dermatosis With Cytogenetic Chromosomal Aberrancy Related to Pyoderma Gangrenosum: A Case Report of a 20-Year Follow-Up en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pyoderma gangrenosum is a non-infectious autoimmune disease with skin plaques and ulcers in the entity of neutrophilic dermatosis and may have a background of myelodysplastic syndromes. This study reported a 20-year follow-up of a patient with pyoderma gangrenosum and scleritis who showed chromosomal aberrancy from the initial phase and later in the course developed thrombocythemia. A 51-year-old man presented with widespread indurated erythematous plaques with scaling and pustules on the forehead, bilateral eyelids, and nasal bridge, in addition to nodular scleritis in the left eye and ulcer formation of the plaques in the lower legs. Skin biopsy revealed massive dermal infiltration mainly with neutrophils in the absence of neutrophilic vasculitis. Suspected of myelodysplastic syndromes, bone marrow biopsy was normal, while chromosomal aberrancy, 46, XY, del (20) (q11q13.3), was detected. In the diagnosis of neutrophilic dermatosis, probably of pyoderma gangrenosum, he began to have oral prednisolone 20 mg daily and colchicine 1 mg daily, leading to the subsidence of skin lesions. Four months later, he developed nodular scleritis in the right eye and began to use topical 0.1% betamethasone in both eyes. He was stable with only prednisolone 12.5 mg daily until the age of 55.5 years, when he showed an increase of serum lactate dehydrogenase. The bone marrow aspirate disclosed neither blast cell increase nor atypical cells. The same chromosomal aberrancy was repeatedly detected. One year later, he developed breathing difficulty and underwent tracheostomy. Laryngeal lesion biopsy disclosed squamous cell papilloma with human papillomavirus-6. At 60 years old, he showed marginal corneal infiltration in the left eye, and at 61 years old, hypopyon in the right eye. Platelets tended to increase up to 1000 ~ 103/?L, and bone marrow examinations were recommended but refused by the patient. At the latest follow-up at 71 years old, he was ambulatory in health and stable with a tracheostomy cannula. In conclusion, pyoderma gangrenosum with scleritis occurred in an undetermined hematological malignancy with chromosomal aberrancy. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ObikaMikako en-aut-sei=Obika en-aut-mei=Mikako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OmichiRyotaro en-aut-sei=Omichi en-aut-mei=Ryotaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of General Internal Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=corneal infiltration kn-keyword=corneal infiltration en-keyword=hypopyon kn-keyword=hypopyon en-keyword=myelodysplastic syndromes kn-keyword=myelodysplastic syndromes en-keyword=neutrophilic dermatosis kn-keyword=neutrophilic dermatosis en-keyword=peripheral keratitis kn-keyword=peripheral keratitis en-keyword=pyoderma gangrenosum kn-keyword=pyoderma gangrenosum en-keyword=scleritis kn-keyword=scleritis en-keyword=sweet syndrome kn-keyword=sweet syndrome END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250224 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD en-subtitle= kn-subtitle= en-abstract= kn-abstract=Therapies that effectively suppress graft-versus-host disease (GVHD) without compromising graft-versus-leukemia/lymphoma (GVL) effects is important in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic malignancies. Geranylgeranylacetone (GGA) is a main component of teprenone, a gastric mucosal protectant commonly used in clinical practice. In preclinical models, GGA suppresses proinflammatory cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor- (TNF-), which are associated with GVHD as well as induces thioredoxin-1 (Trx-1), which suppresses GVHD while maintaining GVL effects. Here, we investigated whether the addition of teprenone to standard GVHD prophylaxis could reduce the cumulative incidence of severe acute GVHD (aGVHD) without attenuating GVL effects. This open-label, randomized clinical trial enrolled 40 patients (21 control and 19 teprenone group) who received allo-HSCT between May 2022 and February 2023 in our institution. Patients in the teprenone group received 50 mg of teprenone orally thrice daily for 21 days from the initiation of the conditioning regimen. The cumulative incidence of severe aGVHD by day 100 after allo-HSCT was not significantly different in the two groups (27.9 vs. 16.1%, p?=?0.25). The exploratory studies revealed no obvious changes in Trx-1 levels, but the alternations from baseline in IL-1 and TNF- levels at day 28 after allo-HSCT tended to be lower in the teprenone group. In conclusion, we could not demonstrate that teprenone significantly prevented the development of severe aGVHD. Discrepancy with preclinical model suggests that appropriate dose of teprenone may be necessary to induce the expression of antioxidant enzymes that suppress severe aGVHD. Clinical Trial Registration number:jRCTs 061210072. en-copyright= kn-copyright= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KamoiChihiro en-aut-sei=Kamoi en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoAkira en-aut-sei=Yamamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatric Acute Diseases, Okayama University Academic Field of Medicine Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=Allogeneic hematopoietic stem cell transplantation kn-keyword=Allogeneic hematopoietic stem cell transplantation en-keyword=Graft-versus-host disease kn-keyword=Graft-versus-host disease en-keyword=Teprenone kn-keyword=Teprenone en-keyword=Oxidative stress kn-keyword=Oxidative stress en-keyword=Interleukin-33 kn-keyword=Interleukin-33 END start-ver=1.4 cd-journal=joma no-vol=145 cd-vols= no-issue=8 article-no= start-page=881 end-page=896 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250220 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD. en-copyright= kn-copyright= en-aut-name=KambaraYui en-aut-sei=Kambara en-aut-mei=Yui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoAkira en-aut-sei=Yamamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=GotohKazuyoshi en-aut-sei=Gotoh en-aut-mei=Kazuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsujiShuma en-aut-sei=Tsuji en-aut-mei=Shuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KunihiroMari en-aut-sei=Kunihiro en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OyamaTadashi en-aut-sei=Oyama en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatoAyame en-aut-sei=Sato en-aut-mei=Ayame kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=PeltierDaniel en-aut-sei=Peltier en-aut-mei=Daniel kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SeikeKeisuke en-aut-sei=Seike en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=SogaYoshihiko en-aut-sei=Soga en-aut-mei=Yoshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=ReddyPavan en-aut-sei=Reddy en-aut-mei=Pavan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YoshinobuMaeda en-aut-sei=Yoshinobu en-aut-mei=Maeda kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Medical School kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences kn-affil= affil-num=5 en-affil=Department of Microbiology and Genetics, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Simon Cancer Center, Indiana University School of Medicine kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=17 en-affil=Division of Blood Transfusion, Okayama University Hospital kn-affil= affil-num=18 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Division of Hospital Dentistry, Okayama University Hospital kn-affil= affil-num=20 en-affil=Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine kn-affil= affil-num=21 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=4 article-no= start-page=810 end-page=814 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240619 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Combination of reduced post-transplant cyclophosphamide and early tacrolimus initiation increases the incidence of chronic graft-versus-host disease in human leukocyte antigen-haploidentical peripheral blood stem-cell transplantation en-subtitle= kn-subtitle= en-abstract= kn-abstract=We evaluated the clinical impacts of the concurrent modification of post-transplant cyclophosphamide (PTCy) dose and tacrolimus (Tac)-initiation timing in 61 patients with human leukocyte antigen-haploidentical transplantation. Reduced-dose PTCy (80 mg/kg) was associated with a higher incidence of moderate-to-severe chronic graft-versus-host disease (GVHD) than standard-dose PTCy (100 mg/kg) (35.0% vs. 26.6%, p = 0.053). Notably, early-initiation Tac (day -1) increased moderate-to-severe chronic GVHD than standard-initiation Tac (day 5) in the reduced-dose PTCy group (p = 0.032), whereas Tac-initiation timing did not impact chronic GVHD in the standard-dose PTCy group. These data indicate that the combination of reduced-dose PTCy and early-initiation Tac can amplify chronic GVHD. en-copyright= kn-copyright= en-aut-name=TeraoToshiki en-aut-sei=Terao en-aut-mei=Toshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakamuraMakoto en-aut-sei=Nakamura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakasukaHiroki en-aut-sei=Takasuka en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=chronic GVHD kn-keyword=chronic GVHD en-keyword=haploidentical kn-keyword=haploidentical en-keyword=hematopoietic stem-cell transplantation kn-keyword=hematopoietic stem-cell transplantation en-keyword=PTCy kn-keyword=PTCy en-keyword=tacrolimus kn-keyword=tacrolimus END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=10 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231031 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance.
Methods: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC.
Results: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation.
Conclusions: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-na?ve EGFR-mutant NSCLC. en-copyright= kn-copyright= en-aut-name=HaraNaofumi en-aut-sei=Hara en-aut-mei=Naofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanoHirohisa en-aut-sei=Kano en-aut-mei=Hirohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AndoChihiro en-aut-sei=Ando en-aut-mei=Chihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MoritaAyako en-aut-sei=Morita en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiTatsuya en-aut-sei=Nishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OkawaSachi en-aut-sei=Okawa en-aut-mei=Sachi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakasukaTakamasa en-aut-sei=Nakasuka en-aut-mei=Takamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HirabaeAtsuko en-aut-sei=Hirabae en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AbeMasaya en-aut-sei=Abe en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiMasanori en-aut-sei=Fujii en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=KuboToshio en-aut-sei=Kubo en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OhashiKadoaki en-aut-sei=Ohashi en-aut-mei=Kadoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=HottaKatsuyuki en-aut-sei=Hotta en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=17 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=18 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=19 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=Epidermal growth factor receptor (EGFR) kn-keyword=Epidermal growth factor receptor (EGFR) en-keyword=non-small cell lung cancer (NSCLC) kn-keyword=non-small cell lung cancer (NSCLC) en-keyword=cell cycle kn-keyword=cell cycle en-keyword=CDK4/6 inhibitor kn-keyword=CDK4/6 inhibitor END start-ver=1.4 cd-journal=joma no-vol=53 cd-vols= no-issue=7 article-no= start-page=595 end-page=603 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Venetoclax plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy: an expanded access study in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: In a Phase 3 international clinical trial (VIALE-C), venetoclax plus low-dose cytarabine improved the response rate and overall survival versus placebo plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia who were ineligible for intensive chemotherapy. After the enrollment period of VIALE-C ended, we conducted an expanded access study to provide preapproval access to venetoclax in combination with low-dose cytarabine in Japan.
Methods: Previously, untreated patients with acute myeloid leukemia who were ineligible for intensive chemotherapy were enrolled according to the VIALE-C criteria. Patients received venetoclax (600 mg, Days 1?28, 4-day ramp-up in Cycle 1) in 28-day cycles and low-dose cytarabine (20 mg/m2, Days 1?10). All patients took tumor lysis syndrome prophylactic agents and hydration. Safety endpoints were assessed.
Results: Fourteen patients were enrolled in this study. The median age was 77.5 years (range = 61?84), with 78.6% over 75 years old. The most common grade ? 3 treatment-emergent adverse event was neutropenia (57.1%). Febrile neutropenia was the most frequent serious adverse event (21.4%). One patient developed treatment-related acute kidney injury, leading to discontinuation of treatment. Two patients died because of cardiac failure and disease progression that were judged not related to study treatment. No patients developed tumor lysis syndrome.
Conclusions: The safety outcomes were similar to those in VIALE-C without new safety signals and were well managed with standard medical care. In clinical practice, more patients with severe background disease are expected, in comparison with in VIALE-C, suggesting that it is important to carefully manage and prevent adverse events. en-copyright= kn-copyright= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AndoJun en-aut-sei=Ando en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakadaSatoru en-aut-sei=Takada en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YoshidaChikashi en-aut-sei=Yoshida en-aut-mei=Chikashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UsukiKensuke en-aut-sei=Usuki en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShinagawaAtsushi en-aut-sei=Shinagawa en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IshizawaKenichi en-aut-sei=Ishizawa en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoToshihiro en-aut-sei=Miyamoto en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IidaHiroatsu en-aut-sei=Iida en-aut-mei=Hiroatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=DobashiNobuaki en-aut-sei=Dobashi en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OkuboSumiko en-aut-sei=Okubo en-aut-mei=Sumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HondaHideyuki en-aut-sei=Honda en-aut-mei=Hideyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=SoshinTomomi en-aut-sei=Soshin en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=NishimuraYasuko en-aut-sei=Nishimura en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TsutsuiAtsuko en-aut-sei=Tsutsui en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MukaiHarumi en-aut-sei=Mukai en-aut-mei=Harumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YamamotoKazuhito en-aut-sei=Yamamoto en-aut-mei=Kazuhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology, School of Medicine, Juntendo University kn-affil= affil-num=3 en-affil=Leukemia Research Center, Gunma Saiseikai Maebashi Hospital kn-affil= affil-num=4 en-affil=Department of Hematology, National Hospital Organization Mito Medical Center kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Department of Internal Medicine, Hitachi General Hospital kn-affil= affil-num=7 en-affil=Department of Internal Medicine III, Yamagata University Faculty of Medicine kn-affil= affil-num=8 en-affil=Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=10 en-affil=Division of Clinical Oncology/Hematology, The Jikei University Daisan Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Cell Therapy, AbbVie GK kn-affil= affil-num=12 en-affil=Department of Hematology and Cell Therapy, AbbVie GK kn-affil= affil-num=13 en-affil=Department of Hematology and Cell Therapy, AbbVie GK kn-affil= affil-num=14 en-affil=Department of Hematology and Cell Therapy, AbbVie GK kn-affil= affil-num=15 en-affil=Department of Hematology and Cell Therapy, AbbVie GK kn-affil= affil-num=16 en-affil=Department of Hematology and Cell Therapy, Abbvie Inc. kn-affil= affil-num=17 en-affil=Department of Hematology and Cell Therapy, Aichi Cancer Center kn-affil= en-keyword=acute myeloid leukemia kn-keyword=acute myeloid leukemia en-keyword=venetoclax kn-keyword=venetoclax en-keyword=low-dose cytarabine kn-keyword=low-dose cytarabine en-keyword=expanded access study kn-keyword=expanded access study en-keyword=tumor lysis syndrome kn-keyword=tumor lysis syndrome END start-ver=1.4 cd-journal=joma no-vol=115 cd-vols= no-issue=4 article-no= start-page=1317 end-page=1332 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240126 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Antitumor activity of -pinene in T-cell tumors en-subtitle= kn-subtitle= en-abstract= kn-abstract=T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeu-tic agents have been developed, their therapeutic effects are suboptimal. - Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic ma-lignancies. This report provides a comprehensive analysis of the potential benefits of using - pinene as an antitumor agent for the treatment of T-cell tumors. We found that - pinene inhibited the proliferation of hematologic malignancies, especially in T- cell tumor cell lines EL-4 and Molt-4, induced mitochondrial dysfunction and re-active oxygen species accumulation, and inhibited NF-B p65 translocation into the nucleus, leading to robust apoptosis in EL-4 cells. Collectively, these findings suggest that - pinene has potential as a therapeutic agent for T-cell malignancies, and further investigation is warranted. en-copyright= kn-copyright= en-aut-name=AbeMasaya en-aut-sei=Abe en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimuraMaiko en-aut-sei=Kimura en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukuiChie en-aut-sei=Fukui en-aut-mei=Chie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamadaDaisuke en-aut-sei=Yamada en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WangZiyi en-aut-sei=Wang en-aut-mei=Ziyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MiyakeMasayuki en-aut-sei=Miyake en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaradaTakeshi en-aut-sei=Takarada en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OnoMitsuaki en-aut-sei=Ono en-aut-mei=Mitsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AoeMichinori en-aut-sei=Aoe en-aut-mei=Michinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsudaMasayuki en-aut-sei=Matsuda en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MoriyamaTakashi en-aut-sei=Moriyama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatsumuraAkifumi en-aut-sei=Matsumura en-aut-mei=Akifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Hematology, Department of Medicine, Kobe University Hospital kn-affil= affil-num=5 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Division of Medical Support, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Division of Medical Support, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=alpha-pinene kn-keyword=alpha-pinene en-keyword=apoptosis kn-keyword=apoptosis en-keyword=hematologic malignancies kn-keyword=hematologic malignancies en-keyword=lymphoblastic leukemia, acute, T-cell kn-keyword=lymphoblastic leukemia, acute, T-cell en-keyword=T-cell lymphoma kn-keyword=T-cell lymphoma END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=24 article-no= start-page=7459 end-page=7470 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231214 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Distribution and clinical impact of molecular subtypes with dark zone signature of DLBCL in a Japanese real-world study en-subtitle= kn-subtitle= en-abstract= kn-abstract=The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone (DZ) that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, which include the DZ signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a data set from the cohort of British Columbia Cancer (BCC) (n = 804). Through the 1050 patient samples on which DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to have germinal center B-cell?like (GCB) DLBCL, activated B-cell?like (ABC) DLBCL, and DZsig-positive (DZsigpos) DLBCL, respectively, with the highest prevalence of ABC-DLBCL, differing significantly from the BCC result (P < .001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with 2-year overall survival rates of 88%, 75%, and 66%, respectively (P < .0001), with patients with DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes after rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all, P < .05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas. en-copyright= kn-copyright= en-aut-name=UrataTomohiro en-aut-sei=Urata en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NaoiYusuke en-aut-sei=Naoi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JiangAixiang en-aut-sei=Jiang en-aut-mei=Aixiang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BoyleMerrill en-aut-sei=Boyle en-aut-mei=Merrill kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SunamiKazutaka en-aut-sei=Sunami en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ImaiToshi en-aut-sei=Imai en-aut-mei=Toshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NawaYuichiro en-aut-sei=Nawa en-aut-mei=Yuichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HiramatsuYasushi en-aut-sei=Hiramatsu en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoKazuhiko en-aut-sei=Yamamoto en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiiSoichiro en-aut-sei=Fujii en-aut-mei=Soichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YoshidaIsao en-aut-sei=Yoshida en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YanoTomofumi en-aut-sei=Yano en-aut-mei=Tomofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ChijimatsuRyota en-aut-sei=Chijimatsu en-aut-mei=Ryota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MurakamiHiroyuki en-aut-sei=Murakami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IkeuchiKazuhiro en-aut-sei=Ikeuchi en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TaniKatsuma en-aut-sei=Tani en-aut-mei=Katsuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UjiieHideki en-aut-sei=Ujiie en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=InoueHirofumi en-aut-sei=Inoue en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamamotoAkira en-aut-sei=Yamamoto en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=SawadaKeisuke en-aut-sei=Sawada en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=MomoseShuji en-aut-sei=Momose en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=TamaruJun-ichi en-aut-sei=Tamaru en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=NishikoriAsami en-aut-sei=Nishikori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=ScottDavid W. en-aut-sei=Scott en-aut-mei=David W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=British Columbia Cancer, Centre for Lymphoid Cancer kn-affil= affil-num=4 en-affil=British Columbia Cancer, Centre for Lymphoid Cancer kn-affil= affil-num=5 en-affil=Department of Hematology, NHO Okayama Medical Center kn-affil= affil-num=6 en-affil=Department of Hematology and Blood Transfusion, Kochi Health Sciences Center kn-affil= affil-num=7 en-affil=Division of Hematology, Ehime Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama City Hospital kn-affil= affil-num=10 en-affil=Department of Hematology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=11 en-affil=Department of Hematologic Oncology, NHO Shikoku Cancer Center kn-affil= affil-num=12 en-affil=Department of Internal Medicine, Okayama Rosai Hospital kn-affil= affil-num=13 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=19 en-affil=Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=20 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=22 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=23 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=24 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=25 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=26 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=27 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=28 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=29 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=30 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=31 en-affil=Department of Pathology, Saitama Medical Center, Saitama Medical University kn-affil= affil-num=32 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=33 en-affil=Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=34 en-affil=Department of Pathology, Okayama University kn-affil= affil-num=35 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=36 en-affil=British Columbia Cancer, Centre for Lymphoid Cancer kn-affil= affil-num=37 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=7 article-no= start-page=1344 end-page=1353 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230609 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Granulocyte transfusion therapy is a rational therapeutic option for patients with prolonged, severe neutropenia. Although high molecular weight hydroxyethyl starch (hHES) facilitates the separation of red blood cells during granulocyte collection, renal dysfunction has been noted as a potential side effect. HES130/0.4 (Voluven?) is a medium molecular weight HES (mHES) with superior safety profiles compared to hHES. Although HES130/0.4 is reportedly effective in the collection of granulocytes, we lack studies comparing the efficiency of granulocyte collection using HES130/0.4 and hHES.
Study Design and Methods: We retrospectively collected the data from 60 consecutive apheresis procedures performed on 40 healthy donors at the Okayama University Hospital between July 2013 and December 2021. All procedures were performed using the Spectra Optia system. Based on the HES130/0.4 concentration in the separation chamber, granulocyte collection methods using HES130/0.4 were classified into m0.46, m0.44, m0.37, and m0.8 groups. We used HES130/0.4 and hHES groups to compare the various sample collection methods.
Results: The median granulocyte collection efficiency (CE) was approximately 24.0% and 28.1% in the m0.8 and hHES groups, respectively, which were significantly higher than those in the m0.46, m0.44, and m0.37 groups. One month following granulocyte collection with HES130/0.4, no significant changes were observed in serum creatinine levels compared to those before the donation.
Conclusion: Therefore, we propose a granulocyte collection approach employing HES130/0.4, which is comparable to the use of hHES in terms of the granulocyte CE. A high concentration of HES130/0.4 in the separation chamber was considered crucial for granulocyte collection. en-copyright= kn-copyright= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SumiiYuichi en-aut-sei=Sumii en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UrataTomohiro en-aut-sei=Urata en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimuraMaiko en-aut-sei=Kimura en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsudaMasayuki en-aut-sei=Matsuda en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IkegawaShuntaro en-aut-sei=Ikegawa en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WashioKana en-aut-sei=Washio en-aut-mei=Kana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MatsuokaKen]ichi en-aut-sei=Matsuoka en-aut-mei=Ken]ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=OtsukaFumio en-aut-sei=Otsuka en-aut-mei=Fumio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Division of Transfusion, Okayama University Hospital kn-affil= affil-num=2 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=3 en-affil=Division of Transfusion, Okayama University Hospital kn-affil= affil-num=4 en-affil=Division of Transfusion, Okayama University Hospital kn-affil= affil-num=5 en-affil=Division of Transfusion, Okayama University Hospital kn-affil= affil-num=6 en-affil=Division of Transfusion, Okayama University Hospital kn-affil= affil-num=7 en-affil=Division of Transfusion, Okayama University Hospital kn-affil= affil-num=8 en-affil=Division of Transfusion, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics/Pediatric Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=16 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=blood center operations kn-keyword=blood center operations en-keyword=cellular therapy kn-keyword=cellular therapy en-keyword=therapeutic apheresis kn-keyword=therapeutic apheresis END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=8 article-no= start-page=e162180 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230424 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hematopoietic stem cell-derived Tregs are essential for maintaining favorable B cell lymphopoiesis following posttransplant cyclophosphamide en-subtitle= kn-subtitle= en-abstract= kn-abstract=Posttransplant cyclophosphamide (PTCy) is associated with a low incidence of chronic graft -versus-host disease (cGVHD) following hematopoietic stem cell (HSC) transplantation. Previous studies have shown the important roles of B cell immunity in cGVHD development. Here, we investigated the long-term reconstitution of B lymphopoiesis after PTCy using murine models. We first demonstrated that the immune homeostatic abnormality leading to cGVHD is characterized by an initial increase in effector T cells in the bone marrow and subsequent B and Treg cytopenia. PTCy, but not cyclosporine A or rapamycin, inhibits the initial alloreactive T cell response, which restores intra-bone marrow B lymphogenesis with a concomitant vigorous increase in Tregs. This leads to profound changes in posttransplant B cell homeostasis, including decreased B cell activating factors, increased transitional and regulatory B cells, and decreased germinal center B cells. To identify the cells responsible for PTCy-induced B cell tolerance, we selectively depleted Treg populations that were graft or HSC derived using DEREG mice. Deletion of either Treg population without PTCy resulted in critical B cytopenia. PTCy rescued B lymphopoiesis from graft-derived Treg deletion. In contrast, the negative effect of HSC-derived Treg deletion could not be overcome by PTCy, indicating that HSC-derived Tregs are essential for maintaining favorable B lymphopoiesis following PTCy. These findings define the mechanisms by which PTCy restores homeostasis of the B cell lineage and reestablishes immune tolerance. en-copyright= kn-copyright= en-aut-name=SumiiYuichi en-aut-sei=Sumii en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkegawaShuntaro en-aut-sei=Ikegawa en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukumiTakuya en-aut-sei=Fukumi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwamotoMiki en-aut-sei=Iwamoto en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishimuraMidori Filiz en-aut-sei=Nishimura en-aut-mei=Midori Filiz kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugiuraHiroyuki en-aut-sei=Sugiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SandoYasuhisa en-aut-sei=Sando en-aut-mei=Yasuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakamuraMakoto en-aut-sei=Nakamura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MeguriYusuke en-aut-sei=Meguri en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsushitaTakashi en-aut-sei=Matsushita en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TanimineNaoki en-aut-sei=Tanimine en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KimuraMaiko en-aut-sei=Kimura en-aut-mei=Maiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Dermatology, Faculty of Medicine, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University kn-affil= affil-num=12 en-affil=Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University kn-affil= affil-num=13 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=15 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=15 cd-vols= no-issue=3 article-no= start-page=974 end-page=979 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Sequential Combination of FLAM and Venetoclax plus Azacitidine to Bridge to Cord Blood Transplantation in a Patient with Primary Induction Failure Acute Myeloid Leukemia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Venetoclax (VEN) is an oral B-cell lymphoma-2 (BCL-2) inhibitor that has been widely used to treat various hematological disorders. Recent studies have demonstrated that VEN in combination with fludarabine-enhanced high-dose cytarabine (FLA) is effective for treating relapsed or refractory acute myeloid leukemia (AML). In the combination therapy, salvage chemotherapy and VEN are basically concurrently administrated; however, further optimization may enable the treatment to apply to larger numbers of patients with various clinical backgrounds. Here, we describe a case of refractory AML treated with a sequential combination of the intensive chemotherapy (fludarabine, cytarabine, and mitoxantrone; FLAM) and VEN/AZA to bridge to an unrelated cord blood transplantation (uCBT). By continuously adding VEN/AZA after FLAM, the patient achieved morphologic leukemia free state with only minor toxicities. Blood cell counts did not recover until the time of transplantation because of the deep myelosuppression caused by the treatment sequence, but the infection risk was safely managed during this period. After engraftment, maintenance therapy with VEN/AZA was performed, and the patient has survived without disease recurrence for over 9 months after transplantation. Our case suggests that bridging therapy with VEN and AZA from the time of the last chemotherapy to allogeneic transplantation may provide an effective and tolerable treatment strategy for refractory AML. Further studies of larger numbers of cases are needed to validate the effectiveness of this treatment. en-copyright= kn-copyright= en-aut-name=MurakamiHiroyuki en-aut-sei=Murakami en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AsanoTakeru en-aut-sei=Asano en-aut-mei=Takeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriyamaTakashi en-aut-sei=Moriyama en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsumuraAkifumi en-aut-sei=Matsumura en-aut-mei=Akifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TojiTomohiro en-aut-sei=Toji en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=Refractory acute myeloid leukemia kn-keyword=Refractory acute myeloid leukemia en-keyword=Transplant kn-keyword=Transplant en-keyword=B-cell lymphoma-2 kn-keyword=B-cell lymphoma-2 en-keyword=Azacitidine kn-keyword=Azacitidine en-keyword=Venetoclax kn-keyword=Venetoclax END start-ver=1.4 cd-journal=joma no-vol=67 cd-vols= no-issue=6 article-no= start-page=654 end-page=665 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202212 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Neuropeptide Y Antagonizes Development of Pulmonary Fibrosis through IL-1 Inhibition en-subtitle= kn-subtitle= en-abstract= kn-abstract=Neuropeptide Y (NPY), a 36 amino acid residue polypeptide distributed throughout the nervous system, acts on various immune cells in many organs, including the respiratory system. However, little is known about its role in the pathogenesis of pulmonary fibrosis. This study was performed to determine the effects of NPY on pulmonary fibrosis. NPY-deficient and wild-type mice were intratracheally administered bleomycin. Inflammatory cells, cytokine concentrations, and morphological morphometry of the lungs were analyzed. Serum NPY concentrations were also measured in patients with idiopathic pulmonary fibrosis and healthy control subjects. NPY-deficient mice exhibited significantly enhanced pulmonary fibrosis and higher IL-1 beta concentrations in the lungs compared with wild-type mice. Exogenous NPY treatment suppressed the development of bleomycin-induced lung fibrosis and decreased IL-1 beta concentrations in the lungs. Moreover, IL-1 beta neutralization in NPY-deficient mice attenuated the fibrotic changes. NPY decreased IL-1 beta release, and Y1 receptor antagonists inhibited IL-1 beta release and induced epithelial-mesenchymal transition in human alveolar epithelial cells. Patients with idiopathic pulmonary fibrosis had lower NPY and greater IL-1 beta concentrations in the serums compared with healthy control subjects. NPY expression was mainly observed around bronchial epithelial cells in human idiopathic pulmonary fibrosis lungs. These data suggest that NPY plays a protective role against pulmonary fibrosis by suppressing IL-1 beta release, and manipulating the NPY-Y1 receptor axis could be a potential therapeutic strategy for delaying disease progression. en-copyright= kn-copyright= en-aut-name=ItanoJunko en-aut-sei=Itano en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TaniguchiAkihiko en-aut-sei=Taniguchi en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SenooSatoru en-aut-sei=Senoo en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=GionYuka en-aut-sei=Gion en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EgusaYuria en-aut-sei=Egusa en-aut-mei=Yuria kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GuoLili en-aut-sei=Guo en-aut-mei=Lili kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OdaNaohiro en-aut-sei=Oda en-aut-mei=Naohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ArakiKota en-aut-sei=Araki en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MiyaharaNobuaki en-aut-sei=Miyahara en-aut-mei=Nobuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=6 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=7 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=8 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences kn-affil= affil-num=11 en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital kn-affil= en-keyword=idiopathic pulmonary fibrosis kn-keyword=idiopathic pulmonary fibrosis en-keyword=NPY kn-keyword=NPY en-keyword=IL-1 beta; bleomycin kn-keyword=IL-1 beta; bleomycin en-keyword=bronchial epithelial cells kn-keyword=bronchial epithelial cells END start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=1 article-no= start-page=35 end-page=40 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=2022 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Transformed diffuse large B-cell lymphoma from marginal zone lymphoma in the anterior mediastinum: A case report and review of the literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=Marginal zone lymphoma (MZL) arising from the anterior mediastinum is rare. In the majority of reported cases, the tumor was incidentally discovered, reflecting its indolent clinical features. We present a 38-year-old woman who had no medical history, and presented with a bulky anterior mediastinal tumor complicated by life-threatening compression of the vasculature and bronchi. Biopsy specimens of the neoplasm suggested transformed diffuse large B-cell lymphoma (DLBCL) from MZL. To our best knowledge, this is the first case report of anterior mediastinum MZL associated with an aggressive clinical course and life-threatening complications likely due to transformation to DLBCL. en-copyright= kn-copyright= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TabataTetsuya en-aut-sei=Tabata en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShibataRei en-aut-sei=Shibata en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiTatsuya en-aut-sei=Nishi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KatoYuka en-aut-sei=Kato en-aut-mei=Yuka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakasukaHiroki en-aut-sei=Takasuka en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KiuraKatsuyuki en-aut-sei=Kiura en-aut-mei=Katsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Respiratory and Allergy, Okayama University Hospital kn-affil= affil-num=6 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Transfusion Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Respiratory and Allergy, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=marginal zone lymphoma kn-keyword=marginal zone lymphoma en-keyword=diffuse large B-cell lymphoma kn-keyword=diffuse large B-cell lymphoma en-keyword=anterior mediastinum kn-keyword=anterior mediastinum en-keyword=cystic lesions kn-keyword=cystic lesions END start-ver=1.4 cd-journal=joma no-vol=60 cd-vols= no-issue=19 article-no= start-page=3155 end-page=3160 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Nodal Peripheral T-cell Lymphoma with T Follicular Helper Phenotype Presenting as Chorea During Treatment: A Case Report and Literature Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 72-year-old man presented with chorea while undergoing treatment for recurrence of nodal peripheral T-cell lymphoma with T follicular helper (TFH) phenotype. An examination by brain N-isopropyl-p-iodoamphetamine (I-123-IMP)-single photon emission computed tomography (SPECT) revealed no abnormalities other than a decreased cerebral blood flow (CBF) in the left striatum. After four courses of salvage chemotherapy, his clinical symptoms and asymmetric cerebral perfusion improved, suggesting that the decreased CBF had caused chorea. The significance of brain SPECT has not been fully clarified in patients with chorea-associated malignant lymphoma, warranting further investigations. Brain SPECT is an alternative approach to identify abnormalities in such patients. en-copyright= kn-copyright= en-aut-name=KitamuraWataru en-aut-sei=Kitamura en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YukawaRyoya en-aut-sei=Yukawa en-aut-mei=Ryoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiRyo en-aut-sei=Sasaki en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaChikamasa en-aut-sei=Yoshida en-aut-mei=Chikamasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakasukaHiroki en-aut-sei=Takasuka en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiwaraHideaki en-aut-sei=Fujiwara en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology, Okayama City Hospital kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Division of Clinical Laboratory, Okayama University Hospital kn-affil= affil-num=11 en-affil=Division of Blood Transfusion, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Neurology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=peripheral T-cell lymphoma kn-keyword=peripheral T-cell lymphoma en-keyword=chorea kn-keyword=chorea en-keyword=single photon-emission computed tomography kn-keyword=single photon-emission computed tomography END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=1 article-no= start-page=13125 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210623 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reduced dose of PTCy followed by adjuvant alpha-galactosylceramide enhances GVL effect without sacrificing GVHD suppression en-subtitle= kn-subtitle= en-abstract= kn-abstract=Posttransplantation cyclophosphamide (PTCy) has become a popular option for haploidentical hematopoietic stem cell transplantation (HSCT). However, personalized methods to adjust immune intensity after PTCy for each patient's condition have not been well studied. Here, we investigated the effects of reducing the dose of PTCy followed by alpha -galactosylceramide (alpha -GC), a ligand of iNKT cells, on the reciprocal balance between graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect. In a murine haploidentical HSCT model, insufficient GVHD prevention after reduced-dose PTCy was efficiently compensated for by multiple administrations of alpha -GC. The ligand treatment maintained the enhanced GVL effect after reduced-dose PTCy. Phenotypic analyses revealed that donor-derived B cells presented the ligand and induced preferential skewing to the NKT2 phenotype rather than the NKT1 phenotype, which was followed by the early recovery of all T cell subsets, especially CD4(+)Foxp3(+) regulatory T cells. These studies indicate that alpha -GC administration soon after reduced-dose PTCy restores GVHD-preventing activity and maintains the GVL effect, which is enhanced by reducing the dose of PTCy. Our results provide important information for the development of a novel strategy to optimize PTCy-based transplantation, particularly in patients with a potential relapse risk. en-copyright= kn-copyright= en-aut-name=NakamuraMakoto en-aut-sei=Nakamura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MeguriYusuke en-aut-sei=Meguri en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IkegawaShuntaro en-aut-sei=Ikegawa en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SumiiYuichi en-aut-sei=Sumii en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FukumiTakuya en-aut-sei=Fukumi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwamotoMiki en-aut-sei=Iwamoto en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SandoYasuhisa en-aut-sei=Sando en-aut-mei=Yasuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugiuraHiroyuki en-aut-sei=Sugiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=Fukuda-KawaguchiEmi en-aut-sei=Fukuda-Kawaguchi en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshiiYasuyuki en-aut-sei=Ishii en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=REGiMMUNE Corporation kn-affil= affil-num=14 en-affil=REGiMMUNE Corporation kn-affil= affil-num=15 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=59 cd-vols= no-issue=21 article-no= start-page=2757 end-page=2761 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Adult T-cell Leukemia-lymphoma with Primary Breast Involvement: A Case Report and Literature Review en-subtitle= kn-subtitle= en-abstract= kn-abstract=Breast involvement of Adult T-cell leukemia-lymphoma (ATLL) is extremely rare, and the data on the characteristics are limited. We herein describe a 49-year-old woman who presented with skin involvement of ATLL. Positron emission tomography/computed tomography showed bilateral breast lesions. Although the patient once achieved a complete metabolic response, a relapse of her ATLL occurred. The patient received subsequent allogeneic hematopoietic stem cell transplantation (HSCT). To our knowledge, only four cases of ATLL with breast involvement have previously been reported, and the prognoses have generally been poor. Breast lesions of ATLL have aggressive features, and intensive systemic chemotherapy and HSCT are required to improve survival. en-copyright= kn-copyright= en-aut-name=KobayashiHiroki en-aut-sei=Kobayashi en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IgawaTakuro en-aut-sei=Igawa en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeMasaya en-aut-sei=Abe en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MeguriYusuke en-aut-sei=Meguri en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MatsuokaKen-ichi en-aut-sei=Matsuoka en-aut-mei=Ken-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Transfusion Medicine, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= en-keyword=adult T-cell leukemia-lymphoma kn-keyword=adult T-cell leukemia-lymphoma en-keyword=breast involvement kn-keyword=breast involvement en-keyword=positron emission tomography/computed tomography kn-keyword=positron emission tomography/computed tomography END start-ver=1.4 cd-journal=joma no-vol=10 cd-vols= no-issue=1 article-no= start-page=17237 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201014 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Photodynamic therapy (PDT) is an emerging treatment for various solid cancers. We recently reported that tumor cell lines and patient specimens from adult T cell leukemia/lymphoma (ATL) are susceptible to specific cell death by visible light exposure after a short-term culture with 5-aminolevulinic acid, indicating that extracorporeal photopheresis could eradicate hematological tumor cells circulating in peripheral blood. As a bridge from basic research to clinical trial of PDT for hematological malignancies, we here examined the efficacy of ALA-PDT on various lymphoid malignancies with circulating tumor cells in peripheral blood. We also examined the effects of ALA-PDT on tumor cells before and after conventional chemotherapy. With 16 primary blood samples from 13 patients, we demonstrated that PDT efficiently killed tumor cells without influencing normal lymphocytes in aggressive diseases such as acute ATL. Importantly, PDT could eradicate acute ATL cells remaining after standard chemotherapy or anti-CCR4 antibody, suggesting that PDT could work together with other conventional therapies in a complementary manner. The responses of PDT on indolent tumor cells were various but were clearly depending on accumulation of protoporphyrin IX, which indicates the possibility of biomarker-guided application of PDT. These findings provide important information for developing novel therapeutic strategy for hematological malignancies. en-copyright= kn-copyright= en-aut-name=SandoYasuhisa en-aut-sei=Sando en-aut-mei=Yasuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuokaKen-Ichi en-aut-sei=Matsuoka en-aut-mei=Ken-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SumiiYuichi en-aut-sei=Sumii en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KondoTakumi en-aut-sei=Kondo en-aut-mei=Takumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkegawaShuntaro en-aut-sei=Ikegawa en-aut-mei=Shuntaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiuraHiroyuki en-aut-sei=Sugiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakamuraMakoto en-aut-sei=Nakamura en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwamotoMiki en-aut-sei=Iwamoto en-aut-mei=Miki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MeguriYusuke en-aut-sei=Meguri en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujiiKeiko en-aut-sei=Fujii en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FujiiNobuharu en-aut-sei=Fujii en-aut-mei=Nobuharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=UtsunomiyaAtae en-aut-sei=Utsunomiya en-aut-mei=Atae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OkaTakashi en-aut-sei=Oka en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=15 en-affil=Department of Hematology, Imamura General Hospital kn-affil= affil-num=16 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=T-cell lymphoma kn-keyword=T-cell lymphoma en-keyword=Targeted therapies kn-keyword=Targeted therapies END start-ver=1.4 cd-journal=joma no-vol=2020 cd-vols= no-issue= article-no= start-page=7947540 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200409 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Intestinal Diffuse Large B-Cell Lymphoma in a Patient with Systemic Lupus Erythematosus en-subtitle= kn-subtitle= en-abstract= kn-abstract=A 44-year-old Japanese woman with systemic lupus erythematosus (SLE) presented to our hospital with abdominal pain. Radiological and endoscopic examinations led to the diagnosis of diffuse large B-cell lymphoma of the jejunum, which was subsequently resected. Patients with SLE reportedly have an increased risk of non-Hodgkin lymphoma, as demonstrated by our patient. Hence, lymphoma should be considered in the differential diagnosis of neoplastic lesions emerging in SLE patients. In addition, flow cytometry using endoscopically biopsied fragments is useful for the immediate diagnosis of lymphoma, leading to timely and accurate preoperative staging. en-copyright= kn-copyright= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakahashiTakahide en-aut-sei=Takahashi en-aut-mei=Takahide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtaYoko en-aut-sei=Ota en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AsadaNoboru en-aut-sei=Asada en-aut-mei=Noboru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YanoShuya en-aut-sei=Yano en-aut-mei=Shuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UkaMayu en-aut-sei=Uka en-aut-mei=Mayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraRei en-aut-sei=Nakamura en-aut-mei=Rei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=BabaYuki en-aut-sei=Baba en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Division of Medical Support, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pathology & Experimental Medicine, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Radiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences kn-affil= END