American Society of Hematology
Acta Medica Okayama
2473-9529
7
24
2023
Distribution and clinical impact of molecular subtypes with dark zone signature of DLBCL in a Japanese real-world study
7459
7470
EN
Tomohiro
Urata
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yusuke
Naoi
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Aixiang
Jiang
British Columbia Cancer, Centre for Lymphoid Cancer
Merrill
Boyle
British Columbia Cancer, Centre for Lymphoid Cancer
Kazutaka
Sunami
Department of Hematology, NHO Okayama Medical Center
Toshi
Imai
Department of Hematology and Blood Transfusion, Kochi Health Sciences Center
Yuichiro
Nawa
Division of Hematology, Ehime Prefectural Central Hospital
Yasushi
Hiramatsu
Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital
Kazuhiko
Yamamoto
Department of Hematology and Oncology, Okayama City Hospital
Soichiro
Fujii
Department of Hematology, Japanese Red Cross Okayama Hospital
Isao
Yoshida
Department of Hematologic Oncology, NHO Shikoku Cancer Center
Tomofumi
Yano
Department of Internal Medicine, Okayama Rosai Hospital
Ryota
Chijimatsu
Center for Comprehensive Genomic Medicine, Okayama University Hospital
Hiroyuki
Murakami
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kazuhiro
Ikeuchi
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hiroki
Kobayashi
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Katsuma
Tani
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hideki
Ujiie
Center for Comprehensive Genomic Medicine, Okayama University Hospital
Hirofumi
Inoue
Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
Shuta
Tomida
Center for Comprehensive Genomic Medicine, Okayama University Hospital
Akira
Yamamoto
Department of Hematology and Oncology, Okayama University Hospital
Takumi
Kondo
Department of Hematology and Oncology, Okayama University Hospital
Hideaki
Fujiwara
Department of Hematology and Oncology, Okayama University Hospital
Noboru
Asada
Department of Hematology and Oncology, Okayama University Hospital
Hisakazu
Nishimori
Department of Hematology and Oncology, Okayama University Hospital
Keiko
Fujii
Department of Hematology and Oncology, Okayama University Hospital
Nobuharu
Fujii
Department of Hematology and Oncology, Okayama University Hospital
Ken-ichi
Matsuoka
Department of Hematology and Oncology, Okayama University Hospital
Keisuke
Sawada
Department of Pathology, Saitama Medical Center, Saitama Medical University
Shuji
Momose
Department of Pathology, Saitama Medical Center, Saitama Medical University
Jun-ichi
Tamaru
Department of Pathology, Saitama Medical Center, Saitama Medical University
Asami
Nishikori
Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
Yasuharu
Sato
Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences
Tadashi
Yoshino
Department of Pathology, Okayama University
Yoshinobu
Maeda
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
David W.
Scott
British Columbia Cancer, Centre for Lymphoid Cancer
Daisuke
Ennishi
Department of Hematology and Oncology, Okayama University Hospital
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.
No potential conflict of interest relevant to this article was reported.
American Society of Hematology
Acta Medica Okayama
2473-9529
2
15
2018
Outcomes of patients who developed subsequent solid cancer after hematopoietic cell transplantation
1901
1903
EN
Yoshihiro
Inamoto
National Cancer Center Hospital
Tomohiro
Matsuda
National Cancer Center Hospital
Ken
Tabuchi
Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
Saiko
Kurosawa
National Cancer Center Hospital
Hideki
Nakasone
Saitama Medical Center, Jichi Medical University
Hisakazu
Nishimori
Okayama University Hospital
Satoshi
Yamasaki
National Hospital Organization Kyushu Medical Center
Noriko
Doki
Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
Koji
Iwato
Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital
Takehiko
Mori
Keio University School of Medicine
Satoshi
Takahashi
The Institute of Medical Science, The University of Tokyo
Hiromasa
Yabe
Tokai University Hospital,
Akio
Kohno
JA Aichi Konan Kosei Hospital
Hirohisa
Nakamae
Osaka City University
Toru
Sakura
Saiseikai Maebashi Hospital
Hisako
Hashimoto
Kobe City Medical Center General Hospital
Junichi
Sugita
Hokkaido University Hospital
Hiroatsu
Ago
Shimane Prefectural Central Hospital
Takahiro
Fukuda
National Cancer Center Hospital
Tatsuo
Ichinohe
Research Institute for Radiation Biology and Medicine, Hiroshima University
Yoshiko
Atsuta
Japanese Data Center for Hematopoietic Cell Transplantation
Takuya
Yamashita
St. Luke's International Hospital
Japan Society for Hematopoietic Cell Transplantation Late Effects and Quality of Life Working Group
To characterize the outcomes of patients who developed a particular subsequent solid cancer after hematopoietic cell transplantation (HCT), age at cancer diagnosis, survival, and causes of death were compared with the respective primary cancer in the general population, using data from the national HCT registry and population-based cancer registries in Japan. Among 31 867 patients who underwent a first HCT between 1990 and 2013 and had progression-free survival at 1 year, 713 patients developed subsequent solid cancer. The median age at subsequent solid cancer diagnosis was 55 years, which was significantly younger than the 67 years for primary cancer patients in the general population (P < .001). The overall survival probability was 60% at 3 years after diagnosis of subsequent solid cancer and differed according to cancer type. Development of most solid cancers was associated with an increased risk of subsequent mortality after HCT. Subsequent solid cancers accounted for 76% of causes of death. Overall survival probabilities adjusted for age, sex, and year of diagnosis were lower in the HCT population than in the general population for colon, bone/soft tissue, and central nervous system cancers and did not differ statistically for other cancers. In conclusion, most subsequent solid cancers occurred at younger ages than primary cancers, emphasizing the need for cancer screening at younger ages. Subsequent solid cancers showed similar or worse survival compared with primary cancers. Biological and genetic differences between primary and subsequent solid cancers remain to be determined.
No potential conflict of interest relevant to this article was reported.