Haematologica (Feb 2023)
Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma
- Takuro Kameda,
- Keisuke Kataoka,
- Ayako Kamiunten,
- Michihiro Hidaka,
- Hiroaki Miyoshi,
- Nobuaki Nakano,
- Kisato Nosaka,
- Makoto Yoshimitsu,
- Jun-ichirou Yasunaga,
- Yasunori Kogure,
- Kotaro Shide,
- Masaharu Miyahara,
- Takashi Sakamoto,
- Keiichi Akizuki,
- Tomonori Hidaka,
- Yoko Kubuki,
- Junji Koya,
- Noriaki Kawano,
- Kiyoshi Yamashita,
- Hiroshi Kawano,
- Takanori Toyama,
- Kouichi Maeda,
- Kosuke Marutsuka,
- Yoshitaka Imaizumi,
- Koji Kato,
- Takeshi Sugio,
- Masahito Tokunaga,
- Yukie Tashiro,
- Akifumi Takaori-Kondo,
- Yasushi Miyazaki,
- Koichi Akashi,
- Kenji Ishitsuka,
- Masao Matsuoka,
- Koichi Ohshima,
- Toshiki Watanabe,
- Akira Kitanaka,
- Atae Utsunomiya,
- Seishi Ogawa,
- Kazuya Shimoda
Affiliations
- Takuro Kameda
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki
- Keisuke Kataoka
- Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo
- Ayako Kamiunten
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki
- Michihiro Hidaka
- National Hospital Organization Kumamoto Medical Center, Kumamoto
- Hiroaki Miyoshi
- Department of Pathology, Kurume University School of Medicine, Kurume
- Nobuaki Nakano
- Department of Hematology, Imamura General Hospital, Kagoshima
- Kisato Nosaka
- Department of Hematology, Rheumatology and Infectious Diseases, Faculty of Life Sciences, Kumamoto University of Medicine, Kumamoto
- Makoto Yoshimitsu
- Department of Hematology and Rheumatology, Kagoshima University Hospital, Kagoshima
- Jun-ichirou Yasunaga
- Department of Hematology, Rheumatology and Infectious Diseases, Faculty of Life Sciences, Kumamoto University of Medicine, Kumamoto, Japan; Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto
- Yasunori Kogure
- Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo
- Kotaro Shide
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki
- Masaharu Miyahara
- Department of Internal Medicine, Karatsu Red Cross Hospital, Saga
- Takashi Sakamoto
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto
- Keiichi Akizuki
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki
- Tomonori Hidaka
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki
- Yoko Kubuki
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki
- Junji Koya
- Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo
- Noriaki Kawano
- Department of Internal medicine, Miyazaki Prefectural Miyazaki Hospital, Miyazaki
- Kiyoshi Yamashita
- Department of Internal medicine, Miyazaki Prefectural Miyazaki Hospital, Miyazaki
- Hiroshi Kawano
- Department of Internal medicine, Koga General Hospital, Miyazaki
- Takanori Toyama
- Department of Internal medicine, Miyazaki Prefectural Nobeoka Hospital, Miyazaki
- Kouichi Maeda
- National Hospital Organization Miyakonojo Medical center, Miyazaki
- Kosuke Marutsuka
- Department of Anatomic Pathology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki
- Yoshitaka Imaizumi
- Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki
- Koji Kato
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka
- Takeshi Sugio
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka
- Masahito Tokunaga
- Department of Hematology, Imamura General Hospital, Kagoshima
- Yukie Tashiro
- Department of Pathology, Imamura General Hospital, Kagoshima
- Akifumi Takaori-Kondo
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto
- Yasushi Miyazaki
- Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki
- Koichi Akashi
- Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka
- Kenji Ishitsuka
- Department of Hematology and Rheumatology, Kagoshima University Hospital, Kagoshima
- Masao Matsuoka
- Department of Hematology, Rheumatology and Infectious Diseases, Faculty of Life Sciences, Kumamoto University of Medicine, Kumamoto
- Koichi Ohshima
- Department of Pathology, Kurume University School of Medicine, Kurume
- Toshiki Watanabe
- Department of Practical Management of Medical Information, St Marianna University, Graduate School of Medicine, Tokyo
- Akira Kitanaka
- Department of Laboratory Medicine, Kawasaki Medical School, Kurashiki
- Atae Utsunomiya
- Department of Hematology, Imamura General Hospital, Kagoshima
- Seishi Ogawa
- Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto
- Kazuya Shimoda
- Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki
- DOI
- https://doi.org/10.3324/haematol.2022.281510
- Journal volume & issue
-
Vol. 108,
no. 8
Abstract
The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment. In order to identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and highrisk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] =5.46; P<0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR=2.33; P=0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATLPI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3).
