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Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma

Kameda, Takuro Kataoka, Keisuke Kamiunten, Ayako Hidaka, Michihiro Miyoshi, Hiroaki Nakano, Nobuaki Nosaka, Kisato Yoshimitsu, Makoto Yasunaga, Jun-Ichirou Kogure, Yasunori Shide, Kotaro Miyahara, Masaharu Sakamoto, Takashi Akizuki, Keiichi Hidaka, Tomonori Kubuki, Yoko Koya, Junji Kawano, Noriaki Yamashita, Kiyoshi Kawano, Hiroshi Toyama, Takanori Maeda, Kouichi Marutsuka, Kosuke Imaizumi, Yoshitaka Kato, Koji Sugio, Takeshi Tokunaga, Masahito Tashiro, Yukie Takaori-Kondo, Akifumi Miyazaki, Yasushi Akashi, Koichi Ishitsuka, Kenji Matsuoka, Masao Ohshima, Koichi Watanabe, Toshiki Kitanaka, Akira Utsunomiya, Atae Ogawa, Seishi Shimoda, Kazuya 京都大学 DOI:10.3324/haematol.2022.281510

2023.08

概要

The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment. 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 high-risk 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 ATL-PI, 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).

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Haematologica | 108 August 2023

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