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

Author:

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

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).

Publisher

Ferrata Storti Foundation (Haematologica)

Subject

Hematology

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