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
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).