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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
Haematologica (Roma), 08/2023, Volume: 108, Issue: 8Journal Article
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).
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