Post-azacitidine克隆大小预测骨髓增殖性疾病和相关骨髓系肿瘤患者的预后。
Post-azacitidine clone size predicts outcome of patients with myelodysplastic syndromes and related myeloid neoplasms.
发表日期：2023 Mar 29
作者：
Yasuhito Nannya, Magnus Tobiasson, Shinya Sato, Elsa Bernard, Shigeki Ohtake, June Takeda, Maria Creignou, Lanying Zhao, Manabu Kusakabe, Yuhei Shibata, Nobuhiko Nakamura, Mizuki Watanabe, Nobuhiro Hiramoto, Yusuke Shiozawa, Yuichi Shiraishi, Hiroko Tanaka, Kenichi Yoshida, Nobuyuki Kakiuchi, Hideki Makishima, Masahiro Marshall Nakagawa, Kensuke Usuki, Mitsumasa Watanabe, Kazunori Imada, Hiroshi Handa, Masataka Taguchi, Toru Kiguchi, Kazuma Ohyashiki, Takayuki Ishikawa, Akifumi Takaori-Kondo, Hisashi Tsurumi, Senji Kasahara, Shigeru Chiba, Tomoki Naoe, Satoru Miyano, Elli Papaemmanuil, Yasushi Miyazaki, Eva Hellström Lindberg, Seishi Ogawa
来源：
Bone & Joint Journal
摘要：
阿扎胞苷是治疗MDS相关疾病的主要治疗方法。我们研究的目的是阐明基因突变对血液学反应和总体生存率（OS）的影响，特别关注其治疗后克隆大小。我们招募了总计449名患有MDS或相关髓样肿瘤的患者。我们使用定向捕获测序分析了前期（n=449）和治疗后（n=289）骨髓样本中的基因突变，以评估基因突变及其治疗后克隆大小对治疗结果的影响。在Cox比例危险模型中，多击TP53突变（HR，2.03；95％CI，1.42-2.91；P<.001）、EZH2突变（HR，1.71；95％CI，1 .14-2.54；P = .009）和DDX41突变（HR，0.33；95％CI，0.17-0.62；P<.001）以及年龄、高危核型、低血小板和高原始细胞计数预测OS。治疗后的克隆大小考虑所有驱动器与国际工作组（IWG）反应显着相关（P<.001，趋势检验），除DDX41突变克隆外，它未能预测IWG反应。在结合IWG反应和治疗后克隆大小后，进一步提高了原始模型的预测效果，甚至比最近提出的分子预测模型IPSS-M更好（c指数，0.653比0.688；P <.001，似然比检验）。总之，评估治疗后克隆大小，以及治疗前突变概况和IWG反应，在阿扎胞苷治疗的骨髓增生异常综合症患者的更好预后方面发挥着作用。 版权所有©2023年美国血液学会。
Azacitidine is a mainstay of therapy for MDS-related diseases. The purpose of our study is to elucidate the effect of gene mutations on hematological response and overall survival (OS), particularly focusing on their post-treatment clone size. We enrolled a total of 449 patients with MDS or related myeloid neoplasms. They were analyzed for gene mutations in pre- (n=449) and post- (n=289) treatment bone marrow samples using targeted-capture sequencing to assess the impact of gene mutations and their post-treatment clone size on treatment outcomes. In Cox proportional hazard modeling, multi-hit TP53 mutation (HR, 2.03; 95% CI, 1.42-2.91; P<.001), EZH2 mutation (HR, 1.71; 95% CI, 1.14-2.54; P=.009), and DDX41 mutations (HR, 0.33; 95% CI, 0.17-0.62; P<.001), together with age, high-risk karyotypes, low platelet, and high blast counts, independently predicted OS. Post-treatment clone size accounting for all drivers significantly correlated with International Working Group (IWG)-response (P<.001, trend test), except for that of DDX41-mutated clones, which did not predict IWG-response. Combined, IWG-response and post-treatment clone size further improved the prediction of the original model and even that of a recently proposed molecular prediction model, IPSS-M (c-index, 0.653 vs 0.688; P<.001, likelihood ratio test). In conclusion, evaluation of post-treatment clone size, together with pre-treatment mutational profile as well as IWG-response have a role in better prognostication of azacitidine-treated myelodysplasia patients.Copyright © 2023 American Society of Hematology.