Impact of clinical characteristics and genetic profiles on outcomes of allogeneic stem cell transplantation with sorafenib maintenance in FLT3-ITD acute myeloid leukemia patients: A multi-center, retrospective study.

IF 6.3 2区医学 Q1 ONCOLOGY

Chinese Journal of Cancer Research Pub Date : 2025-08-30 DOI:10.21147/j.issn.1000-9604.2025.04.04

Yeqian Zhao, Chuanhe Jiang, Yi Luo, Guifang Ouyang, Lieguang Chen, Jian Yu, Yamin Tan, Xiaoyu Lai, Lizhen Liu, Huarui Fu, Yishan Ye, Luxin Yang, Congxiao Zhang, Jimin Shi, He Huang, Xiaoxia Hu, Yanmin Zhao

{"title":"Impact of clinical characteristics and genetic profiles on outcomes of allogeneic stem cell transplantation with sorafenib maintenance in FLT3-ITD acute myeloid leukemia patients: A multi-center, retrospective study.","authors":"Yeqian Zhao, Chuanhe Jiang, Yi Luo, Guifang Ouyang, Lieguang Chen, Jian Yu, Yamin Tan, Xiaoyu Lai, Lizhen Liu, Huarui Fu, Yishan Ye, Luxin Yang, Congxiao Zhang, Jimin Shi, He Huang, Xiaoxia Hu, Yanmin Zhao","doi":"10.21147/j.issn.1000-9604.2025.04.04","DOIUrl":null,"url":null,"abstract":"Objective: Acute myeloid leukemia (AML) patients with internal tandem duplications in the FMS-like tyrosine kinase 3 receptor gene (FLT3-ITD) receiving tyrosine kinase inhibitors maintenance after allogeneic hematopoietic stem cell transplantation (allo-HSCT) demonstrated improved survival outcomes, however, some still experienced relapse during the maintenance. This study aimed to explore risk factors which might be indicators for poor survival after allo-HSCT in this population.Methods: We consecutively enrolled FLT3-ITD AML patients undergoing transplantation at three centers. By integrating genetic profiles with clinical information, we assessed their impact on transplant outcomes.Results: A total of 196 patient were eligible in the analysis, among whom 14% harbored myelodysplasia-related (MR) mutations, including ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and ZRSR2. Co-mutant MR was independently associated with poorer overall survival (OS) [hazard ratio (HR): 2.4, 95% confidence interval (95% CI): 1.1-5.3, P=0.030]. DNMT3A co-mutations strongly predicted adverse survival and relapse [OS: HR: 2.1, 95% CI: 1.0-4.3, P=0.045; relapse-free survival (RFS): HR: 2.2, 95% CI: 1.1-4.1, P=0.017; cumulative incidence of relapse (CIR): HR: 2.3, 95% CI: 1.1-4.8, P=0.030]. Compared to patients with negative measurable residual disease (MRD) complete remission (CR), no significant differences were observed in CR patients with positive MRD, while those without CR exhibited significantly inferior outcomes (P=0.003).Conclusions: Patients with myelodysplasia-related gene mutations (MRmut) and/or DNMT3A mutations experienced inferior outcomes after transplantation, requiring further exploration. Furthermore, similar prognoses among CR patients highlighted the need for monitoring specific molecular residual lesions.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"37 4","pages":"521-533"},"PeriodicalIF":6.3000,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444344/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21147/j.issn.1000-9604.2025.04.04","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: Acute myeloid leukemia (AML) patients with internal tandem duplications in the FMS-like tyrosine kinase 3 receptor gene (FLT3-ITD) receiving tyrosine kinase inhibitors maintenance after allogeneic hematopoietic stem cell transplantation (allo-HSCT) demonstrated improved survival outcomes, however, some still experienced relapse during the maintenance. This study aimed to explore risk factors which might be indicators for poor survival after allo-HSCT in this population.

Methods: We consecutively enrolled FLT3-ITD AML patients undergoing transplantation at three centers. By integrating genetic profiles with clinical information, we assessed their impact on transplant outcomes.

Results: A total of 196 patient were eligible in the analysis, among whom 14% harbored myelodysplasia-related (MR) mutations, including ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and ZRSR2. Co-mutant MR was independently associated with poorer overall survival (OS) [hazard ratio (HR): 2.4, 95% confidence interval (95% CI): 1.1-5.3, P=0.030]. DNMT3A co-mutations strongly predicted adverse survival and relapse [OS: HR: 2.1, 95% CI: 1.0-4.3, P=0.045; relapse-free survival (RFS): HR: 2.2, 95% CI: 1.1-4.1, P=0.017; cumulative incidence of relapse (CIR): HR: 2.3, 95% CI: 1.1-4.8, P=0.030]. Compared to patients with negative measurable residual disease (MRD) complete remission (CR), no significant differences were observed in CR patients with positive MRD, while those without CR exhibited significantly inferior outcomes (P=0.003).

Conclusions: Patients with myelodysplasia-related gene mutations (MRmut) and/or DNMT3A mutations experienced inferior outcomes after transplantation, requiring further exploration. Furthermore, similar prognoses among CR patients highlighted the need for monitoring specific molecular residual lesions.

查看原文本刊更多论文

FLT3-ITD急性髓系白血病患者的临床特征和遗传特征对异体干细胞移植维持索拉非尼治疗结果的影响：一项多中心回顾性研究

目的：同种异体造血干细胞移植（alloo - hsct）后接受酪氨酸激酶抑制剂维持的fms样酪氨酸激酶3受体基因（FLT3-ITD）内串联重复的急性髓系白血病（AML）患者的生存结果得到改善，但一些患者在维持期间仍出现复发。本研究旨在探讨可能是该人群同种异体造血干细胞移植后生存不良指标的危险因素。方法：我们连续招募了在三个中心接受移植的FLT3-ITD AML患者。通过整合基因图谱和临床信息，我们评估了它们对移植结果的影响。结果：共有196例患者符合分析条件，其中14%携带骨髓增生异常相关（MR）突变，包括ASXL1、bor、EZH2、RUNX1、SF3B1、SRSF2、STAG2、U2AF1和ZRSR2。共突变MR与较差的总生存期（OS）独立相关[风险比（HR）： 2.4, 95%可信区间（95% CI）： 1.1-5.3， P=0.030]。DNMT3A共突变强烈预测不良生存和复发[OS: HR: 2.1, 95% CI: 1.0-4.3， P=0.045；无复发生存期（RFS）： HR: 2.2, 95% CI: 1.1 ~ 4.1， P=0.017；累积复发率（CIR）： HR: 2.3, 95% CI: 1.1 ~ 4.8， P=0.030。与可测量残余病（MRD）完全缓解（CR）阴性的患者相比，MRD阳性的CR患者无显著差异，而无CR的CR患者预后明显较差（P=0.003）。结论：骨髓增生异常相关基因突变（MRmut）和/或DNMT3A突变患者移植后预后较差，需要进一步探索。此外，CR患者的预后相似，强调了监测特定分子残留病变的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Chinese Journal of Cancer Research 医学-肿瘤学

自引率

9.80%

发文量

1726

审稿时长

4.5 months

期刊介绍： Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.