{"title":"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","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":"<p><strong>Objective: </strong>Acute myeloid leukemia (AML) patients with internal tandem duplications in the FMS-like tyrosine kinase 3 receptor gene (<i>FLT3</i>-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.</p><p><strong>Methods: </strong>We consecutively enrolled <i>FLT3</i>-ITD AML patients undergoing transplantation at three centers. By integrating genetic profiles with clinical information, we assessed their impact on transplant outcomes.</p><p><strong>Results: </strong>A total of 196 patient were eligible in the analysis, among whom 14% harbored myelodysplasia-related (MR) mutations, including <i>ASXL1</i>, <i>BCOR</i>, <i>EZH2</i>, <i>RUNX1</i>, <i>SF3B1</i>, <i>SRSF2</i>, <i>STAG2</i>, <i>U2AF1</i>, and <i>ZRSR2</i>. 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]. <i>DNMT3A</i> 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).</p><p><strong>Conclusions: </strong>Patients with myelodysplasia-related gene mutations (<i>MRmut</i>) and/or <i>DNMT3A</i> mutations experienced inferior outcomes after transplantation, requiring further exploration. Furthermore, similar prognoses among CR patients highlighted the need for monitoring specific molecular residual lesions.</p>","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":"{\"title\":\"Impact of clinical characteristics and genetic profiles on outcomes of allogeneic stem cell transplantation with sorafenib maintenance in <i>FLT3</i>-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\":\"<p><strong>Objective: </strong>Acute myeloid leukemia (AML) patients with internal tandem duplications in the FMS-like tyrosine kinase 3 receptor gene (<i>FLT3</i>-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.</p><p><strong>Methods: </strong>We consecutively enrolled <i>FLT3</i>-ITD AML patients undergoing transplantation at three centers. By integrating genetic profiles with clinical information, we assessed their impact on transplant outcomes.</p><p><strong>Results: </strong>A total of 196 patient were eligible in the analysis, among whom 14% harbored myelodysplasia-related (MR) mutations, including <i>ASXL1</i>, <i>BCOR</i>, <i>EZH2</i>, <i>RUNX1</i>, <i>SF3B1</i>, <i>SRSF2</i>, <i>STAG2</i>, <i>U2AF1</i>, and <i>ZRSR2</i>. 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]. <i>DNMT3A</i> 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).</p><p><strong>Conclusions: </strong>Patients with myelodysplasia-related gene mutations (<i>MRmut</i>) and/or <i>DNMT3A</i> mutations experienced inferior outcomes after transplantation, requiring further exploration. Furthermore, similar prognoses among CR patients highlighted the need for monitoring specific molecular residual lesions.</p>\",\"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}","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}
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.
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.
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.
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