Allogeneic hematopoietic stem cell transplantation could overcome the poor prognosis of DNMT3AmutNPM1mutFLT3-ITDmut in acute myeloid leukemia: real-world multicenter analysis in China.

Wenxuan HUO; Yifan SHEN; Jiayu HUANG; Yang YANG; Shuang FAN; Xiaosu ZHAO; Qi WEN; Luxiang WANG; Chuanhe JIANG; Yang CAO; Xiaodong MO; Yang XU; Xiaoxia HU

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Allogeneic hematopoietic stem cell transplantation could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in acute myeloid leukemia: real-world multicenter analysis in China.

Author: Wenxuan HUO ¹ ; Yifan SHEN ² ; Jiayu HUANG ³ ; Yang YANG ⁴ ; Shuang FAN ¹ ; Xiaosu ZHAO ¹ ; Qi WEN ¹ ; Luxiang WANG ³ ; Chuanhe JIANG ³ ; Yang CAO ⁵ ; Xiaodong MO ⁶ ; Yang XU ⁷ ; Xiaoxia HU ^{8
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Author Information

1. Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
2. National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China.
3. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
4. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
5. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. yangcao@tjh.tjmu.edu.cn.
6. Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China. moxiaodong@pkuph.edu.cn.
7. National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China. yangxu@suda.edu.cn.
8. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. hu_xiaoxia@
9. com.
Publication Type:Multicenter Study
Keywords: DNMT3A mutation; FLT3-ITD mutation; NPM1 mutation; acute myeloid leukemia; allogeneic hematopoietic stem cell transplantation; triple mutation
MeSH: Humans; Nucleophosmin; Leukemia, Myeloid, Acute/mortality*; Hematopoietic Stem Cell Transplantation/methods*; Male; Female; DNA Methyltransferase 3A; Adult; China; Retrospective Studies; DNA (Cytosine-5-)-Methyltransferases/genetics*; Middle Aged; Prognosis; fms-Like Tyrosine Kinase 3/genetics*; Mutation; Young Adult; Transplantation, Homologous; Nuclear Proteins/genetics*; Adolescent; Aged
From: Frontiers of Medicine 2025;19(1):90-100
CountryChina
Language:English
Abstract: The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.