title: Allogeneic hematopoietic stem cell transplantation could improve survival of cytogenetically normal adult acute myeloid leukemia patients with DNMT3A mutations.
abstract: DNMT3A mutations are frequent in cytogenetically normal acute myeloid leukemia (cn-AML) patients and associated with poor survival. The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in DNMT3A(mut) cn-AML patients remains unclear. In this study, we retrospectively analyzed the prognostic impact of DNMT3A mutations and explored the role of allo-HSCT in 308 cn-AML patients who received consolidation of intensive chemotherapy or allo-HSCT in our center from March 2005 to May 2014. In the whole cohort, 63 patients (20.5%) were identified with DNMT3A exon 23 mutations and R882H was the most frequent variant. DNMT3A(mut) patients had shorter overall survival (3-year OS: 31.9% vs. 52.0%, P = 0.009) and disease-free survival (3-year DFS: 21.8% vs. 40.1%, P = 0.004) compared with DNMT3A(wt) patients. Based on FLT3/NPM1/CEBPA mutations, 308 cn-AML patients were divided into favorable/intermediate group (n = 262) and unfavorable group (n = 46). There were no significant differences in 3-year OS and 3-year DFS between DNMT3A(mut) and DNMT3A(wt) patients in both favorable/intermediate and unfavorable groups. Additionally, in multivariate analysis, DNMT3A mutation remained an independent adverse prognostic factor for the survival. In the DNMT3A(mut) cohort, 23 complete remission (CR) patients received allo-HSCT consolidation and 32 CR patients received chemotherapy consolidation, dramatic differences were observed in 3-year OS (51.7% vs. 28.9%, P = 0.048) and 3-year DFS (41.6% vs. 14.9%, P = 0.024) between allo-HSCT group and chemotherapy group. Collectively, DNMT3A mutation is a poor prognostic factor for cn-AML patients and allo-HSCT could improve survival of cn-AML patients with DNMT3A mutations.
authors.affiliation: Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.|Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China.|Suzhou Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Lin
authors.initials: L
authors.lastname: Ding
authors.affiliation: Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.|Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.|Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China.|Suzhou Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, People's Republic of China.
authors.forename: Aining
authors.initials: A
authors.lastname: Sun
authors.affiliation: Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.|Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China.
authors.forename: Suning
authors.initials: S
authors.lastname: Chen
authors.affiliation: Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.|Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China.|Suzhou Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, People's Republic of China.
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D020732:Cytogenetic Analysis; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D005260:Female; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D014184:Transplantation, Homologous; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C000717967:DNMT3A protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3