Allogeneic hematopoietic stem cell transplantation could improve survival of cytogenetically normal adult acute myeloid leukemia patients with DNMT3A mutations. Issue 11 (November 2015)

• Record Type: Journal Article
• Authors: Xu, Yang; Sun, Yanjun; Shen, Hongjie; Ding, Lin; Yang, Zhen; Qiu, Huiying; Sun, Aining; Chen, Suning; Wu, Depei
• Is Part Of: American journal of hematology. Volume 90:Issue 11(2015:Nov.)
• Page Start: 992
• Page End: 997
• Publication Date: 2015-11
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.24135
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>DNMT3A</italic> 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 <italic>DNMT3A</italic><sup>mut</sup> cn‐AML patients remains unclear. In this study, we retrospectively analyzed the prognostic impact of <italic>DNMT3A</italic> 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 <italic>DNMT3A</italic> exon 23 mutations and R882H was the most frequent variant. <italic>DNMT3A</italic><sup>mut</sup> patients had shorter overall survival (3‐year OS: 31.9% vs. 52.0%, <italic>P</italic> = 0.009) and disease‐free survival (3‐year DFS: 21.8% vs. 40.1%, <italic>P</italic> = 0.004) compared with <italic>DNMT3A</italic><sup>wt</sup> patients. Based on <italic>FLT3/NPM1/CEBPA</italic> mutations, 308 cn‐AML patients were divided into favorable/intermediate group (<italic>n</italic> = 262) and unfavorable group (<italic>n</italic> = 46). There were no significant differences in 3‐year OS and 3‐year DFS between <italic>DNMT3A</italic><sup>mut</sup> and <italic>DNMT3A</italic><sup>wt</sup> patients in both favorable/intermediate and unfavorable groups. Additionally, in multivariate analysis, <italic>DNMT3A</italic> mutation remained an independent adverse prognostic factor for the survival. In the <italic>DNMT3A</italic><sup>mut</sup> 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%, <italic>P</italic> = 0.048) and 3‐year DFS (41.6% vs. 14.9%, <italic>P</italic> = 0.024) between allo‐HSCT group and chemotherapy group. Collectively, <italic>DNMT3A</italic> mutation is a poor prognostic factor for cn‐AML patients and allo‐HSCT could improve survival of cn‐AML patients with <italic>DNMT3A</italic> mutations. Am. J. Hematol. 90:992–997, 2015. © 2015 Wiley Periodicals, Inc.</p> </abstract>