ISSN: 1300-7777 E-ISSN: 1308-5263
FLT3-ITD compared with DNMT3A R882 mutation is a more powerful independent inferior prognostic factor in adult AML patients after Allogeneic Hematopoietic Stem Cell Transplantation: A retrospective cohort study [Turk J Hematol]
Turk J Hematol. Ahead of Print: TJH-40222 | DOI: 10.4274/tjh.2018.0017  

FLT3-ITD compared with DNMT3A R882 mutation is a more powerful independent inferior prognostic factor in adult AML patients after Allogeneic Hematopoietic Stem Cell Transplantation: A retrospective cohort study

Majid Teremmahi Ardestani1, Ahmad Kazemi1, Bahram Chahardouli2, Saeed Mohammadi2, Mohsen Nikbakht2, Shahrbano Rostami2, Mahdi Jalili2, Mohammad Vaezi2, Kamran Alimoghaddam2, Ardeshir Ghavamzadeh2
1Department of hematology, School of allied medical sciences, Iran university of medical sciences, Tehran, Iran
2Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran

Objective: To identify DNMT3A exon 23 mutations and their prognostic impact in the presence of FLT3-ITD and NPM1 mutations in acute myeloid leukemia (AML) patients treated with Allo-HSCT.
Materials and Methods: This study analyzed128 adult AML patients referred to the Hematology-Oncology & Stem Cell Research Center of Shariati hospital. FLT3-ITD and NPM1 mutations were detected using fragment analysis. For DNMT3A exon 23 mutation analysis, we used Sanger sequencing. Survival curves were estimated by the Kaplan-Meier method and the differences between groups were compared using Log-Rank test.
Results: The incidence of DNMT3A exon 23 mutations was 15.6% and the hotspot region R882 mutations were prominent. Overall survival (OS) and Relapse-free survival (RFS) were compared in patients with and without DNMT3A exon 23 mutations using univariate analysis and there was no significant difference between two groups of patients. On the contrary, the FLT3-ITD mutation significantly reduced the OS (p=0.009) and RFS (p=0.006) rates in AML patients after allogeneic hematopoietic cell transplantation (Allo-HSCT). In the next step, AML patients were divided into four groups according to DNMT3A and FLT3-ITD mutations. Patients with DNMT3A R882mut/FLT3-ITDpos had the worst OS and RFS. These results indicate that DNMT3A mutations alone cannot affect the clinical outcomes of AML patients treated with Allo-HSCT, but when accompanied by FLT3-ITD mutations, the overall survival was significantly reduced (5-year OS 0% for DNMT3AR882mut/FLT3-ITDpos patients vs 62% DNMT3AR882wt/FLT3-ITDneg, p=0.025) and relapse incidence rate increased.
Conclusion: It can be deduced that DNT3A R882mut/ FLT3-ITDpos is a poor prognostic factor in AML patients even after Allo-HSCT.

Keywords: DNMT3A R882, FLT3-ITD, Allo-HSCT, AML.




Corresponding Author: Shahrbano Rostami, Türkiye


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Impact Factor (2016) = 0.686