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Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis 

Authors Huang Y, Hu J, Lu T, Luo Y, Shi J, Wu W, Han X, Zheng W, He J, Cai Z, Wei G, Huang H, Sun J

Received 25 November 2018

Accepted for publication 22 March 2019

Published 8 May 2019 Volume 2019:11 Pages 4129—4142

DOI https://doi.org/10.2147/CMAR.S194523

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 4

Editor who approved publication: Dr Beicheng Sun


Yan Huang,1–4* Juan Hu,1–4* Ting Lu,1–4 Yi Luo,1–4 Jimin Shi,1–4 Wenjun Wu,1–4 Xiaoyan Han,1–4 Weiyan Zheng,1–4 Jingsong He,1–4 Zhen Cai,1–4 Guoqing Wei,1–4 He Huang,1–4 Jie Sun1–4

1Bone Marrow Transplantation Center,the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China; 2Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China; 3Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China; 4Stem Cell Institute, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China

*These authors contributed equally to this work

Background: According to the recent National Comprehensive Cancer Network (NCCN) guidelines, the risk level in acute myeloid leukemia (AML) patients with FLT3-ITD and NPM1 double mutation (AMLFLT3-ITD+/NPM1+,) depends on the allelic ratio of FLT3-ITD. But despite a low or high allelic ratio of FLT3-ITD, AMLFLT3-ITD+/NPM1+, patients belong to the favorable or intermediate risk, for whom allogeneic stem cell transplantation is not obligated. However, some latest studies pointing out that NPM1 and FLT3-ITD double mutation patients showed an inferior prognosis, which have raised concern about the risk categorization and more effective treatment of AMLFLT3-ITD+/NPM1+, patients.
Methods: A total of 76 patients were selected for coexisting FLT3 and NPM1 mutations with normal cytogenetics. The prognostic risk factors were analyzed, and treatment strategies including allogeneic stem cell transplantati1on and chemotherapy were compared.
Results: In 76 AMLFLT3-ITD+/NPM1+, patients, 36.8% of patients had hyperleukocytosis (HL) and DNMT3A R882 mutation was the most common concomitant gene (23.7%). For 53 patients in the complete remission (CR), 22 had received allogeneic hematopoietic stem cell transplantation (allo-HSCT) on first complete remission (CR1). Patients in transplantation group had better overall survival (OS) and disease-free survival (DFS) than chemotherapy only (P=0.002 and 0.001, respectively). In multivariable Cox model analyses, HL and DNMT3A R882 mutation were independent adverse prognostic factors (all P<0.05) for AMLFLT3-ITD+/NPM1+, patients. Nevertheless, allo-HSCT was an independent good factor of OS and DFS (P=0.001 and 0.000; HR =0.173 and 0.138; 95% CI were 0.062–0.483 and 0.049–0.389). And allo-HSCT could moderately improve the poor prognosis of AML FLT3-ITD+/NPM1+/DNMT3A R882+,.
Conclusion: Although, AMLFLT3-ITD+/NPM1+, patients are categorized as favorable or intermediate risk levels according to recent NCCN and ELN guidelines, these patients should receive allo-HSCT in CR1 for a longer survival. AMLFLT3-ITD+/NPM1+, patients with DNMT3A R882 mutation had a very poor prognosis, and allo-HSCT could moderately improve their survival.

Keywords: FLT3-ITD, NPM1, DNMT3A R882, allo-HSCT

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