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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 

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 (AML(FLT3-ITD+/NPM1+)) depends on the allelic ratio of FLT3-ITD. But despite a low or high allelic ratio of FLT3...

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Autores principales: Huang, Yan, Hu, Juan, Lu, Ting, Luo, Yi, Shi, Jimin, Wu, Wenjun, Han, Xiaoyan, Zheng, Weiyan, He, Jingsong, Cai, Zhen, Wei, Guoqing, Huang, He, Sun, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512860/
https://www.ncbi.nlm.nih.gov/pubmed/31190985
http://dx.doi.org/10.2147/CMAR.S194523
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author Huang, Yan
Hu, Juan
Lu, Ting
Luo, Yi
Shi, Jimin
Wu, Wenjun
Han, Xiaoyan
Zheng, Weiyan
He, Jingsong
Cai, Zhen
Wei, Guoqing
Huang, He
Sun, Jie
author_facet Huang, Yan
Hu, Juan
Lu, Ting
Luo, Yi
Shi, Jimin
Wu, Wenjun
Han, Xiaoyan
Zheng, Weiyan
He, Jingsong
Cai, Zhen
Wei, Guoqing
Huang, He
Sun, Jie
author_sort Huang, Yan
collection PubMed
description 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 (AML(FLT3-ITD+/NPM1+)) depends on the allelic ratio of FLT3-ITD. But despite a low or high allelic ratio of FLT3-ITD, AML(FLT3-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 AML(FLT3-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 AML(FLT3-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 AML(FLT3-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, AML(FLT3-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. AML(FLT3-ITD+/NPM1+) patients with DNMT3A R882 mutation had a very poor prognosis, and allo-HSCT could moderately improve their survival.
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spelling pubmed-65128602019-06-12 Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis  Huang, Yan Hu, Juan Lu, Ting Luo, Yi Shi, Jimin Wu, Wenjun Han, Xiaoyan Zheng, Weiyan He, Jingsong Cai, Zhen Wei, Guoqing Huang, He Sun, Jie Cancer Manag Res Original Research 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 (AML(FLT3-ITD+/NPM1+)) depends on the allelic ratio of FLT3-ITD. But despite a low or high allelic ratio of FLT3-ITD, AML(FLT3-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 AML(FLT3-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 AML(FLT3-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 AML(FLT3-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, AML(FLT3-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. AML(FLT3-ITD+/NPM1+) patients with DNMT3A R882 mutation had a very poor prognosis, and allo-HSCT could moderately improve their survival. Dove 2019-05-08 /pmc/articles/PMC6512860/ /pubmed/31190985 http://dx.doi.org/10.2147/CMAR.S194523 Text en © 2019 Huang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Huang, Yan
Hu, Juan
Lu, Ting
Luo, Yi
Shi, Jimin
Wu, Wenjun
Han, Xiaoyan
Zheng, Weiyan
He, Jingsong
Cai, Zhen
Wei, Guoqing
Huang, He
Sun, Jie
Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis 
title Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis 
title_full Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis 
title_fullStr Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis 
title_full_unstemmed Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis 
title_short Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis 
title_sort acute myeloid leukemia patient with flt3-itd and npm1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in cr1 for better prognosis 
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512860/
https://www.ncbi.nlm.nih.gov/pubmed/31190985
http://dx.doi.org/10.2147/CMAR.S194523
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