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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2019
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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. |
format | Online Article Text |
id | pubmed-6512860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
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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