Prognostic impact of low allelic ratio FLT3-ITD and NPM1 mutation in acute myeloid leukemia

In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation (NPM1 mut)–positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication (FLT3-ITD) allele ratio (AR) <0.5 (low AR) has a favorable prognosis, and allogeneic hematopoietic stem cel...

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Published inBlood advances Vol. 2; no. 20; pp. 2744 - 2754
Main Authors Sakaguchi, Masahiro, Yamaguchi, Hiroki, Najima, Yuho, Usuki, Kensuke, Ueki, Toshimitsu, Oh, Iekuni, Mori, Sinichiro, Kawata, Eri, Uoshima, Nobuhiko, Kobayashi, Yutaka, Kako, Shinichi, Tajika, Kenji, Gomi, Seiji, Shono, Katsuhiro, Kayamori, Kensuke, Hagihara, Masao, Kanda, Junya, Uchiyama, Hitoji, Kuroda, Junya, Uchida, Naoyuki, Kubota, Yasushi, Kimura, Shinya, Kurosawa, Saiko, Nakajima, Nana, Marumo, Atsushi, Omori, Ikuko, Fujiwara, Yusuke, Yui, Shunsuke, Wakita, Satoshi, Arai, Kunihito, Kitano, Tomoaki, Kakihana, Kazuhiko, Kanda, Yoshinobu, Ohashi, Kazuteru, Fukuda, Takahiro, Inokuchi, Koiti
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 23.10.2018
American Society of Hematology
Subjects
Myeloid Neoplasia
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Abstract In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation (NPM1 mut)–positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication (FLT3-ITD) allele ratio (AR) <0.5 (low AR) has a favorable prognosis, and allogeneic hematopoietic stem cell transplant (allo-HSCT) in the first complete remission (CR1) period is not actively recommended. We studied 147 patients with FLT3-ITD gene mutation–positive AML, dividing them into those with low AR and those with AR of ≥0.5 (high AR), and examined the prognostic impact according to allo-HSCT in CR1. Although FLT3-ITD AR and NPM1 mut are used in the prognostic stratification, we found that NPM1 mut–positive AML with FLT3-ITD low AR was not associated with favorable outcome (overall survival [OS], 41.3%). Moreover, patients in this group who underwent allo-HSCT in CR1 had a significantly more favorable outcome than those who did not (relapse-free survival [RFS] P = .013; OS P = .003). Multivariate analysis identified allo-HSCT in CR1 as the sole favorable prognostic factor (RFS P < .001; OS P < .001). The present study found that prognosis was unfavorable in NPM1 mut–positive AML with FLT3-ITD low AR when allo-HSCT was not carried out in CR1. •The ELN guideline classifying FLT3-ITD low allele ratio with NPM1 mutation as having a favorable prognosis is questionable.•Performing allo-HSCT during CR1 irrespective of the FLT3-ITD allele ratio and NPM1 mut status significantly improves outcome. [Display omitted]
AbstractList In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation (NPM1 mut)-positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication (FLT3-ITD) allele ratio (AR) <0.5 (low AR) has a favorable prognosis, and allogeneic hematopoietic stem cell transplant (allo-HSCT) in the first complete remission (CR1) period is not actively recommended. We studied 147 patients with FLT3-ITD gene mutation-positive AML, dividing them into those with low AR and those with AR of ≥0.5 (high AR), and examined the prognostic impact according to allo-HSCT in CR1. Although FLT3-ITD AR and NPM1 mut are used in the prognostic stratification, we found that NPM1 mut-positive AML with FLT3-ITD low AR was not associated with favorable outcome (overall survival [OS], 41.3%). Moreover, patients in this group who underwent allo-HSCT in CR1 had a significantly more favorable outcome than those who did not (relapse-free survival [RFS] P = .013; OS P = .003). Multivariate analysis identified allo-HSCT in CR1 as the sole favorable prognostic factor (RFS P < .001; OS P < .001). The present study found that prognosis was unfavorable in NPM1 mut-positive AML with FLT3-ITD low AR when allo-HSCT was not carried out in CR1.In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation (NPM1 mut)-positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication (FLT3-ITD) allele ratio (AR) <0.5 (low AR) has a favorable prognosis, and allogeneic hematopoietic stem cell transplant (allo-HSCT) in the first complete remission (CR1) period is not actively recommended. We studied 147 patients with FLT3-ITD gene mutation-positive AML, dividing them into those with low AR and those with AR of ≥0.5 (high AR), and examined the prognostic impact according to allo-HSCT in CR1. Although FLT3-ITD AR and NPM1 mut are used in the prognostic stratification, we found that NPM1 mut-positive AML with FLT3-ITD low AR was not associated with favorable outcome (overall survival [OS], 41.3%). Moreover, patients in this group who underwent allo-HSCT in CR1 had a significantly more favorable outcome than those who did not (relapse-free survival [RFS] P = .013; OS P = .003). Multivariate analysis identified allo-HSCT in CR1 as the sole favorable prognostic factor (RFS P < .001; OS P < .001). The present study found that prognosis was unfavorable in NPM1 mut-positive AML with FLT3-ITD low AR when allo-HSCT was not carried out in CR1.
In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation (NPM1 mut)–positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication (FLT3-ITD) allele ratio (AR) <0.5 (low AR) has a favorable prognosis, and allogeneic hematopoietic stem cell transplant (allo-HSCT) in the first complete remission (CR1) period is not actively recommended. We studied 147 patients with FLT3-ITD gene mutation–positive AML, dividing them into those with low AR and those with AR of ≥0.5 (high AR), and examined the prognostic impact according to allo-HSCT in CR1. Although FLT3-ITD AR and NPM1 mut are used in the prognostic stratification, we found that NPM1 mut–positive AML with FLT3-ITD low AR was not associated with favorable outcome (overall survival [OS], 41.3%). Moreover, patients in this group who underwent allo-HSCT in CR1 had a significantly more favorable outcome than those who did not (relapse-free survival [RFS] P = .013; OS P = .003). Multivariate analysis identified allo-HSCT in CR1 as the sole favorable prognostic factor (RFS P < .001; OS P < .001). The present study found that prognosis was unfavorable in NPM1 mut–positive AML with FLT3-ITD low AR when allo-HSCT was not carried out in CR1. •The ELN guideline classifying FLT3-ITD low allele ratio with NPM1 mutation as having a favorable prognosis is questionable.•Performing allo-HSCT during CR1 irrespective of the FLT3-ITD allele ratio and NPM1 mut status significantly improves outcome. [Display omitted]
The ELN guideline classifying FLT3 -ITD low allele ratio with NPM1 mutation as having a favorable prognosis is questionable. Performing allo-HSCT during CR1 irrespective of the FLT3 -ITD allele ratio and NPM1 mut status significantly improves outcome. In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation ( NPM1 mut)–positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication ( FLT3 -ITD) allele ratio (AR) <0.5 (low AR) has a favorable prognosis, and allogeneic hematopoietic stem cell transplant (allo-HSCT) in the first complete remission (CR1) period is not actively recommended. We studied 147 patients with FLT3 -ITD gene mutation–positive AML, dividing them into those with low AR and those with AR of ≥0.5 (high AR), and examined the prognostic impact according to allo-HSCT in CR1. Although FLT3 -ITD AR and NPM1 mut are used in the prognostic stratification, we found that NPM1 mut–positive AML with FLT3 -ITD low AR was not associated with favorable outcome (overall survival [OS], 41.3%). Moreover, patients in this group who underwent allo-HSCT in CR1 had a significantly more favorable outcome than those who did not (relapse-free survival [RFS] P = .013; OS P = .003). Multivariate analysis identified allo-HSCT in CR1 as the sole favorable prognostic factor (RFS P < .001; OS P < .001). The present study found that prognosis was unfavorable in NPM1 mut–positive AML with FLT3 -ITD low AR when allo-HSCT was not carried out in CR1.
In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation (NPM1 mut)–positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication (FLT3-ITD) allele ratio (AR) <0.5 (low AR) has a favorable prognosis, and allogeneic hematopoietic stem cell transplant (allo-HSCT) in the first complete remission (CR1) period is not actively recommended. We studied 147 patients with FLT3-ITD gene mutation–positive AML, dividing them into those with low AR and those with AR of ≥0.5 (high AR), and examined the prognostic impact according to allo-HSCT in CR1. Although FLT3-ITD AR and NPM1 mut are used in the prognostic stratification, we found that NPM1 mut–positive AML with FLT3-ITD low AR was not associated with favorable outcome (overall survival [OS], 41.3%). Moreover, patients in this group who underwent allo-HSCT in CR1 had a significantly more favorable outcome than those who did not (relapse-free survival [RFS] P = .013; OS P = .003). Multivariate analysis identified allo-HSCT in CR1 as the sole favorable prognostic factor (RFS P < .001; OS P < .001). The present study found that prognosis was unfavorable in NPM1 mut–positive AML with FLT3-ITD low AR when allo-HSCT was not carried out in CR1.
In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation ( mut)-positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication ( -ITD) allele ratio (AR) <0.5 (low AR) has a favorable prognosis, and allogeneic hematopoietic stem cell transplant (allo-HSCT) in the first complete remission (CR1) period is not actively recommended. We studied 147 patients with -ITD gene mutation-positive AML, dividing them into those with low AR and those with AR of ≥0.5 (high AR), and examined the prognostic impact according to allo-HSCT in CR1. Although -ITD AR and mut are used in the prognostic stratification, we found that mut-positive AML with -ITD low AR was not associated with favorable outcome (overall survival [OS], 41.3%). Moreover, patients in this group who underwent allo-HSCT in CR1 had a significantly more favorable outcome than those who did not (relapse-free survival [RFS] = .013; OS = .003). Multivariate analysis identified allo-HSCT in CR1 as the sole favorable prognostic factor (RFS < .001; OS < .001). The present study found that prognosis was unfavorable in mut-positive AML with -ITD low AR when allo-HSCT was not carried out in CR1.
Author Ueki, Toshimitsu
Nakajima, Nana
Hagihara, Masao
Yui, Shunsuke
Uoshima, Nobuhiko
Oh, Iekuni
Kayamori, Kensuke
Kurosawa, Saiko
Fujiwara, Yusuke
Kobayashi, Yutaka
Uchiyama, Hitoji
Tajika, Kenji
Shono, Katsuhiro
Marumo, Atsushi
Uchida, Naoyuki
Sakaguchi, Masahiro
Fukuda, Takahiro
Kitano, Tomoaki
Kimura, Shinya
Kanda, Junya
Mori, Sinichiro
Usuki, Kensuke
Gomi, Seiji
Kako, Shinichi
Kawata, Eri
Inokuchi, Koiti
Yamaguchi, Hiroki
Kuroda, Junya
Kakihana, Kazuhiko
Omori, Ikuko
Wakita, Satoshi
Ohashi, Kazuteru
Kanda, Yoshinobu
Najima, Yuho
Kubota, Yasushi
Arai, Kunihito
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  organization: Department of Hematology, Nippon Medical School, Tokyo, Japan
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/30341082$$D View this record in MEDLINE/PubMed
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Snippet In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation (NPM1 mut)–positive acute myeloid leukemia (AML) with an fms-like kinase...
In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation ( mut)-positive acute myeloid leukemia (AML) with an fms-like kinase...
In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation (NPM1 mut)-positive acute myeloid leukemia (AML) with an fms-like kinase...
The ELN guideline classifying FLT3 -ITD low allele ratio with NPM1 mutation as having a favorable prognosis is questionable. Performing allo-HSCT during CR1...
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SubjectTerms Myeloid Neoplasia
Title Prognostic impact of low allelic ratio FLT3-ITD and NPM1 mutation in acute myeloid leukemia
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https://dx.doi.org/10.1182/bloodadvances.2018020305
https://www.ncbi.nlm.nih.gov/pubmed/30341082
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