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  • Title: Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy.
    Author: Pratcorona M, Brunet S, Nomdedéu J, Ribera JM, Tormo M, Duarte R, Escoda L, Guàrdia R, Queipo de Llano MP, Salamero O, Bargay J, Pedro C, Martí JM, Torrebadell M, Díaz-Beyá M, Camós M, Colomer D, Hoyos M, Sierra J, Esteve J, Grupo Cooperativo Para el Estudio y Tratamiento de las Leucemias Agudas Mieloblásticas.
    Journal: Blood; 2013 Apr 04; 121(14):2734-8. PubMed ID: 23377436.
    Abstract:
    Risk associated to FLT3 internal tandem duplication (FLT3-ITD) in patients with acute myeloid leukemia (AML) may depend on mutational burden and its interaction with other mutations. We analyzed the effect of FLT3-ITD/FLT3 wild-type (FLT3wt) ratio depending on NPM1 mutation (NPM1mut) in 303 patients with intermediate-risk cytogenetics AML treated with intensive chemotherapy. Among NPM1mut patients, FLT3wt and low ratio (<0.5) subgroups showed similar overall survival, relapse risk, and leukemia-free survival, whereas high ratio (≥0.5) patients had a worse outcome. In NPM1wt AML, FLT3-ITD subgroups showed a comparable outcome, with higher risk of relapse and shortened overall survival than FLT3wt patients. Allogeneic stem cell transplantation in CR1 was associated with a reduced relapse risk in all molecular subgroups with the exception of NPM1mut AML with absent or low ratio FLT3-ITD. In conclusion, effect of FLT3 burden is modulated by NPM1 mutation, especially in patients with a low ratio.
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