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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

Marta Pratcorona, Salut Brunet, Josep Nomdedéu, Josep Maria Ribera, Mar Tormo, Rafael Duarte, Lourdes Escoda, Ramon Guàrdia, M. Paz Queipo de Llano, Olga Salamero, Joan Bargay, Carmen Pedro, Josep Maria Martí, Montserrat Torrebadell, Marina Díaz-Beyá, Mireia Camós, Dolors Colomer, Montserrat Hoyos, Jorge Sierra and Jordi Esteve

Key points

  • In intermediate risk AML, effect of FLT3 burden is modulated by NPM1 mutation, especially in patients with a low ratio.

  • Combined evaluation of NPM1 mutation and FLT3-ITD burden might contribute to identify patients who benefit from early allogeneic HSCT

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 allelic burden in 303 patients with de novo intermediate-risk cytogenetics AML treated in CETLAM trials. Outcome of patients was analyzed according to FLT3-ITD/FLT3 wild-type (FLT3wt) ratio and NPM1 mutation (NPM1mut). 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 RR and shortened OS 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.

  • Submitted June 5, 2012.
  • Accepted January 22, 2013.