Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post …

M Pratcorona, S Brunet, J Nomdedéu… - Blood, The Journal …, 2013 - ashpublications.org
M Pratcorona, S Brunet, J Nomdedéu, JM Ribera, M Tormo, R Duarte, L Escoda, R Guardia…
Blood, The Journal of the American Society of Hematology, 2013ashpublications.org
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 (FLT3 wt) ratio depending on
NPM1 mutation (NPM1mut) in 303 patients with intermediate-risk cytogenetics AML treated
with intensive chemotherapy. Among NPM1 mut patients, FLT3 wt and low ratio (< 0.5)
subgroups showed similar overall survival, relapse risk, and leukemia-free survival, whereas …
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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