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

• Published in: Blood Vol. 121; no. 14; pp. 2734 - 2738
• Main Authors: Pratcorona, Marta, Brunet, Salut, Nomdedéu, Josep, Ribera, Josep Maria, Tormo, Mar, Duarte, Rafael, Escoda, Lourdes, Guàrdia, Ramon, Queipo de Llano, M. Paz, Salamero, Olga, Bargay, Joan, Pedro, Carmen, Martí, Josep Maria, Torrebadell, Montserrat, Díaz-Beyá, Marina, Camós, Mireia, Colomer, Dolors, Hoyos, Montserrat, Sierra, Jorge, Esteve, Jordi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.04.2013
• Subjects: Adult; Alleles; Antineoplastic Agents - therapeutic use; Disease-Free Survival; Female; fms-Like Tyrosine Kinase 3 - genetics; Gene Duplication; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - therapy; Male; Middle Aged; Nuclear Proteins - genetics; Prognosis; Remission Induction; Risk Factors; Secondary Prevention; Tandem Repeat Sequences; Treatment Outcome
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2012-06-431122

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. •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.