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.
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.
authors: Hematology Department, Hospital Clínic, Institut d'investigacions biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors: Marta
authors: M
authors: Pratcorona
authors: Salut
authors: S
authors: Brunet
authors: Josep
authors: J
authors: Nomdedéu
authors: Josep Maria
authors: JM
authors: Ribera
authors: Mar
authors: M
authors: Tormo
authors: Rafael
authors: R
authors: Duarte
authors: Lourdes
authors: L
authors: Escoda
authors: Ramon
authors: R
authors: Guàrdia
authors: M Paz
authors: MP
authors: Queipo de Llano
authors: Olga
authors: O
authors: Salamero
authors: Joan
authors: J
authors: Bargay
authors: Carmen
authors: C
authors: Pedro
authors: Josep Maria
authors: JM
authors: Martí
authors: Montserrat
authors: M
authors: Torrebadell
authors: Marina
authors: M
authors: Díaz-Beyá
authors: Mireia
authors: M
authors: Camós
authors: Dolors
authors: D
authors: Colomer
authors: Montserrat
authors: M
authors: Hoyos
authors: Jorge
authors: J
authors: Sierra
authors: Jordi
authors: J
authors: Esteve
mesh_terms: D000328:Adult; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D020440:Gene Duplication; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors; D055502:Secondary Prevention; D020080:Tandem Repeat Sequences; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3