title: [Prognostic significance of early assessment of minimal residual disease in acute myeloid leukemia with mutated NPM1 patients].
abstract: Objective:To explore prognostic significance of early assessment of minimal residual leukemia (MRD) in adult patients withde novoacute myeloid leukemia (AML) with mutated NPM1.Methods:The response, NPM1 mutated transcript level after induction chemotherapy and the first 2 cycles of consolidation chemotherapy, disease-free survival (DFS) and overall survival (OS) in 137 patients with AML with NPM1 mutations of A, B and D were retrospectively analyzed.Results:Data of 137 patients were collected, 67 were male, the median age was 49 years (16-67 years) , 107 (78.1%) had normal karyotype, 57 (41.6%) had positive FLT3-ITD mutation, the median NPM1 mutated transcript level at diagnosis was 84.1%. Among the 134 evaluable patients, 115 (85.8%) achieved a complete remission (CR) . Multivariate analyses revealed that WBC<100×10(9)/L (OR=0.3, 95%CI0.1-0.9,P=0.027) and first induction therapy with "IA10" protocol (OR=0.3, 95%CI0.1-0.8,P=0.015) were factors associated with achieving a CR. With a median follow-up period of 24 months (range, 2 to 91 months) in 77 survived CR patients, the probabilities of DFS and OS at 3 years were 48.0% and 63.9%, respectively. Multivariate analyses showed that positive FLT3-ITD (HR=3.2, 95%CI1.6-6.7,P=0.002) , high MRD level after 2 cycles of consolidation chemotherapy (NPM1 mutation transcript level <3-log reduction from the individual baseline,HR=23.2, 95%CI7.0-76.6,P<0.001) and chemotherapy or autologous hematopoietic stem cell transplantation (auto-HSCT) rather than allogeneic HSCT (allo-HSCT) (HR=2.6, 95%CI1.0-6.6,P=0.045) were the unfavorable factors affecting DFS, high MRD level at the time of achieving the first CR (NPM1 mutation transcript level <2-log reduction from the individual baseline,OR=2.5, 95%CI1.0-6.1,P=0.040) and after 2 cycles of consolidation chemotherapy (HR=4.5, 95%CI2.0-10.3,P<0.001) were the unfavorable factors affecting OS. Furthermore, DFS and OS rates at 3 years in those receiving chemotherapy or auto-HSCT were 39.7% and 59.1%, respectively; positive FLT3-ITD and high MRD level after 2 cycles of consolidation chemotherapy were independent factors associated with both shorter DFS (HR=3.5, 95%CI1.6-7.6,P=0.002 andHR=8.9, 95%CI3.8-20.7,P<0.001) and OS (HR=2.7, 95%CI1.1-6.9,P=0.036 andHR=3.1, 95%CI1.2-8.0,P=0.021) ; meanwhile, high MRD level at the time of achieving the first CR associated with shorter OS (HR=3.1, 95%CI1.2-8.0,P=0.022) .Conclusion:Positive FLT3-ITD mutation and high MRD level after induction or consolidation chemotherapy associated with poor outcomes in AML patients with mutated NPM1.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
authors.forename: T
authors.initials: T
authors.lastname: Zhao
authors.forename: H H
authors.initials: HH
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: J S
authors.initials: JS
authors.lastname: Jia
authors.forename: S M
authors.initials: SM
authors.lastname: Yang
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: L P
authors.initials: LP
authors.lastname: Xu
authors.forename: X H
authors.initials: XH
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Jiang
authors.forename: G R
authors.initials: GR
authors.lastname: Ruan
authors.forename: D B
authors.initials: DB
authors.lastname: Wang
authors.forename: X J
authors.initials: XJ
authors.lastname: Huang
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D014182:Transplantation, Autologous; D055815:Young Adult
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin
keywords: Gene, NPM1; Leukemia, myeloid, acute; Minimal residual disease; Prognosis