Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis

摘要

Background: According to the recent National Comprehensive Cancer Network (NCCN) guidelines, the risk level in acute myeloid leukemia (AML) patients with FLT3-ITD and NPM1 double mutation (AML supFLT3-ITD+/NPM1+,/sup ) depends on the allelic ratio of FLT3-ITD . But despite a low or high allelic ratio of FLT3-ITD , AML supFLT3-ITD+/NPM1+,/sup patients belong to the favorable or intermediate risk, for whom allogeneic stem cell transplantation is not obligated. However, some latest studies pointing out that NPM1 and FLT3-ITD double mutation patients showed an inferior prognosis, which have raised concern about the risk categorization and more effective treatment of AML supFLT3-ITD+/NPM1+,/sup patients. Methods: A total of 76 patients were selected for coexisting FLT3 and NPM1 mutations with normal cytogenetics. The prognostic risk factors were analyzed, and treatment strategies including allogeneic stem cell transplantati1on and chemotherapy were compared. Results: In 76 AML supFLT3-ITD+/NPM1+,/sup patients, 36.8% of patients had hyperleukocytosis (HL) and DNMT3A R882 mutation was the most common concomitant gene (23.7%). For 53 patients in the complete remission (CR), 22 had received allogeneic hematopoietic stem cell transplantation (allo-HSCT) on first complete remission (CR1). Patients in transplantation group had better overall survival (OS) and disease-free survival (DFS) than chemotherapy only ( P =0.002 and 0.001, respectively). In multivariable Cox model analyses, HL and DNMT3A R882 mutation were independent adverse prognostic factors (all P 0.05) for AML supFLT3-ITD+/NPM1+,/sup patients. Nevertheless, allo-HSCT was an independent good factor of OS and DFS ( P =0.001 and 0.000; HR =0.173 and 0.138; 95% CI were 0.062–0.483 and 0.049–0.389). And allo-HSCT could moderately improve the poor prognosis of AML supFLT3-ITD+/NPM1+/DNMT3A R882+,/sup. Conclusion: Although, AML supFLT3-ITD+/NPM1+,/sup patients are categorized as favorable or intermediate risk levels according to recent NCCN and ELN guidelines, these patients should receive allo-HSCT in CR1 for a longer survival. AML supFLT3-ITD+/NPM1+,/sup patients with DNMT3A R882 mutation had a very poor prognosis, and allo-HSCT could moderately improve their survival.