The effect of the detection of minimal residual disease for the prognosis and the choice of post-remission therapy of intermediate-risk acute myeloid leukemia without FLT3-ITD, NPM1 and biallelic CEBPA mutations

Abstract

Background: Intermediate-risk acute myeloid leukemia (IR-AML) without FLT3-ITD, NPM1 and biallelic CEBPA mutations (here referred to as NPM1^mut-negCEBPA^dm-negFLT3-ITD^neg AML) is a clinically heterogeneous disease. The optimal post-remission therapy (PRT) is unclear for patients with NPM1^mut-negCEBPA^dm-negFLT3-ITD^neg AML who achieved first complete response (CR1). This study aims to explore clinical and molecular factors that can help determine the prognosis of those patients and their choice of PRT.

Methods: We retrospectively analyzed 28 patients with NPM1^mut-negCEBPA^dm-negFLT3-ITD^neg AML who received induction chemotherapy and achieved CR1. For PRT, 17 patients received post-remission chemotherapy (PR-CT) and 11 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Results: For patients with NPM1^mut-negCEBPA^dm-negFLT3-ITD^neg AML, multivariate analysis indicated that allo-HSCT and negative minimal residual disease (MRD^neg) before PRT were favorable prognostic factors of overall survival (OS) (allo-HSCT, P = 0.002; MRD^neg, P = 0.018); whereas relapse was an adverse prognostic factor of OS (P = 0.003). Log-rank analysis showed that allo-HSCT significantly improved their OS and RFS compared with PR-CT (OS, P < 0.001; RFS, P = 001). Otherwise, allo-HSCT improved the OS and RFS of patients with NPM1^mut-negCEBPA^dm-negFLT3-ITD^neg AML, whether they obtained MRD^pos or MRD^neg before PRT (OS: MRD^neg, P = 0.036; MRD^pos, P = 0.012; RFS: MRD^neg, P = 0.047; MRD^pos, P = 0.030).

Conclusion: For patients with NPM1^mut-negCEBPA^dm-negFLT3-ITD^neg AML, MRD^neg before PRT and allo-HSCT were favorable prognostic factors of OS. Whether they obtain MRD^neg or not, allo-HSCT is the preferred PRT.

Keywords: Acute myeloid leukemia; Allogeneic hematopoietic stem cell transplantation; CEBPA; FLT3-ITD; Intermediate-risk; Minimal residual disease; NPM1; Post-remission therapy.