Pretransplantation minimal residual disease monitoring by multiparameter flow cytometry predicts outcomes of AML patients receiving allogeneic hematopoietic stem cell transplantation

Abstract

Background and purpose: Is minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) prognostic for acute myeloid leukemia (AML) patients before allogeneic hemopoietic stem cell transplantation (allo-HSCT)? And if so, what level of MRD eradication can be used to help guide the timing of HSCT? Can haplo-HSCT improve the prognosis of AML patients with MRD positive? To figure out these questions, we initiated this retrospective study.

Methods: 96 AML patients were included retrospectively and divided into 5 groups, according to pre-transplantation MRD levels (from 5 × 10^-2 to <1 × 10^-4), to analyze the overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR). Secondly, we compared the prognosis of MRD-negative (MRD^neg) and MRD-positive (MRD^pos) AML patients (cutoff value = 1 × 10^-3) who underwent allo-HSCT, and further analyzed the prognosis of MRD^pos patients after received different transplantation modalities.

Results: It is found that the 2-year OS and DFS of MRD negative group were better than the MRD positive group, and that the deeper the eradication of MRD before transplantation, the better the prognosis of patients. The CIR in patients received HLA-identical transplantation, was higher in the MRD^pos than in the MRD^neg. Haploid transplantation reduced the CIR disparity between MRD^pos and MRD^neg group. Subsequently, in AML patients who remain MRD positive before HSCT, we show that haplo-HSCT offered a better prognosis than HLA-identical transplantation (MSDT and MUDT).

Conclusion: It is suggested that achieving MFC-MRD <10^-3 (10^-4 or even better) before allo-HSCT could reduce the relapse of AML and improve OS and DFS significantly, while haplo-HSCT may be preferred for patients not achieving MRD negativity.

Keywords: Acute myeloid leukemia/AML; Allogeneic hemopoietic stem cell transplantation/allo-HSCT; Haploidentical hematopoietic stem cell transplantations/haplo-HSCT; Minimal residual disease/MRD; Prognosis.