Patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) achieving complete remission (CR) before allogeneic hematopoietic stem-cell transplantation (alloHSCT) exhibit varying survival outcomes depending on their measurable residual disease (MRD) status. A recent study underscores the prognostic significance of pre-transplant MRD assessment using multiparametric flow cytometry (MFC) and molecular PCR techniques.
The monocentric retrospective study, spanning from January 2000 to December 2020, included 192 patients. With a median follow-up of 77 months, the research team assessed the impact of pre-transplant MRD status on survival outcomes. The results demonstrated a significant difference in overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR) between MRD-negative and MRD-positive patients undergoing alloHSCT in CR.
Impact of MRD Status on Survival
MRD-negative patients demonstrated a median OS of 130.6 months compared to 16.0 months for MRD-positive patients (P < 0.001). Similarly, the median DFS was 109.6 months for MRD-negative patients versus 7.1 months for MRD-positive patients (P < 0.001). The 12-month CIR was 7.3% in MRD-negative patients and 33.7% in MRD-positive patients (P < 0.0001).
Methodological Considerations
The study emphasized the importance of combining MFC and molecular PCR-based techniques for MRD assessment. Discordant results between the two methods were associated with intermediate DFS, highlighting the need for a comprehensive approach. MRD-negative status, as determined by molecular PCR, WT1 overexpression, and MFC, correlated with longer median DFS compared to MRD-positive status (P = 0.001, P < 0.001, P < 0.001, respectively).
Subgroup Analysis
Further analysis revealed that MRD-positive patients within the ELN2017 adverse-risk category (P < 0.0001), those undergoing myeloablative and reduced-intensity conditioning regimens (P < 0.0001, P = 0.005), patients younger than 60 years (P < 0.001), and AML patients (P < 0.001) experienced lower DFS. This difference was not observed in patients aged 60 years or older (P = 0.27) or in MDS patients (P = 0.70). MRD-positive patients within the favorable/intermediate ELN2017 category trended toward lower DFS (P = 0.05).
Clinical Implications
The findings reinforce the critical role of pre-transplant MRD status as a robust prognostic indicator for OS, DFS, and CIR in AML and MDS patients. Integrating both MFC and molecular PCR techniques for MRD assessment is essential, as discrepancies between methods can significantly influence patient outcomes and treatment strategies. These results may help refine risk stratification and inform post-transplant management decisions.
