Molecular MRD status and outcome after transplantation in NPM1-mutated AML

Area of Science:

• Hematology
• Oncology
• Stem Cell Transplantation

Background:

• Relapse is a primary cause of treatment failure in acute myeloid leukemia (AML) post-allogeneic stem cell transplantation (alloSCT).
• Pre-transplant measurable residual disease (MRD) is a known relapse predictor, but its impact using sensitive molecular assays requires further clarification.

Purpose of the Study:

• To evaluate the prognostic significance of pre-transplant molecular MRD levels in NPM1-mutant AML patients undergoing alloSCT.
• To assess the combined prognostic value of MRD levels and FLT3-ITD mutations.
• To investigate the impact of T-depletion on survival outcomes in this patient cohort.

Main Methods:

• Analysis of pre-transplant blood and bone marrow samples using reverse-transcription polymerase chain reaction for MRD detection.
• 107 patients with NPM1-mutant AML from the UK National Cancer Research Institute AML17 study were included.
• Kaplan-Meier survival analysis and Cox proportional hazards modeling were used to assess outcomes.

Main Results:

• Pre-transplant MRD levels were highly prognostic for 2-year overall survival (2y-OS): negative (83%), low (63%), and high (13%).
• Patients with low-level MRD and FLT3-ITD had significantly poorer outcomes (HR, 6.14; P = .01).
• Combining MRD and FLT3-ITD status created two distinct prognostic groups (2y-OS 17% vs 82%).
• T-depletion was associated with reduced survival in the overall cohort and MRD-positive patients (HRs 3.24 and 3.78, respectively).

Conclusions:

• Pre-transplant molecular MRD assessment is a critical prognostic factor in NPM1-mutant AML patients undergoing alloSCT.
• The combination of MRD levels and FLT3-ITD status provides robust risk stratification.
• T-depletion strategies should be carefully considered due to their negative impact on survival in MRD-positive patients.