Measurable residual disease of acute lymphoblastic leukemia in allograft settings: how to evaluate and intervene

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curable strategy for acute lymphoblastic leukemia (ALL), especially for adult cases. However, leukemia relapse after allograft restricts the improvement of transplant outcomes. Measurable residual disease (MRD) has been the strongest predictor for relapse after allo-HSCT, allowing MRD-directed preemptive therapy.

This manuscript summarizes the detection of MRD in patients with ALL who undergo allo-HSCT, focusing the effects of positive pre-HSCT MRD and post-HSCT MRD on outcomes as well as MRD-directed interventions.

Except for MFC and RQ-PCR, other strategies, such as next-generation sequencing and RNAseq, have been developed for MRD determination. Negative effects of positive MRD peri-transplantation on outcomes of ALL patients were observed both in human leukocyte antigen (HLA)-matched sibling donor transplantation and in alternative donor transplantation. Advances have been made in determining the need for transplant according to MRD evaluation after induction or consolidation therapy. A number of approaches, including CAR-T-cell therapy, antibodies (blinatumomab, etc), targeted therapy (imatinib, etc), transplant donor selection, as well as donor lymphocyte infusion and interferon-α, have been successfully used or are promising for peri-transplantation MRD interventions. This progress could lead to the significant improvement of transplant outcomes for ALL patients.