Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia

Abstract

Background and objectives: The molecular analysis of minimal residual disease (MRD) may provide information on the risk of recurrence in patients with acute lymphoblastic leukemia (ALL). The aim of this study was to correlate the kinetics of MRD clearance after allogeneic transplantation with the clinical outcome of adults with ALL.

Design and methods: MRD was evaluated by real-time quantitative polymerase chain reaction (RQ-PCR) using probes derived from fusion chimeric genes (BCR/ABL and MLL/AF4) (n=22) or rearrangements of the T-cell receptor or immunoglobulin genes (n=21). Forty-three adult patients with ALL were studied to correlate the kinetics of MRD clearance before and after allogeneic hematopoietic stem cell transplantation.

Results: At 36 months, the overall survival of patients who underwent transplantation in hematologic remission (n= 37) was 80% for those who were PCR-negative before transplantation (n= 12) compared to 49% for PCR-positive patients (n= 25)(p=0.17). For the same patients the cumulative incidence of relapse was 0% and 46%, respectively (p=0.027). Moreover, the relapse rate of patients who were PCR-negative at day +100 after transplantation was remarkably low (7%) compared to that among patients who were PCR-positive (80%, p=0.0006).

Interpretation and conclusions: The kinetics of MRD clearance may help to identify patients at high risk of leukemia relapse after allogeneic stem cell transplantation. Patients not achieving an early molecular remission after transplantation require prompt and appropriate pre-emptive treatments such as infusions of donor lymphocytes or new experimental drugs.