Minimal residual disease (MRD) positivity at allogeneic hematopoietic cell transplantation, not the quantity of MRD, is a risk factor for relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia

Abstract

Minimal residual disease (MRD) monitoring by quantitative real-time reverse transcription PCR (qRT-PCR) is the standard of care in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). We evaluated the impact of MRD status at hematopoietic cell transplantation (HCT) on relapse, as measured by a unified protocol at a central laboratory. Only patients with Ph-positive ALL who had minor transcripts (e1a2) and who underwent allogeneic HCT in first complete remission between 2008 and 2017 were included. First, patients with negative-MRD (n = 196) and positive-MRD (n = 61) at HCT were analyzed. As expected, MRD positivity at HCT was significantly associated with an increased risk of hematological relapse (hazard ratio [HR], 2.91; 95% CI 1.67-5.08; P < 0.001) in the multivariate analysis. Next, patients with positive-MRD were divided into low-MRD (n = 39) and high-MRD (n = 22) groups. In the multivariate analysis, high-MRD at HCT was not significantly associated with an increased risk of hematological relapse compared to the low-MRD group (HR 1.10; 95% CI 0.54-2.83; P = 0.620). These results indicate that the therapeutic decisions should be made based on MRD positivity, rather than on the MRD level, at HCT.