Impact of minimal residual disease, detected by flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia

Abstract

In this retrospective study, we evaluated the impact of pre- and posttransplant minimal residual disease (MRD) detected by multiparametric flow cytometry (MFC) on outcome in 160 patients with ALL who underwent myeloablative allogeneic hematopoietic cell transplantation (HCT). MRD was defined as detection of abnormal B or T cells by MFC with no evidence of leukemia by morphology (<5% blasts in marrow) and no evidence of extramedullary disease. Among 153 patients who had pre-HCT flow data within 50 days before transplant, MRD pre-HCT increased the risk of relapse (hazard ratio (HR) = 3.64; 95% confidence interval (CI), 1.87-7.09; P = .0001) and mortality (HR = 2.39; 95% CI, 1.46-3.90, P = .0005). Three-year estimates of relapse were 17% and 38% and estimated 3-year OS was 68% and 40% for patients without and with MRD pre-HCT, respectively. 144 patients had at least one flow value post-HCT, and the risk of relapse among those with MRD was higher than that among those without MRD (HR = 7.47; 95% CI, 3.30-16.92, P < .0001). The risk of mortality was also increased (HR = 3.00; 95% CI, 1.44-6.28, P = .004). These data suggest that pre- or post-HCT MRD, as detected by MFC, is associated with an increased risk of relapse and death after myeloablative HCT for ALL.

Figure 1

Effect of MRD pre-HCT on transplant outcome. (a) Cumulative incidence of relapse after HCT. One- and 3-year estimates of relapse for patients without MRD pre-HCT were 12% and 17%, respectively, compared to 32% and 38% for patients with MRD pre-HCT. (b) Overall survival after HCT. One- and 3-year estimates of overall survival for patients without MRD pre-HCT were 75% and 68%, respectively, compared to 44% and 40% for patients with MRD pre-HCT. (c) Relapse-free survival. One- and 3-year estimates of relapse-free survival for patients without MRD pre-HCT were 69% and 61%, respectively, compared to 41% and 34% for patients with MRD pre-HCT.

Figure 2

Disease progression after HCT for 17 patients with MRD early post-HCT. Schematic presentation of disease progression of all seventeen patients who were in morphological remission, but with flow cytometry MRD-positive within 50 days posttransplant. Empty circles represent MRD and full circles represent morphological relapse. Rel: relapse; Die: death; A and W: alive and well.