Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia after first relapse

Using flow cytometric techniques capable of detecting 0.01% leukemic cells, we prospectively studied minimal residual disease (MRD) in patients with acute lymphoblastic leukemia (ALL) after first relapse. At the end of remission reinduction, 41 patients had a bone marrow sample adequate for MRD studies; 35 of these were in morphologic remission. Of the 35 patients, 19 (54%) had MRD greater than or equal to0.01%, a finding that was associated with subsequent leukemia relapse. The 2-year cumulative incidence of second leukemia relapse was 70.2 +/- 12.3% for the 19 MRD-positive patients and 27.9 +/- 12.4% for the 16 MRD-negative patients ( P = 0.008). Among patients with a first relapse off therapy, 2-year second relapse rates were 49.1 +/- 17.8% in the 12 MRD-positive and 0% in the 11 MRD-negative patients ( P = 0.014); among those who received only chemotherapy after first relapse, the 2-year second relapse rates were 81.5 +/- 14.4% ( n = 12) and 25.0 +/- 13.1% ( n = 13), respectively ( P = 0.004). Time of first relapse and MRD were the only two significant predictors of outcome in a multivariate analysis. We conclude that MRD assays should be used to guide the selection of postremission therapy in patients with ALL in first relapse.