Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia

By using rapid flow cytometric techniques capable of detecting one leukemic cell in 10(4) normal cells, we prospectively studied minimal residual dise ase (MRD) in 195 children with newly diagnosed acute lymphoblastic leukemia (ALL) in clinical remission. Bone marrow aspirates (n = 629) were collecte d at the end of remission induction therapy and at 3 intervals thereafter. Detectable MRD tie, greater than or equal to 0.01% leukemic mononuclear cel ls) at each time point was associated with a higher relapse rate (P <.001); patients with high levels of MRD at the end of the induction phase (greate r than or equal to 1%) or at week 14 of continuation therapy (greater than or equal to 0.1%) had a particularly poor outcome. The predictive strength of MRD remained significant even after adjusting for adverse presenting fea tures, excluding patients at very high or very low risk of relapse from the analysis, and considering levels of peripheral blood lymphoblasts at day 7 and day 10 of induction therapy. The incidence of relapse among patients w ith MRD at the end of the induction phase was 68% +/- 16% (SE) if they rema ined with MRD through week 14 of continuation therapy, compared with 7% +/- 7% if MRD became undetectable (P =.035). The persistence of MRD until week 32 was highly predictive of relapse (all 4 MRD+ patients relapsed vs 2 of the 8 who converted to undetectable MRD status; P=.021). Sequential monitor ing of MRD by the method described here provides highly significant, indepe ndent prognostic information in children with ALL. Recent improvements in t his flow cytometric assay have made it applicable to more than 90% of all n ew patients. (Blood. 2000;96:2691-2696) (C) 2000 by The American Society of Hematology.