Minimal residual disease-based augmented therapy in childhood acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group.

Background The majority of minimal residual disease (MRD) positive patients with acute lymphoblastic leukemia (ALL) hive poor outcomes The ALL2000 study was performed to evaluate the efficacy of augmented chemotherapy based on MRD restratification in child hood ALL Procedure Between 2000 and 2004 305 eligible patients with precursor B or T cell ALL were enrolled in the ALL2000 study The ALL941 based therapy protocol utilized PCR MRD assays using Immunoglobulin and T cell receptor gene rearrangements They were initially stratified into three risk groups according to leukocyte count and age and MRD levels were measured at weeks 5 (TP1) and 12 (TP2) for a second stratification From week 14 patients with MRD levels >= 10(-3) received an increase in therapy (one risk group higher) while the remainder continued to receive the initial risk adapted therapy Results The overall 5 year event free survival (EFS) rate for ALL2000 was 79 7 +/- 2 4% MRD stratification was feasible for 234 of 301 patients (77%) who achieved complete remission The EFS rite of the MRD stratifiable (MRD) group was 82 5 +/- 2 6% consider ably superior to the 74 7 +/- 5 7% of MRD non stratifiable (Non MRD) group (P = 0 084) and the 74 4 +/- 2 1% for ALL 941 (P = 0 012) MRD positive patients at TP2 showed inferior outcomes as compared with MRD negative cases but the difference did not reach statistically significant level in any risk groups or immunophenotypes Conclusions These results suggest that augmented therapy for MRD positive patients at TP2 contributed to better outcomes of the ALL2000 study Pediatr Blood Cancer 2010 55 1287-1295 (C) 2010 Wiley Liss Inc