Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group

The medium-risk B cell precursor acute lymphoblastic leukemia (ALL) account s for 50-60% of total childhood ALL and comprises the largest number of rel apses still unpredictable with diagnostic criteria. To evaluate the prognos tic impact of minimal residual disease (MRD) in this specific group, a case control study was performed in patients classified and treated as medium ( or intermediate)-risk according to the criteria of national studies (ALL-BF M 90, DCLSG protocol ALL-8, AIEOP-ALL 91), which includes a good day 7 trea tment response. Standardized polymerase chain reaction (PCR) analysis of pa tient-specific immunoglobulin and T cell receptor gene (TCR) rearrangements were used as targets for semiquantitative estimation of MRD levels: greate r than or equal to 10(-2), 10(-3), less than or equal to 10(-4) Twenty-nine relapsing ALL patients were matched with the same number of controls by us ing white blood cell count (WBC), age, sex, and time in first complete remi ssion, as matching factors. MRD was evaluated at time-point 1 (end of proto col Ia of induction treatment, ie 6 weeks from diagnosis) and time-point 2 (before consolidation treatment, ie 3 months from diagnosis). MRD-based hig h risk patients (greater than or equal to 10(-3) at both time-points) were more frequently present in the relapsed cases than in controls (14 vs 2), w hile MRD-based low risk patients (MRD negative at both time-points) (1 vs 1 8) showed the opposite distribution. MRD-based high risk cases experienced a significantly higher relapse rate than all other patients, according to t he estimated seven-fold increase in the odds of failure, and a much higher rate than MRD-based low risk patients (OR = 35.7; P = 0.003). Using the Cox model, the prediction of the relapse-free interval at 4 years was 44.7%, 7 6.4% and 97.7% according to the different MRD categories. MRD-based risk gr oup classification demonstrate their clinical relevance within the medium-r isk B cell precursor ALL which account for the largest number of unpredicta ble relapses, despite the current knowledge about clinical and biological c haracteristics at diagnosis. Therefore, MRD detection during the first 3 mo nths of follow-up can provide the tools to target more intensive therapy to those patients at true risk of relapse.