PROLONGED PERSISTENCE OF PCR-DETECTABLE MINIMAL RESIDUAL DISEASE AFTER DIAGNOSIS OR FIRST RELAPSE PREDICTS POOR OUTCOME IN CHILDHOOD B-PRECURSOR ACUTE LYMPHOBLASTIC-LEUKEMIA

The follow up of minimal residual disease (MRD) in childhood B-precurs or ALL by polymerase chain reaction (PCR) may be of help for further s tratification of treatment protocols, to improve outcome. However, the clinical relevance of this approach has yet to be defined. We report the retrospective follow-up of MRD in bone marrow (BM) samples from 50 childhood B-precursor ALL patients by IgH/TCR delta PCR. Twenty-two p atients remained in continuous complete remission (median follow-up 61 months), and 28 experienced relapse (median follow-up 75 months). Ini tial regression of MRD on therapy correlated with outcome. At the end of induction therapy 2/18 (11.1%) patients from the CCR group were PCR positive vs 10/16 (62.5%) from the 'relapse' group (P=0.005). The pre sence of PCR detectable WIRD predicted event-free survival independent of standard clinical and cytogenetical parameters. Also subsequent to first BM relapse, a correlation between MRD regression and outcome wa s observed. Six of eight patients who became PCR negative in the time period between relapse and bone marrow transplantation are in CCR, whe reas 7/7 patients who remained PCR positive in this time period died ( P=0.006). In approximately 70% of evaluable patients, clinical relapse was preceded by recurrence of detectable WIRD at time intervals of 3- 18 months earlier and the recurrence of PCR positivity after a period of negativity was always followed by overt relapse. At relapse, the co mbined use of IgH and TCR delta probes reduced false negativity caused by clonal evolution to approximately 10%. This study shows that the e volution of PCR detectable MRD is an independent predictor of outcome.