A PROSPECTIVE-STUDY OF MINIMAL RESIDUAL DISEASE IN CHILDHOOD B-LINEAGE ACUTE LYMPHOBLASTIC-LEUKEMIA - MRD LEVEL AT THE END OF INDUCTION IS A STRONG PREDICTIVE FACTOR OF RELAPSE

We prospectively investigated minimal residual disease (MRD) in 51 chi ldren with B-lineage acute lymphoblastic leukaemia (ALL) treated accor ding to the Fralle 93 protocol. PCR follow-up was performed in childre n in morphological and cytogenetic complete remission, provided an imm unoglobulin (IgH) gene rearrangement could be detected using FR3/J(H) amplimers. MRD was studied according to our previously described metho dology, with a few modifications including the use of a consensus J(H) probe to control for PCR efficiency variations. Out of the initial 51 patients, 34 were assessable for MRD at the end of induction at the t ime of analysis. MRD levels were as follows: >1/10(3) in 26%, 1/10(3) to 1/10(4) in 50% and <1/10(4) or not detectable in 24%. With a median follow-up of 20 months there were five relapses, all of which occurre d in the group of patients with MRD >1/10(3). To date, none of the pat ients with MRD less than or equal to 1/10(3) (good molecular responder ) has relapsed. Classification according to molecular response at the end of induction did not correlate with the conventional risks groups: there were no statistically significant differences between good and bad molecular responders. Of particular interest is the absence of cor relation between WBC al diagnosis and MRD level at the end of inductio n. We conclude that classification of patients into good slid bad mole cular responders using PCR set ms to be a better prognostic indicator than conventional risk factors in childhood B-lineage ALL. Patients wi th MRD level >1/10(3) have a particularly poor outcome and should alwa ys be considered for alternative therapeutic strategies in the future, whereas in good molecular responders belonging to poor or intermediat e risk categories, treatment de-escalation might be contemplated.