MOLECULAR-DETECTION OF MINIMAL RESIDUAL DISEASE IN ADULT AND CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA REVEALS DIFFERENCES IN TREATMENT RESPONSE

Immunoglobulin heavy chain gene (IgH gene) rearrangements are found in the majority of patients with B lineage acute lymphoblastic leukaemia (ALL). Two hundred and three bone marrow samples from 54 patients (33 adults and 21 children) were analysed by PCR within specific time-poi nts after diagnosis tie 1, 2-3, 4-6 and 7-12 months) using FR1 and JH primers (fingerprinting with a sensitivity greater than or equal to 1: 5x10(3)). CDR3-derived allele specific oligoprimers (ASO to achieve a sensitivity between 1:10(4) and 1:10(5)) were applied to 12 children a nd 18 adults, while size of CDR3 region, oligoclonality and background problems prevented their application to the remaining patients. All p atients were followed clinically for greater than or equal to 24 month s. Thirty adults and 16 children presented as newly diagnosed ALL, whi le the remaining eight patients were analysed in first or subsequent r elapse. Patients destined to relapse showed a higher proportion of pos itive tests (greater than or equal to 50%), particularly after 1 month , than in the remission group, irrespective of age. Among patients sta ying in remission, a decrease in MRD-positive tests occurred during th e first 12 months in both age groups. However, the proportion of posit ive tests dropped below 15% at a later stage in adults (4-6 months) th an in children (2-3 months). Among children, only patients destined to relapse were BARD positive beyond 1 month, with the exception of only one patient, still positive at 2-3 months in the remission group. The difference in MRD positivity between relapse and remission patients w as statistically significant in children (P < 0.03) at any time of tes ting, but only at 4-6 months in adults (P < 0.01). These data suggest that resolution of MRD in ALL occurs more rapidly in children compared to adults, particularly within the first 6 months. Children and adult s, studied in first or subsequent relapse, showed a higher proportion of positive tests during reinduction compared to newly diagnosed patie nts.