MINIMAL RESIDUAL DISEASE STATUS BEFORE ALLOGENEIC BONE-MARROW TRANSPLANTATION IS AN IMPORTANT DETERMINANT OF SUCCESSFUL OUTCOME FOR CHILDREN AND ADOLESCENTS WITH ACUTE LYMPHOBLASTIC-LEUKEMIA

The efficacy of allografting in acute lymphoblastic leukemia (ALL) is heavily influenced by remission status at the time of transplant. Usin g polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis, we have investigated retrospectively the impact of submicro scopic leukemia on outcome in 64 patients receiving allogeneic bone ma rrow transplantation (BMT) for childhood ALL. Remission BM specimens w ere taken 6 to 81 days (median, 23) before transplant. All patients re ceived similar conditioning therapy; 50 received grafts from unrelated donors and 14 from related donors. Nineteen patients were transplante d in first complete remission (CR1) and 45 in second or subsequent CR. MRD was analyzed by PCR of Ig or T-cell receptor delta or gamma rearr angements, electrophoresis, and allele-specific oligoprobing, Samples were rated high-level positive (clonal band evident after electrophore sis; sensitivity 10(-2) to 10(-3)), low-level positive (MRD detected o nly after oligoprobing; sensitivity 10(-3) to 10(-5)), or negative. Ex cluding 8 patients transplanted in CR2 for isolated extramedullary rel apse (all MRD-), MRD was detected at high level in 12 patients, low le vel in 11, and was undetectable in 33, Two-year event-free survival fo r these groups was 0%, 36%, and 73%, respectively (P < .001), Follow-u p in patients remaining in continuing remission is 20 to 96 months (me dian, 35), These results suggest that MRD analysis could be used routi nely in this setting. This would allow identification of patients with resistant leukemia (who may benefit from innovative BMT protocols) an d of those with more responsive disease (who may be candidates for ran domized trials of BMT versus modern intensive relapse chemotherapy). ( C) 1998 by The American Society of Hematology.