A PHASE-II TRIAL OF PARTIALLY INCOMPATIBLE BONE-MARROW TRANSPLANTATION FOR HIGH-RISK ACUTE LYMPHOBLASTIC-LEUKEMIA IN CHILDREN - PREVENTION OF GRAFT-REJECTION WITH ANTI-LFA-1 AND ANTI-CD2 ANTIBODIES

Bone marrow transplantation (BMT) from matched sibling donors has been useful for the treatment of acute lymphoblastic leukaemia in children with a poor prognosis but is not available to more than two-thirds of patients who do not have a matched allogeneic donor. This study was u ndertaken to assess one strategy of marrow graft rejection prevention when alternative marrow sources such as HLA-phenoidentical unrelated v olunteers and HLA-partially incompatible relatives were used. Results have been compared with two matched groups of children with the same r isks factors and disease status who underwent HLA-genoidentical or aut ologous BMT. The conditioning regimen was the same for the three group s of patients; in the study group anti-LFA-1 and anti-CD2 monoclonal a ntibodies combined with T-cell depletion of the marrow was added to pr event graft rejection and graft-versus-host disease. Nineteen patients were included and followed for a median of 25 months (14 months to 3 years). Bone marrow engraftment occurred in 83% of the evaluable patie nts. Post-transplantation infectious diseases were the most frequent c auses of death in the study group, occurring in 31% of patients. No fa tal infections occurred in the two control groups. Post-transplantatio n relapse of leukaemia occurred in 26% of study group's patients, in 5 8% of autologous BMT control group's patients and in 5% of HLA-genoide ntical allogeneic group's patients. The event-free survival was 83% in the HLA-genoidentical control group, and 30% and 24% in the study gro up and in the autologous control group, respectively. In conclusion, a high rate of engraftment was achieved by the use of anti-LFA-1 and an ti-CD2 antibodies. Occurrence of a long-lasting immunodeficiency, howe ver, led to a high incidence of lethal infections and relapses. Combin ed approaches are therefore to be investigated accelerating immune rec onstitution after transplantations of T-depleted HLA partially incompa tible marrow.