UNRELATED DONOR BONE-MARROW TRANSPLANTS IN CHILDREN

Only a small proportion of children who might benefit from bone marrow transplant (BMT) have an HLA-identical sibling. To provide this poten tially curative therapy to patients without a matched related donor, m arrow transplants using less well matched related donors or unrelated donors (identified through computerized donor registries) have been pe rformed. We report the outcome of 24 consecutive unrelated donor BMT's performed on children. Eligible diagnosis included acute leukemia (AL ) (n = 15), chronic myelogenous leukemia (CML) (n = 4), myelodysplasti c syndrome (MDS) (n = 3), and severe aplastic anemia (SAA) (n = 2). Al l donor/recipient pairs were sere-matched at 5 or 6 of the 6 HLA A, B, and DR antigens. Several different preparative regimens were used, bu t fractionated total body irradiation (TBI) was used in 20 patients. A ll recipients received graft-versus-host-disease (GVHD) prophylaxis wi th cyclosporine-A (CSA), four with short course methotrexate (MTX), 14 in combination with short course MTX and methylprednisolone (MPS), an d five in combination with a mouse monoclonal antibody to CD5, coupled to the A-chain of ricin Xomazyme-65). One patient received CSA and MP S alone after a T-cell depleted marrow transplant. Twenty of 23 evalua ble recipients engrafted (87%). Two patients with CML never engrafted and had autologous marrow recovery, one patient with SAA died at 128 d ays without evidence of engraftment, and there was one early death at day + 9. Fourteen of 20 patients (70%) with stable donor-derived hemat opoiesis developed significant acute GVHD greater than or equal to gra de II). Eleven of 15 engrafted patients who survived > 100 days after BMT developed chronic GVHD (73%). Thirteen patients survive, 10 diseas e-free; 2 yr actuarial survival and disease-free survival are 47% and 41%, respectively. Of the 19 engrafted patients with leukemia or MDS, only three have relapsed. The actuarial relapse risk at 2 yr is 24%. U nrelated donor transplants in children are associated with an increase d risk of GVHD and nonengraftment compared to matched sibling transpla nts. Increased donor age is significantly associated with a greater ri sk of acute GVHD.