Bone marrow transplantation from alternative donors for thalassemia: HLA-phenotypically identical relative and HLA-nonidentical sibling or parent transplants

Twenty-nine patients with thalassemia and a median age of 6 years (range 1. 1-33 years) were given a BMT from an alternative donor. Six of the 29 donor s were HLA-phenotypically identical and two were mismatched relatives, 13 w ere mis-matched siblings and eight were mismatched parents. Six patients re ceived no antigen (relatives), 15 patients one antigen, five patients two a ntigen and three patients three antigen disparate grafts. Twenty-three pati ents were in class 2 or class 3, whereas six patients were in class 1, Thir teen patients were given BUCY, nine patients BUCY plus ALG, six patients BU CY plus TBI or TLI and one patient BUCY with prior cytoreductive-immunosupp ressive treatment as conditioning, As GVHD prophylaxis four patients receiv ed MTX, 22 CsA + MTX + methylprednisolone (MP) and three patients CsA + MP, Thirteen of 29 patients (44.8%) had sustained engraftment. The probability of graft failure or rejection was 55%, There were no significant differenc es between antigen disparities and graft failure. The incidence of grade II -IV acute GVHD was 47.3% and chronic GVHD was 37.5%. The incidence of acute GVHD was higher in patients receiving one or two antigen disparate in the GVHD direction grafts (vs no antigen) (P EQ 0.04; odds ratio 10.8; 95% CI 1 .5-115). The probability of overall and event-free survival was 65% and 21% , respectively, with median follow-up of 7.5 years (range 0.6-17 years) for surviving patients. The degree of HLA disparity between patient and donor did not have a significant effect on survival. The incidence of nonhematolo gic toxicity was low. Transplant-related mortality was 34%. GVHD (acute or chronic) was a major contributing cause of death (50%) followed by infectio ns (30%), We conclude that at present, due to high graft failure and GVHD r ates, BMT from alternative donors should be restricted to patients who have poor life expectancies because they cannot receive adequate conventional t reatment or because of alloimmunization to minor blood antigens.