BONE-MARROW TRANSPLANTATION FOR SEVERE APLASTIC-ANEMIA FROM GENOTYPICALLY HLA-NONIDENTICAL RELATIVES - AN UPDATE OF THE SEATTLE EXPERIENCE

This report updates the results of marrow transplantation at the Fred Hutchinson Cancer Research center for patients with severe aplastic an emia whose donors were HLA-nonidentical relatives. Between 1970 and 19 93, 40 patients received transplants for severe aplastic anemia from r elated donors other than HLA genotypically matched siblings, Nine pati ents (group 1) were conditioned with cyclophosphamide (Cy) at 50 mg/kg for 4 doses and received marrow from phenotypically HLA-matched relat ives, With the exception of one accidental death, all patients are ali ve and disease free 3-18 years after transplantation. Thirty-one patie nts received marrow from HLA-mismatched relatives who differed by one or more loci, Fifteen of these patients (group 2) received Cy at 50 mg /kg for 4 doses without total body irradiation (TBI) and none survived , Because of failure to sustain engraftment in 9 of 14 evaluable patie nts in group 2, the regimen for HLA-mismatched patients was changed in 1984 to include Cy at 60 mg/kg for 2 doses and TBI was added at 1200 cGy to increase immunosuppression (group 3), Sixteen patients in group 3 received marrow grafts after failure to respond to immunosuppressiv e therapy. Eight of the 16 patients in group 3 remain alive without di sease between 1.5 and 11.3 years after transplantation. In conclusion, transplants from phenotypically HLA-identical related donors can be c arried after Cy alone and results are comparable to those observed wit h genotypically HLA-identical siblings, Transplants from related donor s mismatched for one or more HLA loci require a more intensive conditi oning regimen, for example, one containing TBI, to achieve sustained e ngraftment.