Treatment of aplastic anemia with marrow grafts from related donors other than HLA genotypically‐matched siblings

Abstract

24 patients with severe aplastic anemia were given marrow grafts from related donors other than HLA‐identical siblings. 2 patients received cyclophosphamide (CY) plus total body irradiation (TBI) as part of their preparative regimen. The remaining 22 received CY only, with or without other immunosuppressive agents. All donor/recipient pairs were genotypically identical for one HLA haplotype and had variable numbers of similar antigens on the unshared haplotypes. 6 patients received marrow from donors who were HLA‐A, B, DR, Dw phenotypically matched. All 6 are currently engrafted and surviving, 3 after having had Acute Graft‐Versus‐Host Disease (AGVHD) and 4 with Chronic Graft‐Versus‐Host‐Disease (CGVHD). The remaining 18 patients received HLA partially‐incompatible grafts. Of 17 partially‐matched patients evaluable for engraftment, 10 had failure of engraftment or graft rejection; all died of infectious complications. Of the 7 mismatched patients achieving sustained engraftment, all developed grade II–IV AGVHD. 6 of 11 patients who survived more than 100 d after transplant had CGVHD. Currently, 2 of 18 patients who were mismatched for 1 or more loci survive with hematological recovery. This study shows that patients with refractory severe aplastic anemia who have a phenotypically‐matched donor clearly benefit from a marrow transplant using only CY for conditioning. Those with partially‐matched donors are at high risk for graft rejection and may need additional immunosuppression such as CY plus TBI to facilitate engraftment. For those who engraft, more effective prophylactic and/or treatment measures for AGVHD are needed to improve survival.