Transplantation of hematopoietic stem cells from unrelated volunteer donors.

Transplantation of hematopoietic stem cells from human leukocyte antigen (HLA)-compatible unrelated volunteer donors have become feasible for more than 70% of patients without a family match. Chronic myeloid leukemia is the most common indication for unrelated donor marrow transplantation. The 5year survival for patients up the age of 50 years has improved to 75% with transplantation in the chronic phase within the first year from after diagnosis, the selection of a closely matched donor, and the prophylactic use of fluconazole and ganciclovir. However, graft failure, and acute and chronic graft-versus-host disease (GVHD) remain frequent causes of morbidity and death. The incidence of graft failure is correlated with multiple Class I HLA-A, B, and C mismatching in the donor. The risk of grades III-IV acute GVHD is highest with Class II HLADRB1 and DQB1 mismatching in the recipient. Refractoriness to glucocorticoid therapy is the dominant factor predisposing to chronic GVHD. Mismatching for a single Class I or Class II allele has no effect on survival, but mortality is increased by simultaneous mismatching for Class I and Class II alleles. Transplantation of marrow from an HLA-matched, unrelated donor is safe and effective therapy for selected patients with hematological malignancy. Since fully matched donors will not available for many patients, the challenge is developing methods for marrow transplantation that can decrease morbidity and improve survival despite genetic disparity between donor and recipient.