Allogeneic transplantation across major HLA barriers

Only one-fourth of patients with fatal haematological disorders and malignancies will have an HLA-matched sibling donor to create access to potentially curative allogeneic stem cell transplantation. Advances in medical management, preparation of the graft and prevention of transplant-related complications, particularly rejection and GVHD, now make it possible to use alternative donors who are not genetically HLA-histocompatible with the patient. Some patients identify unrelated donor options using adult volunteers or cord blood units. All patients have immediate access to one or more genetically half-matched (haplo-identical), HLA partially-mismatched related donors. Using safer non-cytotoxic therapies to ablate the patient's immune system, graft preparation to decrease T-lymphocyte and/or increase CD 34+ cell doses, and post-transplant GVHD and infection prophylaxis, rates >95% for engraftment and <25% for grade II-IV GVHD can be achieved. Thus, disease-free survival rates are comparable to other alternative donors with all outcomes adversely influenced by advanced disease status, poor medical performance and older age.