The role of total body irradiation in the conditioning of patients receiving haploidentical stem cell transplantation.

BACKGROUND: Nearly 40% of patients requiring a hematopoietic stem cell transplant lack a suitable donor. However, virtually all these patients have a potential family donor with whom they share one HLA haplotype. METHODS: We report the rationale for making hematopoietic stem cell transplantation from haploidentical related donors feasible, as well as the method followed to achieve this. Two studies are reported, designed to overcome the problem of rejection and graft-versus-host disease after haploidentical stem cell transplantation. We describe how our total body irradiation-based, highly immuno- and myelosuppressive conditioning regimens were developed and how they have been modified over the years in an attempt to improve the clinical outcome of high-risk acute leukemia patients receiving large numbers of extensively T-cell-depleted hematopoietic stem cell transplantations from full-haplotype mismatched family donors. RESULTS: A high engraftment rate and an extremely low incidence of graft-versus-host disease were obtained. Modifications of the pretransplant schedules allowed the reduction of transplant-related toxicity. CONCLUSIONS: The main obstacles that limited the use of haploidentical stem cell transplantation have been overcome. The procedure is now a reality that should be recommended in high-risk acute leukemia patients who do not have a suitable matched donor