In Vivo Alemtuzumab Enables Haploidentical Human Leukocyte Antigen-Mismatched Hematopoietic Stem-Cell Transplantation Without Ex Vivo Graft Manipulation

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Abstract
Background. Alemtuzumab, a humanized monoclonal antibody directed against human CD52, has a strong lympholytic effect. This study evaluates the safety of unmanipulated peripheral blood stem-cell transplantation from two or three loci-mismatched related donors using alemtuzumab in vivo. Methods. A total body irradiation-based regimen was used in young patients, whereas those 50 years or older received fludarabine-based conditioning. Alemtuzumab was added to these regimens by intravenous infusion at 0.2 mg/kg per day for 6 days (days −8 to −3). Results. We treated 12 patients with a median age of 49.5 years. Eight patients demonstrated active disease, and four patients demonstrated acute leukemia in high-risk remission. All achieved neutrophil engraftment a median of 17.5 days after transplantation with complete donor-type chimerism. The cumulative incidence of grades III to IV acute graft-versus-host disease was only 9%. Infection-related deaths were not observed. CD3+/CD4+ and CD3+/CD8+ T cells were strongly suppressed within 2 months after transplantation, but recovered on day 90. Relapse was observed in five of eight patients who underwent transplantation for active disease, whereas none of the three patients who underwent transplantation in first remission had a relapse. Conclusions. We conclude that in vivo alemtuzumab enables haploidentical hematopoietic stem-cell transplantation without ex vivo graft manipulation.