COMBINED IN-VITRO AND IN-VIVO T-LYMPHOCYTE DEPLETION FOR THE CONTROL OF GRAFT-VERSUS-HOST DISEASE FOLLOWING HAPLOIDENTICAL MARROW TRANSPLANT

Most patients requiring allogeneic bone marrow transplantation (BMT) l ack a human leukocyte antigen genotypically identical sibling and requ ire an alternative donor, This carries an increased risk of graft fail ure and acute graft-versus-host disease (GVHD), We sought to overcome these problems with transplants by using grafts obtained from the most readily available source: the haploidentical, partially mismatched, r elated donor, This study of 40 patients used a novel approach combinin g in vitro and in vivo T cell depletion with T lymphocyte targeted mon oclonal antibodies (mAb) and intensified conditioning therapy, includi ng fractionated total body irradiation before etoposide, cytoside arab inoside, cyclophosphamide, and methylprednisolone, Grafts were treated with T10B9 . 1A-31 mAb, directed against the alpha beta heterodimer o f the T cell receptor, and rabbit complement, In vivo depletion was at tempted with an anti-CD5 mAb-Ricin A-chain (H65-RTA) immunotoxin (IT), Study patients were compared with a historical control group of 17 pa tients not given H65-RTA, Rates of engraftment were not significantly different (93% vs, 100%, P=0.12), although patients receiving IT engra fted more rapidly, The incidence of > grade I GVHD was significantly l ower in the study group (36% vs, 100%, P=0.0001), as well as for sever e grade III-TV GVHD (19% vs, 92%, P=0.0001), Five-year survival tended to be improved in the study group (40% vs, 18%, P=0.21). Transplant f rom haploidentical family members is indicated for patients without a matched sibling in whom allogeneic BMT offers the best opportunity to achieve cure.