title: Combined in vitro and in vivo T lymphocyte depletion for the control of graft-versus-host disease following haploidentical marrow transplant.
abstract: Most patients requiring allogeneic bone marrow transplantation (BMT) lack a human leukocyte antigen genotypically identical sibling and require an alternative donor. This carries an increased risk of graft failure 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, related donor. This study of 40 patients used a novel approach combining in vitro and in vivo T cell depletion with T lymphocyte targeted monoclonal antibodies (mAb) and intensified conditioning therapy, including fractionated total body irradiation before etoposide, cytoside arabinoside, cyclophosphamide, and methylprednisolone. Grafts were treated with T10B9.1A-31 mAb, directed against the alpha-beta heterodimer of the T cell receptor, and rabbit complement. In vivo depletion was attempted with an anti-CD5 mAb-Ricin A-chain (H65-RTA) immunotoxin (IT). Study patients were compared with a historical control group of 17 patients not given H65-RTA. Rates of engraftment were not significantly different (93% vs. 100%, P=0.12), although patients receiving IT engrafted more rapidly. The incidence of > grade I GVHD was significantly lower in the study group (36% vs. 100%, P=0.0001), as well as for severe grade III-IV 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 from haploidentical family members is indicated for patients without a matched sibling in whom allogeneic BMT offers the best opportunity to achieve cure.
authors.affiliation: Department of Medicine, University of South Carolina and Richland Memorial Hospital, Columbia, South Carolina 29203 USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Henslee-Downey
authors.forename: R S
authors.initials: RS
authors.lastname: Parrish
authors.forename: J S
authors.initials: JS
authors.lastname: MacDonald
authors.forename: E H
authors.initials: EH
authors.lastname: Romond
authors.forename: E
authors.initials: E
authors.lastname: Marciniak
authors.forename: C
authors.initials: C
authors.lastname: Coffey
authors.forename: G
authors.initials: G
authors.lastname: Ciocci
authors.forename: J S
authors.initials: JS
authors.lastname: Thompson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D012276:Ricin / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; C068230:zolimomab aritox; D012276:Ricin