Prevention of graft failure by an anti-HLFA-1 monoclonal antibody in HLA-mismatched bone-marrow transplantation

Abstract

Seven patients with immunodeficiencies (Wiskott-Aldrich syndrome, combined immunodeficiency, and osteopetrosis) were given a mouse monoclonal antibody against the alpha subunit of human leucocyte functional antigen (HLFA-1; CD18) to facilitate the engraftment of mismatched haploidentical related-donor bone marrow. Other conditioning included busulphan, cyclophosphamide, and antilymphocyte globulin. To prevent graft-versus-host disease the bone-marrow T cells were depleted with sheep erythrocyte rosetting and cyclosporin therapy was given. HLFA-1 antibody injections were well tolerated without side-effects except slight, transient fever (38-40 degrees) after the first injection. Engraftment was rapid in all seven patients. The regenerating leucocytes were of donor origin in all cases, and two patients have a mixed chimera. Two patients died from infections. The others are alive and well 60-395 days after transplantation. In a historical control group given the same treatment without anti-HLFA-1 infusion, only one of seven transplants partially engrafted; only two patients remain alive with autologous reconstitution but with uncorrected immunodeficiency.