title: Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi's anemia: a European Group for Immunodeficiency/European Group for Bone Marrow Transplantation report.
abstract: Forty-six infants and children suffering from either inherited immunodeficiency disorders (Wiskott-Aldrich syndrome, functional T-cell immunodeficiency with or without HLA class II expression deficiency), malignant osteopetrosis, or Fanconi's anemia received HLA-nonidentical bone marrow transplantation (BMT) from related donors. Bone marrow was T-cell depleted to reduce the risk of graft-versus-host disease (GVHD). To prevent graft failure, a mouse monoclonal antibody specific for the CD11a-lymphocyte function-associated antigen 1 (LFA-1) molecule was infused into the patients. Eleven patients received five infusions of 0.1 mg/kg every other day from day -3 to +5. Thirty-five patients received 0.2 mg/kg daily from day -3 to +6. The overall sustained engraftment rate was 72% instead of 26.1% in a historical control group of 24 patients similarly treated except for the infusion of the anti-LFA-1 antibody. No late rejection occurred. The T-cell depletion method (E-rosetting or Campath IM plus complement) resulted in different rate of engraftment (83.3% v 57.9%, respectively, P = .05). Engraftment rate was slightly but not significantly influenced by the degree of HLA incompatibility between donor and recipient. Acute GVHD of grade II or more occurred in 35.5% of the patients and the rate of chronic GVHD was 12.9%. The overall actuarial survival rate with a functional graft is 47.3% with a mean follow-up of 28.0 months for patients with immunodeficiency and osteopetrosis, while none of the four patients with Fanconi's anemia survived. The development of full T-cell functions took on the average 6 months and of full B-cell functions 10 months. Significant infectious problems developed in the majority of the patients during the posttransplant course. Epstein-Barr virus-induced B-cell proliferative syndromes were observed in seven patients, six of whom had Wiskott-Aldrich syndrome. Correction of immunodeficiency was comparable in terms of kinetics and quality with that observed in patients with severe combined immunodeficiency undergoing HLA-nonidentical BMT. Correction of osteopetrosis appears not to be different from what has been observed after HLA-identical BMT. The in vivo use of an anti-CD11a-LFA-1 antibody as an additional immunosuppressive therapy in HLA-nonidentical BMT may thus promote engraftment and survival with correction of the primary disease in a significant number of patients with life-threatening immunodeficiency and osteopetrosis, but not with Fanconi's anemia.
authors.affiliation: Department of Pediatrics, Hôpital des Enfants-Malades, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: W
authors.initials: W
authors.lastname: Friedrich
authors.forename: A
authors.initials: A
authors.lastname: Fasth
authors.forename: S
authors.initials: S
authors.lastname: Blanche
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: D
authors.initials: D
authors.lastname: Girault
authors.forename: F
authors.initials: F
authors.lastname: Veber
authors.forename: J
authors.initials: J
authors.lastname: Vossen
authors.forename: M
authors.initials: M
authors.lastname: Lopez
authors.forename: C
authors.initials: C
authors.lastname: Griscelli
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002678:Chimera; D005199:Fanconi Anemia / Q000601:surgery; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000601:surgery; D066298:In Vitro Techniques; D007223:Infant; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D010022:Osteopetrosis / Q000601:surgery; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1