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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.
Blood. 1991 Jan 15; 77(2):249-56.Blood

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+Show Affiliations

Department of Pediatrics, Hôpital des Enfants-Malades, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1985691

Citation

Fischer, A, et al. "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." Blood, vol. 77, no. 2, 1991, pp. 249-56.
Fischer A, Friedrich W, Fasth A, et al. 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. Blood. 1991;77(2):249-56.
Fischer, A., Friedrich, W., Fasth, A., Blanche, S., Le Deist, F., Girault, D., Veber, F., Vossen, J., Lopez, M., & Griscelli, C. (1991). 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. Blood, 77(2), 249-56.
Fischer A, et al. 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. Blood. 1991 Jan 15;77(2):249-56. PubMed PMID: 1985691.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. A1 - Fischer,A, AU - Friedrich,W, AU - Fasth,A, AU - Blanche,S, AU - Le Deist,F, AU - Girault,D, AU - Veber,F, AU - Vossen,J, AU - Lopez,M, AU - Griscelli,C, PY - 1991/1/15/pubmed PY - 1991/1/15/medline PY - 1991/1/15/entrez SP - 249 EP - 56 JF - Blood JO - Blood VL - 77 IS - 2 N2 - 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. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/1985691/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)77787-6 DB - PRIME DP - Unbound Medicine ER -