Failure of a CD18/anti-LFA1 monoclonal antibody infusion to prevent graft rejection in leukemic patients receiving T-depleted allogeneic bone marrow transplantation.
CD18 antibodies react with the common beta chain of the human leukocyte function antigen (LFA1)* and thus block the functions mediated by the three identified molecules in humans. A murine CD18 monoclonal antibody was infused in 8 leukemic patients receiving allogeneic T-depleted bone marrow transplantation in order to prevent graft rejection. This was part of the conditioning, including total-body irradiation and high-dose chemotherapy, given to all patients. To prevent graft-versus-host disease the donor bone marrow T cells were depleted using complement-mediated cytolysis or a ricin A conjugate immunotoxin, and cyclosporine or methotrexate were given posttransplant. A persistent level of free circulating anti-LFA1 antibody was detected in 5/8 patients. Despite this, 5 graft failures occurred, with 2 patients experiencing late rejection (days 60 and 97) following HLA-identical transplantation and 3 patients having no engraftment following haplo-mismatched transplant. One other patient died of early sepsis. Only 2 patients (who differed at 1 HLA locus from their donor) are alive with long-term complete chimerism (300 and 315 days). Transient inhibition of recipients' leukocyte functions with an anti-LFA1 antibody did not appear to facilitate engraftment of allogeneic T-depleted marrow transplantation for leukemias.
Baume
D
D
Service d'Hématologie Clinique, Institut Gustave Roussy, Villejuif, France.
Kuentz
M
M
Pico
J L
JL
Beaujean
F
F
Cordonnier
C
C
Vernant
J P
JP
Hayat
M
M
Bernard
A
A
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000943:Antigens, Differentiation / Q000276:immunology*; D016026:Bone Marrow Transplantation; D018821:CD18 Antigens; D002648:Child; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007262:Infusions, Intravenous; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy*; D016169:Lymphocyte Function-Associated Antigen-1; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins