Failure of a CD18/anti-LFA1 monoclonal antibody infusion to prevent graft rejection in leukemic patients receiving T-depleted allogeneic bone marrow transplantation

Transplantation. 1989 Mar;47(3):472-4. doi: 10.1097/00007890-198903000-00014.

Abstract

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.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / administration & dosage*
  • Antigens, Differentiation / immunology*
  • Bone Marrow Transplantation*
  • CD18 Antigens
  • Child
  • Female
  • Graft Rejection
  • Humans
  • Infusions, Intravenous
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Lymphocyte Function-Associated Antigen-1
  • Male
  • Membrane Glycoproteins / immunology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation
  • CD18 Antigens
  • Lymphocyte Function-Associated Antigen-1
  • Membrane Glycoproteins