title: Successful HLA nonidentical bone marrow transplantation in three patients with the leukocyte adhesion deficiency.
abstract: Three consecutive patients with the severe phenotype of leukocyte adhesion deficiency characterized by a defective expression of LFA-1, Mac-1 (CR3), and p150.95 on leukocytes have received HLA partially incompatible bone marrow transplantation (BMT). The degree of HLA incompatibility between related donors and recipients was 2 HLA antigens in one and one full haplotype in the two others. Graft-v-host disease (GVHD) prophylaxis consisted in T-cell depletion of the bone marrow inoculum and a 60-day course of cyclosporin A. A first attempt led to autologous recovery in one patient. The second transplant in this patient and the first transplant in the two others led to stable partial engraftment of lymphocytes and phagocytic cells, as shown by expression of adhesion molecules (LFA-1, Mac-1) on leukocytes and by HLA typing and restriction fragment-length polymorphism studies using minisatellite probes. Although the level of mixed chimerism was lower in one patient (7% to 30% donor cells) and greater than 50% in the two others, recovery of lymphocyte and phagocytic cell functions was sufficient enough to allow the patient to lead a normal life, infection free in the three cases. These patients, now 57, 32, and 19 months post-transplant, are in good condition without any therapy. These results lead us to propose that the LFA-1 molecule plays a role in HLA-incompatible graft rejection, probably by mediating adhesion of cytotoxic T and non-T lymphocytes to their targets.
authors.affiliation: INSERM U 132, Hopital Necker, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: S
authors.initials: S
authors.lastname: Blanche
authors.forename: H
authors.initials: H
authors.lastname: Keable
authors.forename: C
authors.initials: C
authors.lastname: Gaud
authors.forename: H
authors.initials: H
authors.lastname: Pham
authors.forename: B
authors.initials: B
authors.lastname: Descamp-Latscha
authors.forename: V
authors.initials: V
authors.lastname: Wahn
authors.forename: C
authors.initials: C
authors.lastname: Griscelli
authors.forename: A
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000917:Antibody Formation; D000943:Antigens, Differentiation / Q000172:deficiency; D001853:Bone Marrow / Q000276:immunology; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion; D002678:Chimera; D006680:HLA Antigens / Q000032:analysis; D006402:Hematologic Diseases / Q000628:therapy*; D006801:Humans; D016167:Integrin alphaXbeta2; D007694:Killer Cells, Natural / Q000502:physiology; D007962:Leukocytes / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen
chemical_list: D000943:Antigens, Differentiation; D006680:HLA Antigens; D016167:Integrin alphaXbeta2; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen