Successful HLA Nonidentical Bone Marrow Transplantation in Three Patients With the Leukocyte Adhesion Deficiency

• Published in: Blood Vol. 74; no. 1; pp. 512 - 516
• Main Authors: Le Deist, F., Blanche, S., Keable, H., Gaud, C., Pham, H., Descamp-Latscha, B., Wahn, V., Griscelli, C., Fischer, A.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.07.1989; The Americain Society of Hematology
• Subjects: Antibody Formation; Antigens, Differentiation - deficiency; Biological and medical sciences; Bone Marrow - immunology; Bone Marrow Transplantation; Cell Adhesion; Chimera; Hematologic Diseases - therapy; HLA Antigens - analysis; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Integrin alphaXbeta2; Killer Cells, Natural - physiology; Leukocytes - physiology; Lymphocyte Function-Associated Antigen-1; Macrophage-1 Antigen; Medical sciences; Human; Immunopathology; HLA-System; Adherence protein; Leukocyte; Homograft; Bone marrow; Various treatments; Hemopathy; Histocompatibility; Immune deficiency
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V74.1.512.512

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 >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.