In vivo infusion of anti LFA-1 antibody in HLA non-identical bone marrow transplantation in children: serum concentrations and biological effects.
The mouse monoclonal antibody 25-3 specific for the alpha subunit of LFA-1 (CD11a) has been infused to children undergoing HLA non-identical bone marrow transplantation because of lethal inherited diseases or of leukemia in order to prevent graft failure. We have assessed the serum concentrations of the antibody infused according to two regimens: 0.1 mg/kg five times, every alternate day (eight patients) or 0.2 mg/kg daily for 10 days (30 patients). Serum trough levels of 25-3 antibody in the first group were constantly found to be low (less than 0.6 micrograms/ml) while 25-3 serum concentration in the second group rose progressively to a mean value of 2.2 micrograms/ml. Serum antibody concentrations were significantly lower in patients with greater antigenic mass, i.e. with splenomegaly, or non conditioned. The engraftment rate was slightly higher in patients treated by the daily infusion of 25-3 for 10 days. No immunization against 25-3 antibody occurred. One patient who subsequently received other mouse anti-B cell antibodies eventually produced anti-isotype antibodies. The consequences of 25-3 infusion on leukocyte counts has been evaluated in the group of patients (n = 6) with severe combined immunodeficiency who did not receive any chemotherapy and in one who was treated with 25-3 because of acute graft-versus-host disease. In none of the cases did 25-3 antibody infusion modify blood leukocyte counts. In addition, it was shown that saturation of LFA-1 on leukocytes was a transient phenomenon, since it could not be found 24 h following infusion of 25-3 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
Perez
N
N
Inserm U 132, Hôpital Necker-Enfants Malades, Paris, France.
Le Deist
F
F
Chatenoud
L
L
Chanteloup
N
N
Griscelli
C
C
Fischer
A
A
D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D000943:Antigens, Differentiation / Q000276:immunology* / Q000494:pharmacology; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000187:drug effects; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D006680:HLA Antigens; D016169:Lymphocyte Function-Associated Antigen-1