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Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a)
after HLA nonidentical bone marrow transplantation in children with
immunodeficiencies, osteopetrosis, and Fanconi's anemia: a European Group
for Immunodeficiency/European Group for Bone Marrow Transplantation report
A Fischer, W Friedrich, A Fasth, S Blanche, F Le Deist, D Girault, F Veber, J Vossen, M Lopez and C Griscelli
Department of Pediatrics, Hopital des Enfants-Malades, Paris, France.
Forty-six infants and children suffering from either inherited
immunodeficiency disorders (Wiskott-Aldrich syndrome, functional T-cell
immunodeficiency with or without HLA class II expression deficiency),
malignant osteopetrosis, or Fanconi's anemia received HLA-nonidentical bone
marrow transplantation (BMT) from related donors. Bone marrow was T-cell
depleted to reduce the risk of graft-versus-host disease (GVHD). To prevent
graft failure, a mouse monoclonal antibody specific for the
CD11a-lymphocyte function-associated antigen 1 (LFA-1) molecule was infused
into the patients. Eleven patients received five infusions of 0.1 mg/kg
every other day from day -3 to +5. Thirty-five patients received 0.2 mg/kg
daily from day -3 to +6. The overall sustained engraftment rate was 72%
instead of 26.1% in a historical control group of 24 patients similarly
treated except for the infusion of the anti- LFA-1 antibody. No late
rejection occurred. The T-cell depletion method (E-rosetting or Campath IM
plus complement) resulted in different rate of engraftment (83.3% v 57.9%,
respectively, P = .05). Engraftment rate was slightly but not significantly
influenced by the degree of HLA incompatibility between donor and
recipient. Acute GVHD of grade II or more occurred in 35.5% of the patients
and the rate of chronic GVHD was 12.9%. The overall actuarial survival rate
with a functional graft is 47.3% with a mean follow-up of 28.0 months for
patients with immunodeficiency and osteopetrosis, while none of the four
patients with Fanconi's anemia survived. The development of full T-cell
functions took on the average 6 months and of full B-cell functions 10
months. Significant infectious problems developed in the majority of the
patients during the posttransplant course. Epstein-Barr virus- induced
B-cell proliferative syndromes were observed in seven patients, six of whom
had Wiskott-Aldrich syndrome. Correction of immunodeficiency was comparable
in terms of kinetics and quality with that observed in patients with severe
combined immunodeficiency undergoing HLA-nonidentical BMT. Correction of
osteopetrosis appears not to be different from what has been observed after
HLA-identical BMT. The in vivo use of an anti-CD11a-LFA-1 antibody as an
additional immunosuppressive therapy in HLA-nonidentical BMT may thus
promote engraftment and survival with correction of the primary disease in
a significant number of patients with life-threatening immunodeficiency and
osteopetrosis, but not with Fanconi's anemia.
Volume 77,
Issue 2,
pp. 249-256,
01/15/1991
Copyright © 1991 by The American Society of Hematology
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