A phase II trial of partially incompatible bone marrow transplantation for high-risk acute lymphoblastic leukaemia in children: prevention of graft rejection with anti-LFA-1 and anti-CD2 antibodies. Société Française de Greffe de Moelle Osseuse.
Bone marrow transplantation (BMT) from matched sibling donors has been useful for the treatment of acute lymphoblastic leukaemia in children with a poor prognosis but is not available to more than two-thirds of patients who do not have a matched allogeneic donor. This study was undertaken to assess one strategy of marrow graft rejection prevention when alternative marrow sources such as HLA-phenoidentical unrelated volunteers and HLA-partially incompatible relatives were used. Results have been compared with two matched groups of children with the same risks factors and disease status who underwent HLA-genoidentical or autologous BMT. The conditioning regimen was the same for the three groups of patients; in the study group anti-LFA-1 and anti-CD2 monoclonal antibodies combined with T-cell depletion of the marrow was added to prevent graft rejection and graft-versus-host disease. Nineteen patients were included and followed for a median of 25 months (14 months to 3 years). Bone marrow engraftment occurred in 83% of the evaluable patients. Post-transplantation infectious diseases were the most frequent causes of death in the study group, occurring in 31% of patients. No fatal infections occurred in the two control groups. Post-transplantation relapse of leukaemia occurred in 26% of study group's patients, in 58% of autologous BMT control group's patients and 5% of HLA-genoidentical allogeneic group's patients. The event-free survival was 83% in the HLA-genoidentical control group, and 30% and 24% in the study group and in the autologous control group, respectively. In conclusion, a high rate of engraftment was achieved by the use of anti-LFA-1 and anti CD2 antibodies. Occurrence of a long-lasting immunodeficiency, however, led to a high incidence of lethal infections and relapses. Combined approaches are therefore to be investigated accelerating immune reconstitution after transplantations of T-depleted HLA partially incompatible marrow.
Cavazzana-Calvo
M
M
INSERM U429, Hôpital Necker-Engants Malades, Paris, France.
Bordigoni
P
P
Michel
G
G
Esperou
H
H
Souillet
G
G
Leblanc
T
T
Stephan
J L
JL
Vannier
J P
JP
Mechinaud
F
F
Reiffers
J
J
Vilmer
E
E
Landman-Parker
J
J
Benkerrou
M
M
Baruchel
A
A
Pico
J
J
Bernaudin
F
F
Bergeron
C
C
Plouvier
E
E
Thomas
C
C
Wijdenes
J
J
Lacour
B
B
Blanche
S
S
Fischer
A
A
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D018801:CD2 Antigens / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000517:prevention & control; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D016169:Lymphocyte Function-Associated Antigen-1