title: In vivo infusion of anti-LFA-1 and anti-CD2 antibodies prevents graft failure after HLA partially incompatible bone marrow transplantation in children with high risk acute lymphoblastic leukaemia.
abstract: Bone marrow transplantation (BMT) from matched sibling donors is the therapy of choice for children with high-risk acute lymphoblastic leukaemia in children. It is however not available to more than two-thirds of patients who lack a matched donor. Here, we review the outcome of 28 patients with high-risk ALL who were transplanted in France with alternative marrow sources such as HLA-phenoidentical unrelated volunteers and HLA-partially incompatible relatives. For these patients, we tested the possibility to prevent T-depleted marrow graft rejection by infusing in vivo two monoclonal antibodies directed against adhesion receptors i.e., LFA-1 and CD2. Two previous multicenter trials in children transplanted with partially incompatible bone marrow for inborn errors of metabolism showed their efficacy in this setting. Twenty eight patients were enrolled in this study and followed for a median of 4.4 years. Bone marrow engraftment occurred in 81% of the evaluable patients. Post-transplantation leukaemic relapse was the most frequent cause of death in this group of patients, and occurred in 39% of patients. The second most frequent complication was infectious disease, while an EBV-induced B-lymphocyte proliferative disorder occurred in four patients. In conclusion, T-cell-depletion combined with infusion of anti-LFA-1 and anti-CD2 antibodies is efficient in preventing graft failure and GVHD in this group of children with high-risk leukaemia undergoing partially incompatible BMT. The overall DFS is not improved in contrast to what has been previously observed in patients with immunodeficiencies transplanted with a similar rejection prophylaxis. Other approaches are therefore needed aiming either at preserving donor T-cell mediated immunity or accelerating immune reconstitution.
authors.affiliation: Etablissement de transfusion sanguine, Unité d'Immunologie et d'Hématologie and INSERM U429, Hôpital Necker Enfants Malades, PARIS, France.
authors.forename: M
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: N
authors.initials: N
authors.lastname: Jabado
authors.forename: P
authors.initials: P
authors.lastname: Bordigoni
authors.forename: G
authors.initials: G
authors.lastname: Michel
authors.forename: E
authors.initials: E
authors.lastname: Haddad
authors.forename: F
authors.initials: F
authors.lastname: Mechinaud
authors.forename: J
authors.initials: J
authors.lastname: Landman-Parker
authors.forename: T
authors.initials: T
authors.lastname: Leblanc
authors.forename: E
authors.initials: E
authors.lastname: Plouvier
authors.forename: A
authors.initials: A
authors.lastname: Baruchel
authors.forename: J L
authors.initials: JL
authors.lastname: Stephan
authors.forename: G
authors.initials: G
authors.lastname: Souillet
authors.forename: E
authors.initials: E
authors.lastname: Vilmer
authors.forename: J
authors.initials: J
authors.lastname: Wijdenes
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: A
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D016026:Bone Marrow Transplantation; D018801:CD2 Antigens / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy*; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D006680:HLA Antigens; D016169:Lymphocyte Function-Associated Antigen-1