title: Prevention of EBV-induced B-lymphoproliferative disorder by ex vivo marrow B-cell depletion in HLA-phenoidentical or non-identical T-depleted bone marrow transplantation.
abstract: HLA-mismatched bone marrow transplantation (BMT) is hampered by three major complications: graft rejection, acute graft-versus-host disease (aGVHD) and delayed immune reconstitution. Infusion of anti-LFA1 plus anti-CD2 monoclonal antibodies (MAb), combined with ex-vivo T-cell depletion of the graft, was efficient in preventing graft rejection and aGVHD. Nevertheless, disease-free survival was limited by the high frequency of lethal infections, including EBV-induced lymphoproliferative disease (BLPD), which originates mostly from donor B cells, with an incidence of 5-30%. To decrease the rate of this complication, ex-vivo B-cell depletion was attempted. This study compares a group of 19 patients who received a T- and B-cell-depleted marrow from an HLA-mismatched related donor with a retrospective control group of 19 patients, who had received T-cell-depleted marrow by the same method. The level of T-cell depletion was similar in the two groups. For B-cell depletion, two different methods were compared. The median number of B cells infused in the study group was 0.46/kg. Engraftment and aGVHD incidence were similar in the two groups. No EBV donor-derived BPLD occurred in the study group, compared with seven in the control group, four of whom died because of EBV-BPLD. Event-free survival was significantly different between the two groups. We conclude that ex-vivo B-cell depletion of the graft may be a useful means of preventing EBV-BPLD, and warrants further study on a larger group of patients.
authors.affiliation: Etablissement de Transfusion Sanguine-Hôpital Necker, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: D
authors.initials: D
authors.lastname: Bensoussan
authors.forename: N
authors.initials: N
authors.lastname: Jabado
authors.forename: E
authors.initials: E
authors.lastname: Haddad
authors.forename: E
authors.initials: E
authors.lastname: Yvon
authors.forename: M
authors.initials: M
authors.lastname: Moskwa
authors.forename: A
authors.initials: A
authors.lastname: Tachet des Combes
authors.forename: M
authors.initials: M
authors.lastname: Buisson
authors.forename: P
authors.initials: P
authors.lastname: Morand
authors.forename: J M
authors.initials: JM
authors.lastname: Virion
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: A
authors.initials: A
authors.lastname: Fischer
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000517:prevention & control; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000517:prevention & control*; D012189:Retrospective Studies; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*