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.
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.
Cavazzana-Calvo
M
M
Etablissement de Transfusion Sanguine-Hôpital Necker, Paris, France.
Bensoussan
D
D
Jabado
N
N
Haddad
E
E
Yvon
E
E
Moskwa
M
M
Tachet des Combes
A
A
Buisson
M
M
Morand
P
P
Virion
J M
JM
Le Deist
F
F
Fischer
A
A
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*