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.