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.
Subject(s)
B-Lymphocytes/immunology , Bone Marrow Transplantation/methods , Epstein-Barr Virus Infections/prevention & control , Lymphoproliferative Disorders/prevention & control , Transplantation Conditioning/methods , Bone Marrow Transplantation/adverse effects , Cell Separation , Child , Child, Preschool , Graft Survival/immunology , Graft vs Host Disease/prevention & control , Histocompatibility Testing , Humans , Infant , Retrospective Studies , Survival Rate , T-Lymphocytes/immunologyABSTRACT
Human articular cartilage cells were transfected with the t.-sensitive polyomavirus large T antigen of SV40. Several immortalized chondrocyte cell lines were obtained. The types of acidic polysaccharides and of collagen synthesized suggest dedifferentiation in the in vitro culture system used afterwards to obtain large numbers of cells.