Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation: similarity to human PTLD and association with a porcine gammaherpesvirus

Posttransplantation lymphoproliferative disease (PTLD) is a major complicat ion of current clinical transplantation regimens. The lack of a reproducibl e large-animal model of PTLD has limited progress in understanding the path ogenesis of and in developing therapy for this clinically important disease . This study found a high incidence of PTLD in miniature swine undergoing a llogeneic hematopoietic stem cell transplantation and characterized this di sease in swine. Two days before allogeneic peripheral blood stem cell trans plantation, miniature swine were conditioned with thymic irradiation and in vivo T-cell depletion. Animals received cyclosporine daily beginning 1 day before transplantation and continuing for 30 to 60 days. Flow cytometry an d histologic examination were performed to determine the cell type involved in lymphoproliferation. Polymerase chain reaction was developed to detect and determine the level of porcine gammaherpesvirus in involved lymph node tissue. PTLD in swine is morphologically and histologically similar to that observed in human allograft recipients. Nine of 21 animals developed a B-c ell lymphoproliferation involving peripheral blood (9 of 9), tonsils, and l ymph nodes (7 of 9) from 21 to 48 days after transplantation. Six of 9 anim als died of PTLD and 3 of 9 recovered after reduction of immunosuppression. A novel porcine gammaherpesvirus was identified in involved tissues. Minia ture swine provide a genetically defined large-animal model of PTLD with ma ny characteristics similar to human PTLD. The availability of this reproduc ible large-animal model of PTLD may facilitate the development and testing of diagnostic and therapeutic approaches for prevention or treatment of PTL D in the clinical setting. (Blood, 2001;97:1467-1473) (C) 2001 by The Ameri can Society of Hematology.