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Blood, 1 March 2001, Vol. 97, No. 5, pp. 1467-1473
TRANSPLANTATION
Posttransplantation lymphoproliferative disease in miniature
swine after allogeneic hematopoietic cell transplantation:
similarity to human PTLD and association with a porcine
gammaherpesvirus
Christene A. Huang,
Yasushi Fuchimoto,
Zachary L. Gleit,
Thomas Ericsson,
Adam Griesemer,
Rachel Scheier-Dolberg,
Elizabeth Melendy,
Hiroshi Kitamura,
Jay A. Fishman,
Judith A. Ferry,
Nancy Lee Harris,
Clive Patience, and
David H. Sachs
From the Transplantation Biology Research Center,
Massachusetts General Hospital/Harvard Medical School, Boston, MA;
Biotransplant, Inc., Charlestown, MA; the Department of Pathology,
Massachusetts General Hospital, Boston, MA; and the Department of
Infectious Diseases, Massachusetts General Hospital, Boston, MA.
Posttransplantation lymphoproliferative disease (PTLD) is a major
complication of current clinical transplantation regimens. The lack of
a reproducible large-animal model of PTLD has limited progress in
understanding the pathogenesis of and in developing therapy for this
clinically important disease. This study found a high incidence of PTLD
in miniature swine undergoing allogeneic hematopoietic stem cell
transplantation and characterized this disease in swine. Two days
before allogeneic peripheral blood stem cell transplantation, 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 and
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-cell lymphoproliferation involving
peripheral blood (9 of 9), tonsils, and lymph nodes (7 of 9) from 21 to
48 days after transplantation. Six of 9 animals died of PTLD and 3 of 9 recovered after reduction of immunosuppression. A novel porcine gammaherpesvirus was identified in involved tissues. Miniature swine
provide a genetically defined large-animal model of PTLD with many
characteristics similar to human PTLD. The availability of this
reproducible large-animal model of PTLD may facilitate the development
and testing of diagnostic and therapeutic approaches for
prevention or treatment of PTLD in the clinical setting.

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