Risk factors for the development of post-transplant lymphoproliferative disorder in a large animal model

Patricia S. Cho, Nicolas J. Mueller, Andrew M. Cameron, Robert A. Cina, Rebecca C. Coburn, Shehan Hettiaratchy, Elizabeth Melendy, David M. Neville, Clive Patience, Jay A. Fishman, David H. Sachs, Christene A. Huang

Research output: Contribution to journalArticlepeer-review

Abstract

A high incidence of a post-transplant lymphoproliferative disorder (PTLD) is observed in miniature swine conditioned for allogeneic hematopoietic cell-transplantation using a protocol involving T-cell depletion and cyclosporine therapy. This study was designed to assess contributing factors to disease development. Forty-six animals were studied including 12 (26%) that developed PTLD. A number of risk factors for PTLD were examined, including degree of immunosuppression, degree of MHC mismatch and infection by a porcine lymphotrophic herpesvirus (PLHV-1). Flow cytometry was used to measure host and donor T- and B-cell levels in the peripheral blood. Porcine lymphotrophic herpesvirus viral load was determined by quantitative PCR. Animals developing PTLD had significantly lower levels of T cells on the day of transplant. Cyclosporine levels did not differ significantly between animals with and without PTLD. Animals receiving transplants across a two-haplotype mismatch barrier showed an increased incidence of PTLD. All animals with PTLD had significant increases in PLHV-1 viral loads. Porcine lymphotrophic herpesvirus viral copy numbers remained at low levels in the absence of disease. The availability of a preclinical large-animal model with similarities to PTLD of humans may allow studies of the pathogenesis and treatment of that disorder.

Original languageEnglish (US)
Pages (from-to)1274-1282
Number of pages9
JournalAmerican Journal of Transplantation
Volume4
Issue number8
DOIs
StatePublished - Aug 2004
Externally publishedYes

Keywords

  • Hematopoietic cell transplantation
  • Immunosuppression
  • Miniature swine
  • Porcine lymphotrophic herpes virus
  • Post transplant lymphoproliferative disease

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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