Risk factors for the development of post-transplant lymphoproliferative disorder in a large animal model.
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.
Cho
Patricia S
PS
Transplantation Biology Research Center, Massachusetts Genral Hospital/Harvard Medical School, Boston, MA, USA.
Mueller
Nicolas J
NJ
Cameron
Andrew M
AM
Cina
Robert A
RA
Coburn
Rebecca C
RC
Hettiaratchy
Shehan
S
Melendy
Elizabeth
E
Neville
David M
DM
Patience
Clive
C
Fishman
Jay A
JA
Sachs
David H
DH
Huang
Christene A
CA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D017690:Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D016572:Cyclosporine / Q000494:pharmacology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006239:Haplotypes; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000473:pathology; D008285:Major Histocompatibility Complex; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D013552:Swine; D013556:Swine, Miniature; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000473:pathology; D013997:Time Factors; D014180:Transplantation / Q000009:adverse effects*
D007166:Immunosuppressive Agents; D016572:Cyclosporine