Posttransplant lymphoproliferative disorder associated with primate gamma-herpesvirus in cynomolgus monkeys used in pig-to-primate renal xenotransplantation and primate renal allotransplantation.

Background: A series of immunosuppressed cynomolgus monkeys were used in porcine-to-primate and primate-to-primate renal transplantation. In a number of animals nodal and extranodal lymphomas as well as areas of lymphoid hyperplasia in multiple organs (posttransplant lymphoproliferative disorder, PTLD) were recorded.

Methods: PTLD was characterized with respect to manifestation sites, histopathology, immunophenotype, and association with primate Epstein Barr-like Virus by in situ hybridization and quantitative polymerase chain reaction.

Results: PTLD was observed in 10 of 245 xenotransplanted and 9 of 231 allotransplanted monkeys; its detection in xenotransplanted animals was significantly earlier after transplantation than that in allo-transplanted animals (median, 40 and 104 days, respectively; P<0.001). In the xenotransplanted animals, four cases showed a B-cell lymphoma and six cases were nonneoplastic (lymphoid hyperplasia). All nine PTLD cases from allotransplanted animals were diagnosed as lymphoma. There was no clear relationship between the use of a particular drug or drug combination in maintenance immunosuppression and the occurrence of PTLD. Fourteen of 19 animals (six of the cases from xenotransplants, eight from the allotransplant series) were positive by in situ hybridization with oligonucleotide probes detecting primate gamma-herpesvirus.

Conclusion: These data indicate that PTLD in the xeno- and allotransplanted cynomolgus monkeys are associated with primate gamma-herpesvirus-induced B-cell proliferation.