Abstract
Immunosuppression for solid organ transplantation increases lymphoproliferative disease risk. While central nervous system (CNS) involvement is more rare, we noticed an increase in primary CNS (PCNS) disease. To investigate a potential association with the immunosuppressive regimen we identified all post-transplant lymphoproliferative disease (PTLD) cases diagnosed over a 28-year period at our institution (174 total, 29 PCNS) and all similar cases recorded in a United Network for Organ Sharing-Organ Procurement and Transplant Network (UNOS-OPTN) datafile. While no PCNS cases were diagnosed at our institution between 1986 and 1997, they comprised 37% of PTLD cases diagnosed from 2011-2014. PCNS disease was more often associated with renal vs. other organ transplant, Epstein-Barr virus, large B-cell morphology and mycophenolate mofetil (MMF) as compared to PTLD that did not involve the CNS. Calcineurin inhibitors were protective against PCNS disease when given alone or in combination with MMF. A multivariate analysis of a larger UNOS-OPTN dataset confirmed these findings, where both MMF and lack of calcineurin inhibitor usage were independently associated with risk for development of PCNS PTLD. These findings have significant implications for the transplant community, particularly given the introduction of new regimens lacking calcineurin inhibitors. Further investigation into these associations is warranted.
Highlights
Post-transplant lymphoproliferative disease (PTLD) is a well-known complication of solid organ transplantation with both type and level of immunosuppression associated with risk for developing lymphoproliferative disease
Additional evidence emerged in a larger French study, where Snanoudj et al characterized post-transplant lymphoproliferative disease (PTLD) arising in patients who received kidney transplants between 1976 and 1998 and found that 6 of 10 patients diagnosed with primary CNS (PCNS) PTLD > 3 years post-transplant had been recently switched from azathioprine to mycophenolate mofetil (MMF) [14]
A multi-center study of 84 PCNS PTLD patients by Evens et al found that MMF was the most common immunosuppressant prior to diagnosis (69 of 84 patients), and 21 of them were on MMF as a monotherapy [15]
Summary
Post-transplant lymphoproliferative disease (PTLD) is a well-known complication of solid organ transplantation with both type and level of immunosuppression associated with risk for developing lymphoproliferative disease. Renal transplant recipients have been reported to have a relative risk of 12.6 of developing PTLD compared to the general population of developing lymphoma, while transplants requiring a higher level of immunosuppression, such as liver or combined heart/lung, have a relative risk from 30 to as high as 240 [1]. Drug mechanism may play a role as anti-IL-2 receptor antibodies, when used in www.impactjournals.com/oncotarget equivalent clinical situations as OKT3 and ATG, were as effective in reducing graft loss [3] but were not associated with increased PTLD risk [1, 3]. PTLDs arose in the graft itself, the gastrointestinal tract or presented as disseminated disease [1, 8]
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