Reduction of Immunosuppression Does Not Significantly Impact Incidence of Renal Transplant Graft Rejection Following a Diagnosis of Post-Transplant Lymphoproliferative Disorder

INTRODUCTION

Post-transplant lymphoproliferative disorder (PTLD) is a rare and potentially fatal complication of both solid organ and hematopoietic stem cell transplant. Incidence of PTLD varies based on extent of immunosuppression (IS). The long-term impact of IS reduction on graft function following a diagnosis of PTLD in renal transplant recipients is unclear.

METHODS

Data was collected via review of electronic medical records (EMR) for 1628 patients who underwent renal transplant at our institution from September 1, 1996- June 30, 2015. Twenty-seven patients (1.7%) developed PTLD defined as an early lesion, polymorphic PTLD, or monomorphic PTLD. 10 patients did not have clinical data available in the EMR and were excluded. Graft rejection and failure rates of 17 patients prior to diagnosis of PTLD were compared to the same group at most recent follow up using a two-sided binomial test.

RESULTS

Median age at PTLD diagnosis was 50 years (range 24-79 years). Kidney donor type included living related (8), deceased donor (6), and deceased donor followed by a living related donor (1). We were unable to identify donor type for 2 patients.

At time of PTLD diagnosis, 16 patients were on tacrolimus-based IS regimens combined with either mycophenolic acid (6), prednisone (1), mycophenolic acid with prednisone (7), or azathioprine (2). 1 patient was on a sirolimus-based regimen with mycophenolic acid. Four of 17 patients experienced an episode of acute (1) or chronic (3) renal graft rejection prior to PTLD diagnosis. Two of 3 patients with chronic rejection developed graft failure. Median time patients were on IS prior to a diagnosis of PTLD was 11 years (range 1-37 years).

PTLD histology included polymorphic PTLD (2) and monomorphic PTLD (14), 1 of which was a T-cell lymphoma. There was 1 early lesion thought secondary to Epstein Barr virus (EBV) viremia. Immunohistochemical staining for EBV was positive in 2 out of 14 available cases. There were no cases of classical Hodgkin lymphoma. Treatment included reduction of immunosuppression in all patients combined with either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in 8 patients, single agent rituximab followed by R-CHOP (3), dose adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (daR-EPOCH) in 3 patients, bexarotene plus phototherapy (1), whole brain radiation (1), and reduction of IS only (1). Thirteen of 17 patients achieved complete remission (CR) following their initial treatment regimen. Median disease free survival or relapse free survival was 55 months (range 9-98 months). There were no cases with partial response or stable disease. Two patients developed relapsed disease. One relapsed 6 months after remission, the other 7 months. At time of analysis, 11 patients were alive, 2 died of refractory PTLD, 2 died of pneumonia while in CR, and 2 were lost to follow up.

IS regimens were held in all patients following a diagnosis of PTLD and subsequently resumed at an attenuated level if patient achieved CR. Three of 17 patients had an episode of renal graft rejection following reduction of IS after PTLD diagnosis, including acute T-cell-mediated (2) and chronic rejection (1). The patient with chronic rejection developed graft failure following IS reduction.

CONCLUSION

At median follow up of 24 months, there was no significant difference in the overall rate of renal graft rejection following PTLD development as compared to prior to diagnosis of PTLD (p= 0.78). There was no significant difference in rate of acute rejection after diagnosis of PTLD compared to prior to diagnosis (p= 0.26). Additionally, there was no significant difference in the rate of renal graft failure following PTLD development compared to prior to diagnosis (p= 0.71). Our rate of PTLD development in renal transplant recipients was comparable to previously reported data.