RARE-02. PRIMARY CNS POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE (PCNS-PTLD): RECOGNIZING THE ENTITY, MINIMIZING TREATMENT TOXICITY, AND DEVELOPMENT OF SURVEILLANCE TOOLS IN RENAL TRANSPLANT PATIENTS

PCNS-PTLD is a rare complication of solid organ transplantation (SOT) and is a distinct entity from primary CNS lymphoma (PCNSL). With fewer than 90 cases reported since 1970, there are no treatment standards. Existing data supports combining reduction of immunosuppression (RI), whole-brain radiotherapy, monoclonal antibody therapy, and systemic/IT chemotherapy. Treating kidney SOT PTLD is complicated by reduced renal clearance, contrast-dye restrictions, and nephrotoxicity. Treatment complications and allograft rejection cause early morbidity and mortality. Rapid identification of serum/CSF supporting diagnostic markers such as active EBV replication, elevated CSF protein, and positive cytology/flow cytometry is critical. We report three cases of B/T-cell PTLD in renal-SOT patients 1–27 years on immunosuppression (steroids, mycophenolate, tacrolimus/sirolimus) who presented with focal neurologic deficits and multifocal MRI lesions. After confirming CNS-isolated disease patients were treated with partial-RI, dexamethasone, and induction with rituximab weekly cycles. Patients had objective responses and underwent consolidative rituximab therapy q21-days with restaging. Residual enhancing lesions were treated by stereotactic radiosurgery and one year of temozolomide chemotherapy days 1–5 on a 28-day cycle. We monitored serum LD, drug levels, and serum EBV as indicators for progression/recurrence. Patients achieved complete responses and mOS has not been met. Long-term survival in PCNS-PTLD is one distinguishing feature from PCNSL. With multiple treatment obstacles in renal-SOT PT early recognition and minimally toxic regimens improve patient outcomes. This data challenges traditional paradigms in diagnosis and treatment of PTLD, specifically EBV+ disease occurring >6 years post SOT. We propose that the specialized CNS immune microenvironment permits EBV driving of neoplastic progression, which is exquisitely sensitive to B-cell targeting concurrent with partial restoration of host immunity. Furthermore, targeted radiotherapy, temozolomide, and partial immunosuppression maintains patient quality-of-life and reduce risk for allograft rejection.