RARE-12. MINIMIZING FALLOUT WHILE MAXIMIZING EFFICACY IN TREATING EBV POSITIVE PRIMARY CNS POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE (PCNS-PTLD): RECOGNIZING THE ENTITY IN RENAL TRANSPLANT PATIENTS

摘要

PCNS-PTLD is a rare complication following solid organ transplantation (SOT) and is a distinct entity from primary CNS lymphoma (PCNSL). With fewer than 100 cases reported since 1970, there is no standard of care for PCNS-PTLD. Existing data supports combining reduction of immunosuppression (RI), whole-brain radiotherapy, monoclonal antibody therapy, and systemic/IT chemotherapy. Treating kidney SOT (kSOT) 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 and flow cytometry is critical. We report two cases of mixed B/T-cell PTLD in kSOT patients >10 years on immunosuppression (steroids, mycophenolate, tacrolimus/sirolimus) who presented with focal and cognitive neurologic deficits. Brain MRI revealed multiple supra- and infratentorial lesions. Patients with confirmed CNS-isolated disease were treated with partial-RI (off mycophenolate) and dexamethasone prior to initiation of rituximab (375mg/m2) x4 weekly cycles. With objective response, patients underwent consolidative rituximab therapy q21-days x4 cycles and restaged. Residual enhancing lesions were treated by stereotactic radiosurgery along with 2-4 cycles of temozolomide chemotherapy (150mg/m2) days 1-5 on a 28-day cycle. With this strategy, both patients achieved a complete response. PCNS-PTLD long-term survival is one distinguishing feature from PCNSL. With multiple treatment obstacles in kSOT PTLD, maximized targeting and step-wise addition of minimally toxic regimens can improve patient outcomes. This data challenges traditional paradigms about diagnosis and treatment of PTLD, specifically EBV+ disease occurring >6 years post SOT. We propose that the brain’s specialized immune microenvironment permits EBV driving of neoplastic progression and that this process is particularly sensitive to B-cell targeting concurrent with partial restoration of host immunity achieved by minimal RI. Subsequent SRS, temozolomide therapy, and partial immunosuppression helps maintain patient quality-of-life and reduce risk for allograft rejection.