Abstract
Post-transplant lymphoproliferative disease (PTLD) remains a challenging and high-impact complication of kidney transplantation, requiring thoughtful prevention, timely recognition, and multidisciplinary management. Key strategies include careful selection of immunosuppressive regimens, particularly avoiding belatacept in Epstein-Barr virus (EBV)-seronegative recipients and exercising caution with lymphodepleting induction in EBV-mismatched pairs, along with targeted EBV surveillance in high-risk patients. Once PTLD is suspected or confirmed, accurate staging and a stepwise treatment approach beginning with reduction of immunosuppression and escalating to rituximab, chemotherapy, or advanced cellular therapies are essential, with EBV-CTLs and chimeric antigen receptor T-cell therapy offering promising options in refractory disease. Close monitoring for infectious complications, cytopenias, and rejection is critical throughout treatment. Importantly, a prior history of PTLD should not preclude future transplantation in appropriately selected patients with sustained remission. Continued research is needed to refine surveillance strategies, clarify optimal treatment sequencing, and improve long-term outcomes for kidney transplant recipients at risk for or affected by PTLD.