Important Considerations in the Diagnosis and Management of Post-transplant Lymphoproliferative Disorder

Purpose of ReviewA relative lack of molecular and clinical studies compared to other lymphoid cancers has historically made it difficult to determine optimal management approaches in post-transplant lymphoproliferative disorder (PTLD). We sought to better define the state of the science in PTLD by examining recent advances in risk assessment, genomic profiling, and trials of PTLD-directed therapy.Recent FindingsSeveral major clinical trials highlight risk-stratified sequential therapy incorporating rituximab with or without chemotherapy as a rational treatment strategy in patients with CD20+ PTLD who do not respond to reduction of immunosuppression alone. Epstein Barr virus (EBV)-targeted cytotoxic lymphocytes are a promising approach in patients with relapsed/refractory EBV+ PTLD, but dedicated clinical trials should determine how autologous chimeric antigen receptor T cell therapy (CAR-T) may be safely administered to PTLD patients.Sequencing studies underscore the important effect of EBV infection on PTLD pathogenesis, but comprehensive genomic and tumor microenvironment profiling are needed to identify biomarkers that predict response to treatment in this clinically heterogeneous disease.

Automated summary

This review examines recent advances in risk assessment, genomic profiling, and trials of PTLD-directed therapy to better understand the state of the science in PTLD. Clinical trials have shown that rituximab-based sequential therapy is a rational treatment strategy for CD20+ PTLD patients who do not respond to reduction of immunosuppression alone. EBV-targeted cytotoxic lymphocytes and CAR-T cell therapy show promise, but further trials are needed to establish their safety and efficacy in PTLD patients.