Abstract

The treatment of post-transplant lymphoproliferative disorders (PTLD) significantly improved in the last two decades due to better understanding of the pathology, the identification of risk factors and the improvement of monitoring of EBV-DNAemia. PTLD represents a heterogeneous group of lymphoproliferative diseases that develop in the setting of immunosuppression following transplantation, including allogeneic stem cells (allo-SCT) and solid organ transplantation (SOT). Epstein-Barr virus (EBV) is responsible for almost all cases of PTLD post allo-SCT and for approximately 50% of those arising after SOT. In the last decade, EBV-specific cytotoxic T lymphocytes (EBV-CTLs) emerged as effective treatment for relapse/refractory (R/R) PTLD cases. In December 2022 European Medicine Agency (EMA) approved tabeleucleucel, an allogeneic EBV-CTLs, as second-line treatment for R/R EBV-PTLD cases after at least one line of therapy. Subsequently, a growing body of evidence showed the efficacy of this cellular product such as the phase III ALLELE study in which emerged the high efficacy and low toxicity of tabeleucleucel. The therapeutic armamentarium of R/R PTLD cases could further expand with the introduction of chimeric antigen receptor (CAR) T-cell, a cellular strategy which demonstrated a significant efficacy in the treatment of B lymphomas. In this mini review we focused on the cell-based treatment for R/R PTLD highlighting tabeleucleucel as a second-line approach and reporting the emerging scientific evidence with CAR-T which can play a strategic role in the evolving therapeutic algorithm.

Abbreviations:PTLD: Post-transplant Lymphoproliferative Disorders; EBV: Epstein-Barr Virus; Allo-SCT: Allogeneic Stem Cell Transplantation; SOT: Solid Organ Transplantation; EBV-CTLs: EBV-specific Cytotoxic T Lymphocytes; CAR-T: Chimeric Antigen Receptor T-cell