Epstein-Barr virus-associated post-transplant lymphoproliferative disorders: beyond chemotherapy treatment.

Sanam Shahid,Susan E Prockop

doi:10.20517/cdr.2021.34

Abstract

Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening complication of both allogeneic solid organ (SOT) and hematopoietic cell transplantation (HCT). The histology of PTLD ranges from benign polyclonal lymphoproliferation to a lesion indistinguishable from classic monoclonal lymphoma. Most commonly, PTLDs are Epstein-Barr virus (EBV) positive and result from loss of immune surveillance over EBV. Treatment for PTLD differs from the treatment for typical non-Hodgkin lymphoma because prognostic factors are different, resistance to treatment is unique, and there are specific concerns for organ toxicity. While recipients of HCT have a limited time during which they are at risk for this complication, recipients of SOT have a lifelong requirement for immunosuppression, so approaches that limit compromising or help restore immune surveillance are of high interest. Furthermore, while EBV-positive and EBV-negative PTLDs are not intrinsically resistant to chemotherapy, the poor tolerance of chemotherapy in the post-transplant setting makes it essential to minimize potential treatment-related toxicities and explore alternative treatment algorithms. Therefore, reduced-toxicity approaches such as single-agent CD20 monoclonal antibodies or bortezomib, reduced dosing of standard chemotherapeutic agents, and non-chemotherapy-based approaches such as cytotoxic T cells have all been explored. Here, we review the chemotherapy and non-chemotherapy treatment landscape for PTLD.

Highlights

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of allogeneic solid organ (SOT) and hematopoietic cell (HCT) transplantation
In hematopoietic cell transplantation (HCT) recipients, the risk of PTLD resolves after reconstitution of donor-derived immunity, whereas in recipients of SOT long-term immunosuppression translates into a long-term risk of both Epstein-Barr virus (EBV)-positive and EBV-negative PTLD - ranging in histology from benign lymphoid hypertrophy to aggressive lymphoma
PTLD after SOT has a bimodal incidence with “early” PTLD developing within a year of transplantation and being nearly uniformly EBV-positive, and while there is a second peak of “late” more commonly EBV-negative PTLD five-to-ten years after transplant, it is increasingly evident that the risk of PTLD continues for as long as the patient remains on immunosuppression[1,6]

Summary

INTRODUCTION

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of allogeneic solid organ (SOT) and hematopoietic cell (HCT) transplantation. In the treatment of EBV-positive PTLD emerging after HCT, multi-agent chemotherapy use has been limited to patients with a demonstrated first response to rituximab[33]. Despite these challenges, several studies have demonstrated that autologous EBV-CTLs can be generated from recipients of SOT and when infused for treatment of EBV-positive PTLD, they can eradicate disease and restore EBV-specific immunity[86,87,88]. A third-party, allogeneic, off-the-shelf bank of 330 GMP-grade EBV-CTL lines from consented healthy EBV-seropositive HCT donors was used to treat 46 recipients of HCT (n = 33) or SOT (n = 13) with established EBV-positive PTLD, whose disease had failed to respond to or relapsed after rituximab therapy[27]. PTLD: Post-transplant lymphoproliferative disorder; EBV CTLs: Epstein-Barr virus cytotoxic T cell lines; CR: complete responses; PR: partial response; GVHD: graft-versus-host disease

Method of selection

CONCLUSION

Findings

Conflicts of interest