Post-transplant Lymphoproliferative Disorder Following Cardiac Transplantation.

Rabea Asleh,Alexandros Briasoulis,Sudhir S. Kushwaha,Hilmi Alnsasra,Thomas M. Habermann

doi:10.3389/fcvm.2022.787975

Abstract

Post-transplant lymphoproliferative disorder (PTLD) is a spectrum of lymphoid conditions frequently associated with the Epstein Barr Virus (EBV) and the use of potent immunosuppressive drugs after solid organ transplantation. PTLD remains a major cause of long-term morbidity and mortality following heart transplantation (HT). Epstein-Barr virus (EBV) is a key pathogenic driver in many PTLD cases. In the majority of PTLD cases, the proliferating immune cell is the B-cell, and the impaired T-cell immune surveillance against infected B cells in immunosuppressed transplant patients plays a key role in the pathogenesis of EBV-positive PTLD. Preventive screening strategies have been attempted for PTLD including limiting patient exposure to aggressive immunosuppressive regimens by tailoring or minimizing immunosuppression while preserving graft function, anti-viral prophylaxis, routine EBV monitoring, and avoidance of EBV seromismatch. Our group has also demonstrated that conversion from calcineurin inhibitor to the mammalian target of rapamycin (mTOR) inhibitor, sirolimus, as a primary immunosuppression was associated with a decreased risk of PTLD following HT. The main therapeutic measures consist of immunosuppression reduction, treatment with rituximab and use of immunochemotherapy regimens. The purpose of this article is to review the potential mechanisms underlying PTLD pathogenesis, discuss recent advances, and review potential therapeutic targets to decrease the burden of PTLD after HT.

Highlights

De novo malignancy is an important cause of long-term morbidity and mortality in solid organ transplant (SOT) recipients
Post-transplant lymphoproliferative disorder (PTLD) is a complication of chronic immunosuppression after heart transplantation (HT), related to Epstein–Barr virus (EBV) activation resulting in proliferation of EBV-positive B cells in most cases
Prevention of PTLD is important and this can be achieved with tapering immunosuppression, use of mammalian target of rapamycin (mTOR) inhibitors in lieu of calcineurin inhibitor (CNI), routine surveillance of EBV viral loads, in patients with EBV mismatch

Summary

INTRODUCTION

De novo malignancy is an important cause of long-term morbidity and mortality in solid organ transplant (SOT) recipients. PTLD After Cardiac Transplantation and the increasing number of older patients receiving HT [17], malignancy becomes relatively more important than other causes of morbidity and mortality post-transplant [18]. The rates of adult PTLD for heart and kidney transplants were 0.9 and 0.6%, respectively These rates were found to be lower in patients with EBV positive serology compared to those with negative serology [25]. Pediatric SOT recipients were noted to experience higher incidence of PTLD than adults, which can be attributed in large part to the development of primary EBV infection after transplantation [27, 28]. The incidence of EBV-negative PTLD was reported to be increasing over time in a cohort of 176 SOT recipients [29]. In adult kidney transplant recipients, PTLD rates were 0.6% in all serology, 1.7% in EBV-negative serology, and 0.5% in EBV-positive serology

RISK FACTORS

PTLD incidence

The Role of EBV

The Role of Immunosuppression

Findings

CONCLUDING REMARKS