EBV‐specific cytotoxic T lymphocytes for refractory EBV‐associated post‐transplant lymphoproliferative disorder in solid organ transplant recipients: a systematic review

Abstract

Summary The use of Epstein–Barr virus‐specific cytotoxic T lymphocytes (EBV‐CTLs) in adoptive immunotherapy in hematopoietic stem cell transplantation (HSCT) patients with post‐transplantation lymphoproliferative disorder (PTLD) has demonstrated safety and effectiveness. EBV‐CTLs might also be the effective treatment of refractory PTLD of solid organ transplantation (SOT) recipients. Two independent assessors searched Pubmed, Embase, Cochrane Library, and Web of Science from their inception to November 2020. Eleven studies with 76 patients (42, 55% male) were included. We extracted the data and completed the quality assessments. Most of the studies were from Europe and the USA. Liver and kidney transplantation accounted for most of the transplant types. Thirty‐five (46.1%) patients were diagnosed with monomorphic PTLD, and B lymphocyte type was the most common. All the patients received primary treatment for PTLD while it was ineffective. CTLs included autologous EBV‐CTLs (15/76, 22%) and HLA‐matched third‐party EBV‐CTLs (61/76, 78%). The response rate for EBV‐CTL treatment of refractory PTLD was 66%. Of 50 patients, 36 achieved complete remission and 14 achieved partial remission. EBV‐DNA level decreased in 39 patients. Adverse reactions were rare and mild. We conclude that adoptive therapy with EBV‐specific CTLs is safe, well‐tolerated, and effective in PTLD.

Management of Resistant Post-transplant Lymphoproliferative Disorder: CAR-T Is a New Option

“…The overall response obtained reached 66% (50/76); complete remission (CR) was achieved in 36/50 and partial remission (PR) in 14/50 patients. In 39/76 patients, EBV viremia was decreased, and no severe adverse reactions were reported (6).…”

Post‐transplant lymphoproliferative disorder: Update on treatment and novel therapies

“…All patients who received autologous EBV‐CTLs achieved CR compared to 48.4%–100% in those who received EBV‐CTLs from partially HLA‐matched third‐party donors. EBV‐DNA levels decreased in 39 patients and this correlated with response 56 . Only one patient developed grade 1 skin GvHD.…”

“…54 Although it has been reported that autologous EBV-CTLs can frequently eradicate SOT PTLD, they seem to be less efficient in clearing EBV viremia. 56,57 T A B L E 2 Summary of the major aspects of different types of EBV-cytotoxic T lymphocytes (EBV-CTLs).…”

Approach to acute kidney injury following paediatric kidney transplant

“…Those with PTLD should be referred to an oncologist for treatment. The use of rituximab as well as EBV-specific cytotoxic T-cells in the treatment of PTLD has been shown to be beneficial [42].…”