Cytotoxic T‐lymphocyte therapy for post‐transplant lymphoproliferative disorder after solid organ transplantation in children

Abstract

EBV-CTL immunotherapy targets EBV antigens expressed by tumor cells in PTLD. Data on outcome of EBV-CTL in pSOT patients are limited. The aim of the study is to describe our experience with allogeneic, third-party EBV-CTL for the treatment of PTLD in pSOT patients in a single tertiary center. Retrospective review was performed of all pSOT patients who received EBV-CTL for PTLD. PTLD was diagnosed using World Health Organization histologic criteria. EBV-CTLs were derived from human leukocyte antigen-typed, EBV-seropositive third-party donors, and cryopreserved and maintained by an accredited national blood transfusion service. Ten patients received EBV-CTL for histologically proven PTLD from 1999 to 2016 following liver (n=5), combined intestinal/liver (n=4), and liver/kidney (n=1) transplantation. PTLD occurred at median age of 40 months (range: 12-144) and median post-transplant interval of 8 months (range: 2-107). Seven had monomorphic, two had polymorphic, and one had Hodgkin-type PTLD. All were of B-cell origin and EBV-positive on histology. EBV-CTL achieved an overall remission rate of 80% (8 of 10). Transient adverse effects included fever, tachycardia, and vomiting. None developed graft-versus-host disease or opportunistic infections. EBV-CTL is an effective treatment for PTLD in pSOT patients, with good remission rate and minimal toxicity.

Post‐transplant lymphoproliferative disorder in pediatric intestinal transplant recipients: A literature review

“…EBV‐directed T cells, including donor‐derived, autologous, or HLA‐matched third party, are produced to target proliferating cells expressing EBV viral proteins in latency stage III (LMP1 and LMP2) . As the allograft is from a cadaveric donor and PTLD is generally of recipient origin, donor‐derived CTLs are not feasible or effective in intestinal transplant patients, but third‐party CTLs have been used successfully . The COG study ANHL1522 will determine the feasibility of treating solid organ transplant recipients with PTLD (EBV‐positive, CD20‐positive) with third‐party latent membrane protein‐specific T cells.…”

Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation

“…Of these, 4 achieved durable CR (17,30). Subsequently, limited case series have used third-party EBV-specific or multivirus-specific T cells to treat EBV-associated lymphoproliferative disorder (EBV-LPD) or EBV viremia complicating cord blood or marrow HCTs, SOTs, or genetic immune deficiencies (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) (summarized in Table 1). However, the number of patients treated for EBV + lymphoma is small.…”

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

“…Responses were better in those patients receiving EBV-CTLs that were matched at a higher number of HLA alleles and that had a higher fraction of CD4-positive T cells [91] . Another 5 patients treated with third-party EBV-CTLs resulted in four responders [92,93] , and ten pediatric SOT recipients produced an 80% overall remission rate [94] . A third-party, allogeneic, off-the-shelf bank of 330 GMP-grade EBV-CTL lines from specifically 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] .…”