Third-party CMV- and EBV-specific T-cells for first viral reactivation after allogeneic stem cell transplant

Jiang, W; Clancy, LE; Avdic, S; Sutrave, G; Street, J; Simms, R; McGuire, HM; Patrick, E; Chan, AS; McCaughan, G; Myers, N; Micklethwaite, KP; Antonenas, V; Selim, AG; Ritchie, D; Bateman, CM; Shaw, PJ; Blyth, E; Gottlieb, DJ

Author(s): Jiang, W; Clancy, LE; Avdic, S; Sutrave, G; Street, J; Simms, R; McGuire, HM; Patrick, E; Chan, AS; McCaughan, G; Myers, N; Micklethwaite, KP; Antonenas, V; Selim, AG; Ritchie, D; Bateman, CM; Shaw, PJ; Blyth, E; Gottlieb, DJ;
Details: Publication Year 2022-09-13,Volume 6,Issue #17,Page 4949-4966
Journal Title: Blood Advances
Publication Type: Research article
Abstract: Virus-specific T-cells (VSTs) from third-party donors mediate short- and long-term antiviral effects in allogeneic hematopoietic stem cell transplant (HSCT) recipients with relapsed or refractory viral infections. We investigated early administration of third-party VSTs, together with antiviral therapy in patients requiring treatment for first cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection. Thirty HSCT patients were treated with 1 to 4 VST infusions (2 x 107 cells/m2; CMV n=27, EBV n=3) at a median of 4 days after initiation of antiviral treatment. The overall viral response rate was 100%, with a complete response (CR) rate of 94%. Of the 28 patients who achieved a CR, 23 remained virus PCR negative (n=9) or below quantitation limit (n=14) for the duration of follow-up. Four patients had brief episodes of quantifiable reactivation not requiring additional therapy, and one required a second infusion after initial CR, remaining PCR negative thereafter. All 3 patients treated for EBV post-transplant lymphoproliferative disorder achieved sustained CR. Rates of aGVHD and cGVHD after infusion were 13% and 23%, respectively. There were no serious infusion-related adverse events. VST infusion was associated with rapid recovery of CD8+CD45RA-CD62L- and a slower recovery of CD4+CD45RA-CD62L- effector memory T-cells; CMV-specific T-cells comprised up to 13% of CD8+ cells. At 1 year post-transplant, non-relapse mortality was 10%, cumulative incidence of relapse was 7%, overall survival was 88% and 25 of 27 patients had ECOG status of 0 or 1. Early administration of third-party VSTs in conjunction with antiviral treatment appears safe and leads to excellent viral control and clinical outcomes. Registered on Australian New Zealand Clinical Trials Registry as #ACTRN12618000343202.
Keywords: Antiviral Agents; Australia; Cytomegalovirus; *Cytomegalovirus Infections/etiology/therapy; *Epstein-Barr Virus Infections/etiology; *Hematopoietic Stem Cell Transplantation/adverse effects; Herpesvirus 4, Human; Humans; Stem Cell Transplantation/adverse effects; Transplantation, Homologous/adverse effects
Department(s): Haematology
PubMed ID: 35819448
Publisher's Version: https://doi.org/10.1182/bloodadvances.2022007103
Open Access at Publisher's Site: https://doi.org/10.1182/bloodadvances.2022007103
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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