Another tool against cytomegalovirus after allogeneic hematopoietic cell transplantation
George L. Chen, Elizabeth J. Shpall
George L. Chen, Elizabeth J. Shpall
Published May 15, 2023
Citation Information: J Clin Invest. 2023;133(10):e170282. https://doi.org/10.1172/JCI170282.
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Commentary

Another tool against cytomegalovirus after allogeneic hematopoietic cell transplantation

Abstract

Cytomegalovirus (CMV) viremia from reactivation of latent infection is a common complication after allogeneic hematopoietic cell transplantation (HCT). Untreated, CMV viremia can progress to affect other organs, resulting in organ dysfunction with high morbidity and mortality. In this issue of the JCI, Prockop and authors demonstrate that third-party donor T cells sensitized ex vivo to CMV pp65-derived overlapping pentadecapeptides are safe and effective for the treatment of CMV reactivation or CMV disease refractory to first-line pharmacotherapies occurring after HCT. They also provide insight into the biological differences between responders and nonresponders. This work confirms the utility of third-party CMV pp65 VSTs and suggests strategies for further improving the efficacy of this cell-therapy approach.

Authors

George L. Chen, Elizabeth J. Shpall

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Figure 1

Treatments for CMV therapy after HCT depend on patient status and disease severity.

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Treatments for CMV therapy after HCT depend on patient status and diseas...
(A) CMV-seronegative recipients (R–) of CMV-seronegative donor cells (D–) are at the lowest risk for subsequent CMV reactivation. All other combinations are at increased risk. CMV can reactivate in at-risk patients, resulting in CMV viremia. Untreated, CMV viremia can progress to CMV disease. CMV reactivation can be prevented with letermovir. CMV-specific antivirals can treat CMV reactivation to prevent CMV disease as well as treat CMV disease. CMVpp65-VSTs provide another possible modality for treating CMV reactivation and disease. (B) In HCT, recipients initially receive stem cell grafts from allogeneic donors. VSTs can come from the original donor or from a third-party donor distinct from the original donor or recipient.