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. 2023 Oct;25(5):e14104.
doi: 10.1111/tid.14104. Epub 2023 Jul 12.

Cytomegalovirus Immune reconstitution in cord blood transplant recipients on letermovir prophylaxis

Maheen Z Abidi  1 , Kyle C Molina  2   3 , Krystle Garth  4 , Jonathan A Gutman  5 , Adriana Weinberg  1   4   6
Affiliations

Cytomegalovirus Immune reconstitution in cord blood transplant recipients on letermovir prophylaxis

Maheen Z Abidi et al. Transpl Infect Dis. 2023 Oct.

Abstract

Introduction: Cytomegalovirus (CMV) can cause significant morbidity and mortality in cord blood transplant (CBT) recipients. Development of CMV-specific cell-mediated immunity (CMV-CMI) has been associated with protection against CMV clinically significant reactivation (CsCMV). In this study, we evaluated CMV-CMI reconstitution during letermovir prophylactic therapy, which prevents CsCMV without complete suppression of CMV reactivation.

Methods: We measured CMV-CMI in CMV-seropositive CBT recipients pre-transplant after Day+90 of letermovir prophylaxis and at Days +180, and +360- post-transplant using a dual color CMV-specific IFNγ/IL2 FLUOROSpot. CsCMV and nonCsCMV reactivations were abstracted from medical records. CsCMV was defined as CMV viral load ≥5,000 IU/ml using a whole blood assay.

Results: Among 70 CBT recipients, 31 developed CMV-CMI by Day+90 and an additional eight and five participants by Days +180 and +360, respectively. Thirty-eight participants developed CMV reactivation, including nine with CsCMV. Most reactivations (33 of 38) occurred before Day+180. Early CMV-CMI was present in six out of nine participants with CsCMV, indicating a lack of protection against CsCMV. Moreover, the magnitude of CMV-CMI at Day+90 did not differ between participants with CsCMV and nonCsCMV.

Conclusion: Approximately 50% of CBT recipients reconstituted CMV-CMI during letermovir prophylactic therapy. However, CMV-CMI did not reach levels protective against CsCMV. Extension of CMV prophylaxis beyond Day+90 may be considered in CMV-seropositive CBT recipients.

Keywords: cytomegalovirus; immune reconstitution; letermovir.

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Conflict of interest statement

Conflict of Interest/ Disclosures

This study was supported by an investigator-initiated research grant from Merck & Co, Inc. AW receives research grants from GSK and honoraria from GSK and Seqirus.

Figures

Figure 1.
Figure 1.. IFN-γ and IL-2 CMV-Specific Responses by Study Timepoints.
See this image and copyright information in PMC

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