Zamora, Danniel and Duke, Elizabeth R. and Xie, Hu and Edmison, Bradley C. and Akoto, Brenda and Kiener, Richard and Stevens-Ayers, Terry and Wagner, Ralf and Mielcarek, Marco and Leisenring, Wendy M. and Jerome, Keith R. and Schiffer, Joshua T. and Finak, Greg and De Rosa, Stephen C. and Boeckh, Michael (2021) Cytomegalovirus-specific T-cell reconstitution following letermovir prophylaxis after hematopoietic cell transplantation. BLOOD, 138 (1). pp. 34-43. ISSN 0006-4971, 1528-0020
Full text not available from this repository. (Request a copy)Abstract
Decreased cytomegalovirus (CMV)-specific immunity after hematopoietic cell transplantation (HCT) is associated with late CMV reactivation and increased mortality. Whether letermovir prophylaxis-associated reduction in viral exposure influences CMV-specific immune reconstitution is unknown. In a prospective cohort of allogeneic HCT recipients who received letermovir, we compared polyfunctional CMV-specific T-cell responses to those of controls who received PCR-guided preemptive therapy before the introduction of letermovir. Thirteen-color flow cytometry was used to assess T-cell responses at 3 months after HCT following stimulation with CMV immediate early-1 (IE-1) antigen and phosphoprotein 65 (pp65) antigens. Polyfunctionality was characterized by combinatorial polyfunctionality analysis of antigen-specific T-cell subsets. Use of letermovir and reduction of viral exposure were assessed for their association with CMV-specific T-cell immunity. Polyfunctional T-cell responses to IE-1 and pp65 were decreased in letermovir recipients and remained diminished after adjustment for donor CMV serostatus, absolute lymphocyte count, and steroid use. Among letermovir recipients, greater peak CMV DNAemia and increased viral shedding were associated with stronger CD8(+) responses to pp65, whereas the CMV shedding rate was associated with greater CD4(+) responses to IE-1. In summary, our study provided initial evidence that letermovir may delay CMV-specific cellular reconstitution, possibly related to decreased CMV antigen exposure. Evaluating T-cell polyfunctionality may identify patients at risk for late CMV infection after HCT.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IN-VITRO; IMMUNE RECONSTITUTION; PREEMPTIVE THERAPY; IDENTIFY PATIENTS; LONG-TERM; RECIPIENTS; INFECTION; DISEASE; IMPACT; GANCICLOVIR; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Sep 2022 07:01 |
| Last Modified: | 12 Sep 2022 07:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47128 |
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