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Review
. 2024 Feb 17;78(2):423-429.
doi: 10.1093/cid/ciad550.

Revisiting Cytomegalovirus Serology in Allogeneic Hematopoietic Cell Transplant Recipients

Vera Portillo  1 , Stavroula Masouridi-Levrat  2 , Léna Royston  1 , Sabine Yerly  3 , Manuel Schibler  1   3 , Maria Mappoura  2 , Sarah Morin  2 , Federica Giannotti  2 , Anne-Claire Mamez  2 , Christian van Delden  1 , Yves Chalandon  2 , Dionysios Neofytos  1
Affiliations
Review

Revisiting Cytomegalovirus Serology in Allogeneic Hematopoietic Cell Transplant Recipients

Vera Portillo et al. Clin Infect Dis. .

Abstract

Background: Allogeneic hematopoietic cell transplant recipients (allo-HCTRs) with positive cytomegalovirus (CMV) serology may have false-positive results due to blood product transfusion-associated passive immunity.

Methods: This single-center cohort study included allo-HCTRs with negative baseline (at malignancy diagnosis) CMV serology and indeterminate/low-positive (CMV IgG titer, ≥0.6-<50 U/mL) pretransplant CMV serology with negative pretransplant plasma CMV DNAemia. The CMV status of those patients was reclassified from R+ to R- (CMVR- reclassification group). We compared those patients to allo-HCTRs with negative (CMV IgG titer <0.6 U/mL) pretransplant CMV IgG (CMVR- group). We describe the number and type of patients whose pretransplant CMV status was reclassified from indeterminate/positive to negative. We reviewed all plasma CMV DNAemia tests performed during the first 6 months posttransplant in both groups to assess the safety of this approach.

Results: Among 246 (84.5%) of 291 transplanted patients identified as CMVR+ pretransplant, 60 (24.4%) were reclassified from CMV serology indeterminate (N:10)/low-positive (N:50) to R-. Only 1 of 60 patients (1.67%) in the CMVR- reclassification group versus 3 of 44 (6.8%; P = .30) in the CMVR- group developed CMV DNAemia during the follow-up period. There were no significant differences in the number of CMV DNAemia tests performed, CMV DNAemia range, and time posttransplant between the 2 groups.

Conclusions: One of 4 allo-HCT CMVR+ may be falsely flagged as R+, with significant impact on donor selection and prophylaxis administration. A 2-step approach including CMV serology testing at hematologic malignancy diagnosis in allo-HCT candidates and careful review of pretransplant CMV IgG titers may help correctly classify CMV serology status.

Keywords: CMV; CMV serology; allogeneic hematopoietic cell transplantation; false-positive; letermovir‌.

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Conflict of interest statement

Potential conflicts of interest. L. R. is a postdoctoral fellow supported by the Swiss National Science Foundation (SNSF) and the Canadian Institutes of Health Research (CIHR-CNT). Y. C. reports honoraria for participation in symposia and advisory boards from MSD, Novartis, Incyte, BMS, Pfizer, AbbVie, Roche Diagnostics, Jazz, Gilead, Amgen, Astra-Zeneca, and Servier and travel support from MSD, Roche Diagnostics, Gilead, Amgen, Incyte, AbbVie, Janssen, Astra-Zeneca, Jazz, and Sanofi all to their institution. D. N. reports research support from MSD and Pfizer; consulting fees from Roche Diagnostics, MSD, Pfizer, Basilea, Takeda, and Gilead; payment or honoraria for educational/speaking events from Pfizer, MSD, Gilead, and Takeda; and travel support from Pfizer, MSD, and Gilead. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/revisiting-cytomegalovirus-serology-in-allogeneic-hematopoietic-cell-transplant-recipients-e66f73fb-8238-44cb-a4b4-b9859f8c7682
Figure 1.
Figure 1.
Study flowchart. Abbreviation: CMV, cytomegalovirus.
Figure 2.
Figure 2.
Proposed algorithm to safely reclassify allogeneic hematopoietic cell transplant recipients from CMV-positive to CMV-negative, in case of baseline (at the time of diagnosis of hematologic malignancy) negative CMV serology, indeterminate or low-positive pretransplant CMV IgG titers, and negative pretransplant plasma CMV DNAemia. Abbreviations: CMV, cytomegalovirus; IgG, immunoglobulin G.
See this image and copyright information in PMC

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