Cytomegalovirus IL‐10 in Plasma as a Marker of Active Infection in Allogeneic Hematopoietic Transplant Recipients: An Exploratory Study

TL;DR

This study explores whether measuring CMV IL-10 in plasma can help detect active CMV infection in transplant patients, even when they are on a specific drug.

Contribution

The study introduces cmvIL-10 as a potential biomarker for active CMV replication in transplant recipients.

Findings

cmvIL-10 levels were significantly higher in clinically significant CMV episodes compared to non-significant ones.

cmvIL-10 AUC between Days 14 and 23 showed strong discrimination between clinically significant and non-significant CMV episodes in patients on LMV therapy.

A cutoff value of log10 3.06 for cmvIL-10 AUC achieved 100% sensitivity and specificity in predicting clinically significant CMV episodes.

Abstract

We investigated whether plasma cytomegalovirus (CMV) IL‐10 (cmvIL‐10) levels could serve as a biomarker of active CMV replication in allogeneic hematopoietic transplant recipients (allo‐HCT) in the presence or absence of letermovir (LMV) prophylaxis. A total of 189 leftover plasma samples that tested positive for CMV DNA (Alinity m CMV assay), representing 33 episodes of CMV DNAemia were run on a laboratory‐developed enzyme‐linked immunosorbent assay for cmvIL‐10 quantification. Eighteen episodes developed during LMV prophylaxis. Overall, 16 episodes of CMV DNAemia were classified as clinically significant (CsCMVi). There was an overall very weak correlation between the two biomarkers (Rho = 0.10; p = 0.16). Overall, the median cmvIL‐10 area under the curve (AUC) until CMV DNA levels reached their peak was significantly higher (p < 0.001) in CsCMVi episodes than in non‐CsCMVi episodes. cmvIL‐10 AUC between Days 14 and 23 after allo‐HCT (AUC₁₄₋₂₃) values were significantly higher in CsCMVi episodes compared with non‐CsCMVi episodes among patients receiving LMV therapy (p = 0.008). An AUC₁₄₋₂₃ cutoff value of log10 3.06 discriminated anticipately between CsCMVi and non‐CsCMVi with a sensitivity and specificity of 100%. Plasma cmvIL‐10 levels may reflect true CMV replication and thus provide a unique perspective on viral dynamics, serving as an ancillary marker to CMV DNA monitoring.

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