Surveillance of CMV Terminase Gene Mutations in Allogeneic Hematopoietic Stem Cell Transplant Recipients Receiving Letermovir Prophylaxis

Figures

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  Figure 1. Flowchart of the study. Number of patients and total samples for each group. *Five patients received both primary and secondary prophylaxes, and were then included in both groups. **One sample of patient #1 during PP is not included in the group as the first sequencing of UL56 was performed only using the Sanger technique at the CMV National Reference Center. Other samples were tested using NGS.

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  Figure 2. CMV detection during primary and secondary prophylaxis. Among all patients, the pie chart depicts the proportions of patients (A) with no detectable CMV in light gray, at least one CMV DNA value < 3 log IU/mL in dark gray, or at least one CMV DNA value ≥ 3 log IU/mL in black, during primary (left) and secondary (right) prophylaxis. Among patients with positive CMV detection, the pie chart depicts (B) the proportions of samples with no detectable CMV in light gray, CMV DNA < 3 log IU/mL in dark gray, or CMV DNA ≥ 3 log IU/mL in black, during primary (left) and secondary (right) prophylaxis.

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  Figure 3. CMV DNA loads in patients with at least one positive CMV detection. Box plots display the median and interquartile range of CMV DNA loads during primary (light gray) or secondary letermovir prophylaxis (dark gray). Panel (A) includes all positive CMV DNA values, panel (B) includes only values ≥ 3 log IU/mL.

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  Figure 4. CMV viremia, antiviral treatments and mutations in the CMV terminase complex genes. Evolution of CMV DNA loads and mutations in CMV terminase complex genes over time after alloHSCT in patients who had CMV positive detection during primary (patients #1, 3, 4, and 5) and secondary (patient 2) letermovir prophylaxis. CMV loads are represented by dark circles. Periods with antiviral treatment are outlined in gray (GCV = ganciclovir, LMV = letermovir, FCV = foscarnet). Circled numbers correspond to samples with interpretable CMV sequencing. Polymorphism and resistance mutations detected are reported with their proportion compared to wild amino acid for each gene of the CMV terminase complex. Amino acid substitutions previously reported to confer letermovir resistance are formatted in bold. Mutations located at known resistance‐associated positions unreported yet and frameshifts (fs) and are underlined. *In patient # 1, the first detection of the mutation R369M in UL56 was found using a Sanger sequencing technique and could not be retested using the NGS technique.