An Analysis of Routine Pretransplant Cytomegalovirus (CMV) DNA PCR Surveillance in CMV-Seronegative Recipients Undergoing Hematopoietic Cell Transplantation (HCT)

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Introduction Pre-HCT CMV reactivation occurs in 11% of CMV-seropositive allogeneic HCT candidates (Zamora et al. Blood Advances. 2024). The incidence of clinically significant primary CMV infection prior to allogeneic HCT in CMV-seronegative patients is unknown. In 2009, the Fred Hutchinson Cancer Center instituted routine CMV DNA PCR surveillance of all CMV-seronegative patients during the pre-HCT work-up period. Objective To determine the incidence of primary CMV infection in CMV-seronegative patients undergoing allogeneic HCT at our center. Methods CMV-seronegative patients who underwent allogeneic HCT between Apr-2009 and Dec-2023 were included in the current study. Plasma CMV DNA PCR surveillance was performed during the pre-HCT work-up period. Repeat testing was recommended in patients with low-level positive results, and treatment was recommended for persistently positive CMV DNAemia. Additional in-depth review of the electronic medical record was performed in patients with positive pre-HCT CMV DNA PCR tests to identify potential exposures such as blood products. Results Eleven of 1463 (0.8%) CMV-seronegative HCT recipients had pre-HCT CMV DNA detected by PCR (Figure 1). One patient had multiple positive pre-HCT CMV DNA PCR tests including a positive bronchoalveolar lavage (patient 1, Table 1). Upon further review, the patient had a positive CMV serologic result 8 months before admission to the transplant center at the time of underlying diagnosis, likely indicating a false negative pre-HCT CMV serology. The remaining 10 patients had a single, low-level positive CMV DNA PCR test a median of 18 days (IQR 14-73 days) prior to HCT with a median viral load of 20 IU/mL (IQR 14.1-36.3 IU/mL). Seven of the 10 patients received blood products prior to CMV DNA PCR positivity. No clinically significant primary CMV infection was detected (Table 1). Conclusion Pre-HCT CMV DNA detection in CMV-seronegative HCT recipients is rare. Most cases appear to be due to abortive CMV DNAemia, possibly associated with blood transfusions and, occasionally, in the context of CMV serostatus misclassification due to a loss of CMV IgG seroreactivity prior to HCT. Thus, routine CMV DNA PCR surveillance prior to HCT is of low yield. Alternative strategies to consider include targeted pre-HCT surveillance of CMV-seronegative patients with a specific exposure risk (e.g. close contact to small children who attend group daycare) and serologic testing at the time of underlying diagnosis to identify patients who may lose serologic evidence of CMV infection before HCT.

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