Search

Background: Cytomegalovirus (CMV) is a driver of negative outcomes after lung transplant (LTX) and primary prophylaxis (PPX) with valganciclovir (VGC) is standard-of-care. VGC is associated with myelosuppression, prompting interest in letermovir (LTV)., Methods: Adults receiving LTX between April 1, 2015, and July 30, 2022, at our institution were evaluated. Patients were excluded if low CMV risk (D-/R-), survived <90 days post-LTX, or transferred care before PPX withdrawal. Primary outcomes were leukopenia (white blood cell count [WBC] ≤ 3.0 × 10 9 /L), severe leukopenia (WBC ≤ 2.0 × 10 9 /L), and neutropenia (absolute neutrophil count ≤ 1500 cells/µL) requiring granulocyte-colony stimulating factor (GCSF) on PPX. Secondary outcomes included breakthrough CMV infection and post-PPX CMV infection., Results: 204 patients met inclusion criteria: 175 patients on VGC and 29 patients on LTV (after VGC conversion). Most patients received bilateral LTX (62.7%) with non-lymphocyte-depleting induction (96.6%) and moderate-risk serostatus (D+/R+, 48.5%). Patients transitioned from VGC to LTV after a mean of 178 days (SD 80.8 days) post-transplant. Patients on VGC experienced significantly more leukopenia (82.3% vs. 58.6%, p = 0.008), severe leukopenia (57.1% vs. 31.0%, p = 0.016), and neutropenia requiring GCSF (70.9% vs. 51.7%, p = 0.048). Breakthrough (5.7% vs. 3.4%, p = 0.955) and post-PPX (24.6% vs. 37.9%, p = 0.199) infections were similar. A subgroup analysis of patients with high-risk serostatus showed similar trends, though did not reach statistical significance., Conclusions: In this single-center study, the incidence of leukopenia and neutropenia requiring GCSF were reduced with LTV compared to VGC. Breakthrough and post-PPX infections were not significantly different. This evidence suggests that LTV has comparable efficacy with reduced myelosuppression compared to VGC in LTX recipients, and may be an appropriate alternative for PPX., (© 2024 Wiley Periodicals LLC.)

Purpose: To evaluate epidemiology, risk-factors, and outcomes of high-level (HL) cytomegalovirus (CMV) viremia in liver transplant recipients., Methods: Adult patients receiving a liver transplant between 1/1/2017 and 9/30/2020 were evaluated. Viral loads at University of Wisconsin Health Clinical Laboratories were required to allow for numerical comparison. Primary objective was incidence and outcomes of HL CMV viremia (viral-load > 100 000 IU/ml). Secondary objective was to elucidate risk factors to allow targeted interventions., Results: Two hundred nine patients met inclusion criteria; 175 kept their graft for at least 240 days. Of these nine patients developed HL CMV, 28 developed low-level (LL CMV, viral-load 250-100 000 IU/ml), and 138 did not develop CMV viremia. When comparing these three groups via classic statistical methods time from transplant to viremia was similar (HL 158 ± 77 days, LL 150 ± 76 days). Clinical factors were also similar with the exception of donor seropositivity (HL 87.5%, LL 70.4%, No CMV 49.6%, p = 0.025). HL CMV was significantly associated with graft loss (p < 0.0001) on Kaplan-Meier analysis; graft loss in the LL CMV group did not differ from the no CMV group (p = 0.96). To allow valid assessment of risk factors in the total study population (n = 209), models of time-varying covariates were used, and Cox proportional hazards ratios were calculated. In this analysis, HL CMV was associated with a significantly increased risk of graft loss (HR 5.6, p = 0.0016). When investigating risk factors associated with HL CMV, donor seropositivity significantly increased risk (HR 8.85, 95% CI 1.13-71.43, p = 0.038). Pretransplant total bilirubin (HR 1.04, 95% CI 0.998-1.07, p = 0.06) trended toward significance. Recipient seronegativity, liver disease, clinical and allocation model for end-stage liver disease (MELD), transplant surgery duration, age, sex, induction immunosuppression, and maintenance immunosuppression were not significantly associated with development of HL CMV., Conclusion: HL CMV after liver transplant is uncommon but is associated with a significantly increased risk of graft loss that is not present in those patients who develop LL CMV or do not develop CMV viremia. Given these negative graft effects, CMV stewardship interventions targeting recipients of CMV seropositive allografts are warranted. Future larger scale studies evaluating the potential role of other factors in risk stratification are needed., (© 2022 Wiley Periodicals LLC.)