Incidence of valganciclovir‐related leukopenia and neutropenia in solid organ transplant recipients at high risk of cytomegalovirus disease

Abstract

BackgroundValganciclovir (VGCV) prophylaxis is associated with an increased risk of hematologic side effects. We analyzed the impact of VGCV prophylaxis on leukopenia and neutropenia rates and explored risk factors for its occurrence.MethodsRetrospective cohort study of adult cytomegalovirus (CMV)‐seronegative solid organ transplantation (SOT) recipients of either CMV‐seropositive (CMV D+/R‐) or CMV‐seronegative (CMV D‐/R‐) donors between July 2005 and March 2019. CMV D+/R‐ SOT recipients received 3–12 months of VGCV prophylaxis whereas CMV D‐/R‐ SOT recipients received no VGCV prophylaxis. Competing risk regression was used to calculate risk factors for significant neutropenia (neutrophil count < 1000/μL).ResultsA total of 430 CMV‐seronegative SOT recipients (median age of 52.1 years, 76.5% males) were included, of which 203 (47.2%) were CMV D+/R‐ and 227 (52.8%) CMV D‐/R‐. The unadjusted incidence rate ratio of significant neutropenia attributable to VGCV exposure in the first year post‐transplant was 13.50 (95% confidence interval 7.36–27.11). Acute rejection occurred more frequently in neutropenic patients at 32.5% compared to 19.1% in those without neutropenia (p = .033). On multivariate analysis, VGCV prophylaxis for 1–90 days and 91–180 days versus no VGCV were the strongest risk factors for significant neutropenia with a sub‐distribution hazard ratio of 39.6 (95% CI, 8.57–182.6) and 13.2 (95% CI, 5.46–32.0), respectively.ConclusionsVGCV prophylaxis is limited by high rates of neutropenia. Future prospective studies are needed to assess alternative CMV prophylactic strategies in SOT recipients. image

Valganciclovir and Risk for Neutropenia: When the Friend Becomes the Foe

“…Studies in adult transplant recipients receiving valganciclovir 900 mg daily showed similar exposure to 5 mg/kg IV ganciclovir, the typical CMV prophylaxis dose, aiding the transition to enteral therapy [3]. However, reports of myelosuppression surfaced [3,4]. Pediatric dosing challenges arose, with initial weight-based regimens potentially causing under-exposure [5].…”