Risk Factors for CMV Viremia and Treatment-Associated Adverse Events Among Pediatric Hematopoietic Stem Cell Transplant Recipients

Abstract

Background: Cytomegalovirus (CMV) causes substantial morbidity and mortality after hematopoietic stem cell transplantation (HSCT). There are limited data on risk factors for CMV viremia and the safety of antiviral medications used to treat CMV in children.

Methods: We conducted a single-center retrospective study of children who underwent HSCT between 2000 and 2016. We used log-logistic regression to evaluate associations between clinical characteristics and CMV-free survival at 100 days after HSCT. We compared the incidences of laboratory-defined adverse events (AEs) during treatment with ganciclovir and foscarnet.

Results: Among 969 children, the median (interquartile range) age was 6.5 (3.1-11.5) years, and 80% underwent allogeneic HSCT. Two hundred forty-four (25%) children developed CMV viremia. Older age (odds ratio [OR], 0.95; 95% CI, 0.92-0.98), male sex (OR, 0.71; 95% CI, 0.51-0.99), non-Black, non-White race (OR, 0.56; 95% CI, 0.36-0.87), umbilical cord blood donor source (OR, 0.28; 95% CI, 0.08-0.97), and CMV seropositivity (R-/D+: OR, 0.17; 95% CI, 0.07-0.41; R+/D-: OR, 0.14; 95% CI, 0.09-0.21; R+/D+: OR, 0.08; 95% CI, 0.04-0.15) were associated with lower odds of 100-day CMV-free survival. Compared with foscarnet, ganciclovir was associated with lower incidences of thrombocytopenia (incidence rate ratio [IRR], 0.38; 95% CI, 0.15-0.97), electrolyte AEs (IRR, 0.42; 95% CI, 0.24-0.75), endocrine AEs (IRR, 0.52; 95% CI, 0.34-0.79), and renal AEs (IRR, 0.36; 95% CI, 0.19-0.65).

Conclusions: CMV viremia occurred commonly among children after HSCT, and ganciclovir and foscarnet were associated with distinct toxicity profiles among children with CMV infection. These findings should be considered when developing CMV prevention and treatment strategies for children after HSCT.

Keywords: antivirals; cytomegalovirus viremia; foscarnet; ganciclovir; immunocompromised children.

Figure 1.

Incidence of adverse events among children with CMV viremia by antiviral treatment. For the selected AEs, the incidence rates per 1000 patient-days are shown by antiviral treatment during episodes of CMV viremia. Electrolyte AEs include hyponatremia, hypernatremia, hypokalemia, hyperkalemia, low bicarbonate, high bicarbonate, hypocalcemia, and hypercalcemia; endocrine AEs include hypoglycemia and hyperglycemia; GI AEs include aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, elevated conjugated bilirubin, elevated gamma-glutamyl transferase, and elevated lipase; and renal AEs include elevated blood urea nitrogen and elevated creatinine. Error bars represent 95% CIs. Abbreviations: AEs, adverse events; CMV, cytomegalovirus; GI, gastrointestinal.

Figure 2.

Trends in laboratory values by day of antiviral therapy with ganciclovir and foscarnet. The changes in selected serum laboratory measures are shown over time by day of therapy with ganciclovir or foscarnet. Points represent the change from the baseline laboratory value at the start of therapy. Fitted lines were estimated by the restricted maximum likelihood, with error shading representing 95% CIs. A, Serum aspartate aminotransferase. B, Serum alanine aminotransferase. C, Serum alkaline phosphatase. D, Blood urea nitrogen. E, Serum creatinine. Abbreviations: ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; BUN, blood urea nitrogen.