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, 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 (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 to foscarnet, ganciclovir was associated with lower incidences of thrombocytopenia (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.

Use of Maribavir for Multidrug Resistant Cytomegaloviremia in a Pediatric Oncology Patient

“…Antiviral treatment side effects need to be weighed against potential end-organ damage (pneumonitis, retinitis, uveitis, and colitis) with pervasive CMV viremia. 3 Primary CMV is somewhat more likely to result in end-organ damage than reactivation of disease; since no prior testing for CMV was performed in our patient, we were not able to determine if his illness was due to primary infection or reactivation. Most patients who develop CMV disease while on chemotherapy due not require long courses of antiviral therapies.…”

“…3 First-line therapies include ganciclovir or its isomer valganciclovir, both of which inhibit viral DNA polymerase. 3 Both medications are well tolerated in pediatric patients, but as seen with our patients, cytopenias commonly occur. The second-line therapy for CMV viremia is typically foscarnet, although reversible nephrotoxicity needs to be monitored closely.…”

Haematopoietic stem cell transplantation for hepatitis‐associated aplastic anaemia and non‐hepatitis‐associated aplastic anaemia: A propensity score‐matched analysis

“…It has been reported that CMV viraemia occurred commonly after HSCT with older age, male sex and CMV seropositivity associated with lower odds of 100‐day CMV‐free survival 31 . One transplant centre 30 has reported a high CMV viraemia incidence detected in 68.3% of SAA patients after HID‐HSCT (HID vs. MSD, 68.3% vs. 39.6%, p = 0.002) using in vivo T‐cell depletion (TCD) (ATG based).…”

“…It has been reported that CMV viraemia occurred commonly after HSCT with older age, male sex and CMV seropositivity associated with lower odds of 100-day CMV-free survival. 31 One transplant centre 30 has reported a high CMV viraemia incidence detected in 68.3% of SAA patients after HID-HSCT (HID vs. MSD, 68.3% vs. 39.6%, p = 0.002) using in vivo T-cell depletion (TCD) (ATG based). In this study, most patients and donors were CMV-IgG positive, and the incidence of CMV viraemia of HAAA patients with HID-HSCT was significantly higher (68.7% vs. 8.3%, p = 0.009).…”

Letermovir for Prophylaxis and Pre-emptive Therapy of Cytomegalovirus Infection in Paediatric Allogeneic Haematopoietic Cell Transplant Patients

“…It is associated with increased morbidity and mortality due to eventual progress to end-organ disease, including chorioretinitis, pneumonia, and gastrointestinal disease [3][4][5][6][7]. Cytomegalovirus-seropositivity of the recipient and/or the donor is the most important risk factor for CMV infection in adults [8,9] and is similarly associated with increased CMV infection rates in paediatric patients [7,10].…”