Risk Factors Associated with Survival Following Ganciclovir Prophylaxis through Day +100 in Cytomegalovirus At-Risk Pediatric Allogeneic Stem Cell Transplantation Recipients: Development of Cytomegalovirus Viremia Associated with Significantly Decreased 1-Year Survival

Abstract

Cytomegalovirus (CMV) reactivation is a major cause of morbidity and nonrelapse mortality (NRM) in pediatric allogeneic stem cell transplantation (alloSCT) recipients. Approximately 80% of CMV seropositive alloHCT recipients will experience CMV reactivation without prophylaxis. The impacts of ganciclovir prophylaxis and subsequent CMV viremia on 1-year survival and 1-year NRM are unknown. The primary objective of this study was to determine the effect of CMV viremia on the probability of 1-year survival and 1-year NRM in pediatric alloSCT recipients receiving 100 days of ganciclovir prophylaxis. The secondary objective was to determine the effect of other risk factors on 1-year survival and 1-year NRM. All patients age 0 to 26 years who underwent alloSCT between June 2011 and May 2020 and received ganciclovir prophylaxis for 100 days at Westchester Medical Center, an academic medical center, were analyzed. Ganciclovir was administered to at-risk alloSCT recipients (donor and or recipient CMV+ serostatus) as 5 mg/kg every 12 hours from the first day of conditioning through day -1 (recipient CMV+ only) followed by 6 mg/kg every 24 hours on Monday through Friday beginning on the day of an absolute neutrophil count >750/mm3 and continuing through day +100. National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 criteria were used to grade toxicity. NRM was analyzed using competing survival analysis with relapse death as a competing event. The log-rank and Gray tests were performed to compare the 1-year survival probabilities and NRM cumulative incidence between patients who experienced CMV viremia post-alloSCT and those who did not. Univariate Cox regression analysis was performed for the following risk factors: CMV viremia, donor source, sex, malignant disease, disease risk index, conditioning intensity, receipt of rabbit antithymocyte globulin (rATG)/alemtuzumab, graft-versus-host disease (GVHD) prophylaxis, CMV donor/recipient serostatus, grade II-IV acute GVHD, and grade 3/4 neutropenia necessitating discontinuation of ganciclovir, treating the last 3 factors as time-dependent covariates. Those with P values < .2 were included in the multivariate Cox regression analysis. Eighty-four alloSCT recipients (41 males, 43 females; median age, 10.8 years [range, .4 to 24.4 years]) were analyzed. Multivariate analysis showed significantly lower 1-year survival and significantly higher 1-year NRM in patients who developed CMV viremia compared to those who did not (P=.0036). No other risk factors were significantly associated with 1-year survival or 1-year NRM. One-year survival was significantly decreased and 1-year NRM was significantly increased in pediatric alloSCT recipients who developed CMV viremia following ganciclovir prophylaxis. No other risk factors were found to be associated with 1-year survival or 1-year NRM. Alternative CMV prophylaxis regimens that reduce CMV viremia should be investigated in pediatric alloSCT recipients at risk for CMV infection.