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.

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.

Safety and Effectiveness of Intravenous Pentamidine for Prophylaxis of Pneumocystis jirovecii Pneumonia in Pediatric Hematology/Oncology Patients.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection that can lead to significant morbidity and mortality in immunocompromised pediatric hematology/oncology patients. Trimethoprim/sulfamethoxazole is the gold standard for prophylaxis. Intravenous (IV) pentamidine is the preferred second-line agent for PCP prophylaxis at our institution and is used first-line under certain circumstances. The purpose of this study is to evaluate the effectiveness and safety of IV pentamidine for PCP prophylaxis in pediatric hematology/oncology patients. MATERIALS AND METHODS: A retrospective analysis of pediatric hematology/oncology patients (N=121) who received ≥1 dose of IV pentamidine between January 2009 and July 2014 was conducted. Electronic health records were reviewed to determine baseline characteristics, rate of breakthrough PCP infection, characteristics of IV pentamidine use, and adverse events. The follow-up period was 6 months after the last reported IV pentamidine dose or the last recorded clinic visit/hospital admission. RESULTS: No patients developed PCP during the entirety of their IV pentamidine course or during the follow-up period. Nineteen patients (16%) experienced adverse events and 5 of the 19 patients required discontinuation of IV pentamidine. CONCLUSIONS: IV pentamidine is a safe, tolerable, and effective agent for PCP prophylaxis in pediatric hematology/oncology patients and may be considered a reasonable therapeutic alternative when trimethoprim/sulfamethoxazole cannot be used for PCP prophylaxis.