The Safety, Feasibility, and Efficacy of Ganciclovir Prophylaxis Through Day +100 in Pediatric Allosct Recipients: Bone Marrow Suppression Secondary to Ganciclovir May Limit Effectiveness

Author Type(s)

Faculty

Document Type

Abstract

Publication Date

2022

DOI

10.1038/s41409-022-01803-6

Journal Title

Bone Marrow Transplantation

Department

Medicine

Second Department

Pediatrics

Abstract

Background: CMV reactivation is a major cause of morbidity and non-relapse mortality (NRM) in alloSCT recipients. Approximately 80% of CMV seropositive recipients will experience CMV reactivation without prophylaxis. We previously described the incidence of toxicity and CMV viremia/disease in pediatric alloSCT recipients following ganciclovir prophylaxis through day +100 and impact on 1-year survival (p=0.002) (Klejmont/Cairo, et al. ASTCT, 2021). The impact of other risk factors on 1-year survival and 1-year non-relapse mortality (NRM) are unknown. The primary objective was to compare the probability of 1-year survival and 1-year NRM between patients who had grade III/IV neutropenia secondary to ganciclovir that was unresponsive to GCSF in pediatric alloSCT recipients and those who had not. Secondary objective was to determine impact of other risk factors on 1-year survival and 1-year NRM. Methods: All patients aged 0-26 y who underwent alloSCT between 6/2011-5/2020 and received ganciclovir prophylaxis were analyzed. Ganciclovir was administered to at-risk alloSCT recipients (CMV D+ and/or R+) as: 5mg/kg q12h from 1st day of conditioning through day -1 (CMV R+ only) followed by 6 mg/kg q24h M-F beginning when ANC > 750/mm3 through day +100. NCI CTCAE 5.0 criteria were used to grade toxicity. A cox regression univariate analysis was performed for the following risk factors: donor source, sex, malignant disease, disease risk index, conditioning intensity, receipt of rATG/alemtuzumab, GVHD prophylaxis, Grade II-IV GVHD, CMV D/R status, Grade III-IV neutropenia requiring discontinuation of ganciclovir, and CMV viremia. Those with p values <0.2 were included in the multivariate cox regression analysis. The 1-year survival probability was analyzed using log rank test, univariate and multivariate cox regression. Gray's test, univariate, and multivariate cox regression with competing risk were conducted for 1-year NRM. Results: Eighty-four alloSCT recipients with M/F ratio 41/43 and median age 10.8 y (0.4-24.4 y) were analyzed. Eighteen of 84 patients (21%) had grade III/IV neutropenia probably or directly attributed to ganciclovir that was unresponsive to GCSF and required alternative CMV prophylaxis prior to day +100. One-year survival for recipients who continued ganciclovir prophylaxis through day +100 was significantly increased vs. those who did not in univariate (p = 0.0044) and multivariate analyses (p = 0.0463) after adding adjusting factors (conditioning intensity, D/R status, sex, and CMV). Similarly, 1-year NRM was increased in those who discontinued ganciclovir prophylaxis in univariate (p = 0.0083) and multivariate analyses (p = 0.038). Conclusions: One-year survival was significantly decreased and 1-year NRM was significantly increased in patients who had grade III/IV neutropenia probably or directly attributed to ganciclovir that was unresponsive to GCSF and required alternative CMV prophylaxis prior to day +100 and in those who developed CMV viremia. No other risk factors were found to be associated with 1-year survival or 1-year NRM.

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