1761. A Single-Center Experience with Cidofovir for the Treatment of Double-Stranded (ds) DNA Viruses in Hematopoietic Cell Transplant (HCT) Recipients

Abstract

BackgroundCidofovir (CDV), a nucleotide analog antiviral, is active against multiple dsDNA viruses relevant in HCT recipients. Despite a broad spectrum of activity, CDV utility is limited due to nephrotoxicity. We describe our experience with CDV in a large contemporary cohort from a single Institution.MethodsRetrospective review of adult HCT recipients who received CDV for any indication from 2011 to 2017. Initiation and duration of CDV treatment were at physicians’ discretion. CDV exposure and indications, Serum Creatinine (SCr) and outcomes were extracted from medical records and hospital databases.ResultsOf 1,235 HCT recipients, 54 (4.4%) received ≥1 dose of CDV. Stem cell source was peripheral blood in 39 (72%) patients, cord blood in 13 (24%) and marrow in 2(4%); 42 (78%) patients received CD34+ selected HCT. At CDV initiation, 23 (43%) patients had active GvHD and 16 (30%) received systemic steroids. CDV was started a median of 85.5 days (range 14–335) post HCT, given for a median of 3 doses (range 1–13) for a median of 2 weeks (range 1–17). Indications were adenovirus (ADV) infection in 35 patients, CMV in 19, BK virus in 21 and HHV6 in 3 patients. Nineteen (35%) patients had >1 dsDNA virus. Forty-one (76%) patients received CDV (3–5 mg/kg) once weekly, mainly for ADV or CMV, and 13 received CDV (≤1 mg/kg) once to thrice weekly, mostly for BK hemorrhagic cystitis (N = 12). Baseline sCr was mean 0.88 mg/dL (standard deviation [SD] = 0.37) at CDV initiation, mean 1.07 mg/dL at end of treatment (EOT) (SD = 0.57, N = 48, P = 0.004) and mean 1.23 mg/dL at EOT + 2 weeks (SD = 0.72, n = 28, P = 0.027). At EOT, 13 patients (24%) had acute kidney injury (AKI, ≥1.5-fold increase from baseline sCr). Of those, 12 (92%) received concomitant nephrotoxic drugs. AKI was attributed to other etiologies by treating physician in six patients. Of 51 patients with follow-up at EOT, 29 (57%) had clinical response to CDV treatment. Nineteen (35%) patients died ≤ 4 weeks from last CDV dose.Conclusion24% of highly immunocompromised HCT patients experienced AKI following CDV treatment for dsDNA viruses. The co-administration of nephrotoxic medications and the direct effect of infection limit our ability to assess the relative impact of CDV on renal function. Our data underscores the need for safer treatment options for HCT patients with life-threatening infections with dsDNA viruses. Disclosures All authors: No reported disclosures.