Evaluation of the efficacy and tolerability of cidofovir for the treatment of BK virus infection post-allogeneic stem cell transplantation.

Introduction: Haemorrhagic cystitis (HC) is a relatively common complication after allogeneic stem cell transplantation (SCT). Early onset HC is usually caused by the direct effects of chemotherapy or radiotherapy on the bladder mucosa. Late onset HC is most commonly caused by the BK virus, has an incidence of 7%–25%,1 and is associated with significant morbidity. Although debate exists as to the most appropriate treatment, encouraging results have been reported with cidofovir.2 Although its long half-life allows for once-weekly dosing, it is associated with significant nephrotoxicity with a reported incidence of renal dysfunction of 25%–30%.2,3 The aim of this study was to evaluate the realworld efficacy and tolerability of cidofovir in SCT patients with BK virus infection. Methods: Electronic patient records at the Queen Elizabeth Hospital, Birmingham were used to collect data on all allogeneic SCT patients who received at least one dose of cidofovir for the treatment of symptomatic BK virus infection during a 3-year period (Feb 2018–Feb 2021). Key parameters included demographic details, dosing and duration of cidofovir, clinical and virological outcomes and renal function. Data were recorded using Microsoft Excel and descriptive statistical analyses were undertaken. Results: 29 patients (median age: 48, range: 17–72) received cidofovir during the study period (27 male, two female). Six patients had concurrent cytomegalovirus (CMV) infection. The median time from transplant to development of symptomatic BK infection was 36 days (range: 2–820). The median starting dose of cidofovir was 5 mg/kg (range: 1.5–5 mg/kg) and the median number of doses received was 3 (range: 1–13). All patients received concomitant probenecid. In terms of efficacy (based on definitions from Bedi et al.4), a complete response (CR) was achieved in 25 patients (86.2), a partial response (PR) in three patients (10.3%) and clinical failure in one patient (3.5%). For those patients with serial viral load measurements, 89% demonstrated a ≥ 1 log reduction in urinary BK load and 52% demonstrated a ≥ 1 log reduction in blood BK load from baseline. The median baseline creatinine in the cohort was 95 μmol/L (range: 39–214 μmol/L) and at the end of treatment, this had increased to 112 μmol/L (range: 44–327 μmol/L). Nine patients (31%) developed CTCAE grade 2 nephrotoxicity (> 1.5–3 fold increase in creatinine from baseline) and four patients (14%) stopped cidofovir due to nephrotoxicity although in three cases, they had achieved a clinical response prior to cessation. Dose adjustments for baseline renal function5 were observed in 13 patients (45%). Further dose adjustments occurred for 12 patients: seven patients (24%) required a dose reduction due to worsening renal function and five patients (17%) had a dose increase due to improved renal parameters. Discussion and conclusions: IV cidofovir was an effective treatment for BK virus infection after allogeneic SCT. The high response rates seen were comparable to previous work in this area.2 Rates of nephrotoxicity were also similar to literature estimates2,3 and it is noteworthy that 75% of patients in the study were receiving concomitant ciclosporin. The retrospective nature of the study made data collection challenging and future work in this area should focus on a prospective data set. [ABSTRACT FROM AUTHOR]