Treatment of BK virus-associated hemorrhagic cystitis with low-dose intravenous cidofovir in patients undergoing allogeneic hematopoietic cell transplantation
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Background/Aims: BK virus (BKV) has been associated with late-onset hemorrhagiccystitis (HC) in recipients of hematopoietic stem cell transplantation(HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecidprophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia athigh doses. Methods: Allogeneic HSCT recipients with BKV-associated HC are treated with 1mg/kg intravenous cidofovir weekly at our institution. A microbiological responsewas defined as at least a one log reduction in urinary BKV viral load, and a clinicalresponse was defined as improvement in symptoms and stability or reductionin cystitis grade. Results: Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. Aclinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurablemicrobiological response. One patient died of uncontrolled graft-versus-hostdisease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities,which resolved after completion of concomitant calcineurin inhibitor treatment. Conclusions: Weekly intravenous low-dose cidofovir without probenecid appearsto be a safe and effective treatment option for patients with BKV-associated HC.
Abstract
Background/Aims: BK virus (BKV) has been associated with late-onset hemorrhagiccystitis (HC) in recipients of hematopoietic stem cell transplantation(HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecidprophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia athigh doses. Methods: Allogeneic HSCT recipients with BKV-associated HC are treated with 1mg/kg intravenous cidofovir weekly at our institution. A microbiological responsewas defined as at least a one log reduction in urinary BKV viral load, and a clinicalresponse was defined as improvement in symptoms and stability or reductionin cystitis grade. Results: Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. Aclinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurablemicrobiological response. One patient died of uncontrolled graft-versus-hostdisease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities,which resolved after completion of concomitant calcineurin inhibitor treatment. Conclusions: Weekly intravenous low-dose cidofovir without probenecid appearsto be a safe and effective treatment option for patients with BKV-associated HC.
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