Neutropenia and renal dysfunction due to intravesical cidofovir for virus‐associated hemorrhagic cystitis after kidney and allogenic hematopoietic stem cell transplantations

Abstract

Virus-associated hemorrhagic cystitis (VAHC) is a common and lifethreatening complication of allogenic hematopoietic stem cell transplantation (allo-HSCT), occurring in 8%-27% of allo-HSCT recipients with severe hematuria. 1 Late onset hemorrhagic cystitis (HC) in the post-engraftment period is associated with an adenovirus (ADV), a BK polyomavirus (BKPyV), or a JC polyomavirus (JCPyV) infection. Hemorrhagic cystitis may cause significant morbidity, prolonged hospital stay, and increased mortality. Risk factors for HC are urotoxic preconditioning regimens (cyclophosphamide, ifosfamide, busulfan and/or total body irradiation [TBI]), use of anti-thymocyte globulin, onset of acute graft versus host disease (GvHD) of grade Ⅱ or above, and the graft source (unrelated donor, cord blood transplantation, and/or human leukocyte antigen [HLA] mismatch). 2According to a recent report on 349 kidney transplant recipients followed up for 3 years, the incidence of ADV urinary infection and disseminated disease was 4.8% and 3.1%, respectively. 3 Therefore, in allo-HSCT and kidney transplant recipients, HC is a major concern.Adenoviremia and BKPyV viremia may cause severe complications such as orchitis, lymphopenia, gastroenteritis, pneumonitis, meningoencephalitis, and HC in allo-HSCT and kidney transplant recipients. In kidney transplant recipients, activities of these viruses may cause HC, leading to allograft loss and mortality.Supportive measures for this condition (eg, bladder irrigation, blood transfusion, and symptom relief) have been the standard of care for many years, and alternate treatments to eliminate viral infections have been attempted (ganciclovir, leflunomide, long-term ciprofloxacin, choreito, hyperbaric oxygen therapy, and intravenous or intravesical cidofovir). Cidofovir, the most commonly used antiviral agent for this condition, acting against ADV and BKPyV, is a cytosine purine analogue that leads to chain termination. 3While intravenous treatment has been effective, 4 myelosuppression and nephrotoxicity are major concerns. Intravenous cidofovir is not a preferred therapy in kidney transplant recipients. Therefore, to reduce nephrotoxicity, intravesical therapy was introduced. 5Based on some reports, the complete response rate was 60%, irrespective of the administration route (intravesical or intravenous). 6 AbstractWe present a patient with virus-associated hemorrhagic cystitis who underwent kidney and allogenic hematopoietic stem cell transplantations (allo-HSCT). Six months post-allo-HSCT, adenovirus hemorrhagic cystitis occurred, which has been in remission after a single dose of intravesical cidofovir. This might cause prolonged neutropenia and nephrotoxicity, suggesting cidofovir absorption in the blood. K E Y W O R D Sallogenic hematopoietic stem cell transplantation, cidofovir, intravesical, kidney transplantation, virus-associated hemorrhagic cystitis

Endovesical instillation of Cidofovir in the treatment of BK polyomavirus hemorrhagic cystitis after allogeneic hematopoietic cell transplantation

“…[15] However, few cases of acute nephrotoxicity have still been reported after cidofovir EV. [18,19] In a pharmacokinetic analysis in 6 adult patients with BKPyV or adenovirus HC, Aitken et al reported that, compared with the reported AUC0−24 for an equivalent IV dose, EV instillation of cidofovir (given at a dose of 2.5 to 5 mg/kg over 30 to 120 min of clamp time) resulted in a 1% to 74% (median 4%) of the corresponding systemic exposure. [18] Thus, although the risk of renal insufficiency seems much lower with EV compared to IV administration, this risk is not completely zero and we recommend to monitor the renal function and to remain cautious, particularly in vulnerable patients with renal comorbidities or nephrotoxic co-medications.…”