title: Cidofovir in the Treatment of BK Virus-Associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation.
abstract: After allogeneic hematopoietic stem cell transplantation (HSCT), BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication. Although supportive measures have been the standard of care for many years, several studies suggested the efficacy of cidofovir. The aim of this study was to assess the safety profile and efficacy of cidofovir. A retrospective study was conducted on all patients treated with cidofovir in our HSCT unit between March 2011 and May 2013. Data for efficacy (partial [PR] or complete response [CR]), prescription (dose, frequency, number of doses, and administration route), and toxicity were collected from published reports and medical files. Renal toxicity was evaluated using creatinine clearance calculated with the Cockcroft and Gault formula. A parallel literature search using PubMed (last search, May 2015) was performed. From March 2011 to June 2013, 27 of 181 patients undergoing allogeneic HSCT in our department received cidofovir for BKV-HC: 24 (88.9%) intravenously, 1 intravesically, and 2 via both routes. Mean dose was 5 mg/kg per administration, for a median of 4 injections (range, 1 to 11), from twice a week to once every 2 weeks. CR was achieved in 22 patients (81.5%), PR in 2, and no response in 2 patients. Eight patients presented renal failure (29.6%): 6 moderate (creatinine clearance < 60 mL/min) and 2 severe (creatinine clearance < 30 mLmin). Mean decrease in creatinine clearance after cidofovir was 27% (35 mL/min; range, 2 to 159). In 3 cases renal insufficiency and hematologic toxicity led to discontinuation of treatment or switch to intravesical instillation. For 3 patients cidofovir dose was reduced because of nephrotoxicity. Thirteen studies have reported on the use of cidofovir for BKV-HC (204 patients) since 2005. Intravenous cidofovir was used for 91.3% of patients, with doses ranging from .5 to 5 mg/kg. The main toxicity reported was renal failure (9% to 50% in 9 studies). Between 60% and 100% of CRs were observed independently of cidofovir dose or administration route. Cidofovir is an effective therapy for BKV-HC but requires very precise renal function management to avoid toxicity. Cidofovir treatment modalities (high dose, intravesical instillation, or low dose [≤1 mg/kg]) needs to be investigated in randomized controlled trials.
authors.affiliation: Clinical Oncology Pharmacy Department, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Philippe
authors.affiliation: Clinical Oncology Pharmacy Department, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre Bénite, France; EMR 3738, University Lyon 1, Lyon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Ranchon
authors.affiliation: Hematology Department, Blood and Marrow Transplantation Unit, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Lila
authors.initials: L
authors.lastname: Gilis
authors.affiliation: Clinical Oncology Pharmacy Department, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Vérane
authors.initials: V
authors.lastname: Schwiertz
authors.affiliation: Clinical Oncology Pharmacy Department, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vantard
authors.affiliation: Infectious Diseases Department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France; INSERM U1052, CRCL, Centre Léon Bérard, Lyon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Ader
authors.affiliation: Hematology Department, Blood and Marrow Transplantation Unit, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Labussiere-Wallet
authors.affiliation: Hematology Department, Blood and Marrow Transplantation Unit, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.affiliation: Hematology Department, Blood and Marrow Transplantation Unit, Hospices Civils de Lyon, Pierre Bénite, France; INSERM U1052, CRCL, Centre Léon Bérard, Lyon, France.
authors.forename: Franck-Emmanuel
authors.initials: FE
authors.lastname: Nicolini
authors.affiliation: Hematology Department, Blood and Marrow Transplantation Unit, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Wattel
authors.affiliation: Hematology Department, Blood and Marrow Transplantation Unit, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Ducastelle-Leprêtre
authors.affiliation: Hematology Department, Blood and Marrow Transplantation Unit, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Barraco
authors.affiliation: Hematology Department, Blood and Marrow Transplantation Unit, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Lebras
authors.affiliation: Hematology Department, Blood and Marrow Transplantation Unit, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.affiliation: Hematology Department, Blood and Marrow Transplantation Unit, Hospices Civils de Lyon, Pierre Bénite, France.
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.affiliation: Clinical Oncology Pharmacy Department, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre Bénite, France; EMR 3738, University Lyon 1, Lyon, France. Electronic address: catherine.rioufol@chu-lyon.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rioufol
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001739:BK Virus / Q000187:drug effects / Q000502:physiology; D000077404:Cidofovir; D003556:Cystitis / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006470:Hemorrhage / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use*; D027601:Polyomavirus Infections / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014412:Tumor Virus Infections / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D019653:Myeloablative Agonists; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir
keywords: BK virus; Cidofovir; Hematopoietic stem cell transplantation; Hemorrhagic cystitis