title: Late-onset hemorrhagic cystitis in children after hematopoietic stem cell transplantation for thalassemia and sickle cell anemia: a prospective evaluation of polyoma (BK) virus infection and treatment with cidofovir.
abstract: Little is known about late-onset hemorrhagic cystitis (HC) in children, its relationship to BK virus, and treatment with cidofovir (CDV) following hematopoietic stem cell transplantation (HSCT). We prospectively investigated BK virus reactivation in children who underwent HSCT from a matched related donor for thalassemia or sickle cell anemia following busulfan-cyclophosphamide-based conditioning regimens and analyzed risk factors for development of HC and its treatment with CDV. Grade 2-4 HC occurred in 30 patients with a cumulative incidence of 26% (95% confidence interval [CI] = 18%-34%). The cumulative incidences of BK viruria and viremia were 81% (95% CI = 69%-89%) and 28% (95% CI = 18%-40%), respectively. Multivariate analysis revealed that use of antithymocyte globulin (ATG) (hazard ratio [HR] = 10.5; P = .001), peak BK viruria >100,000 copies/mL (HR = 6.2; P = .004), and grade II-IV acute graft-versus-host disease (HR = 5.3; P = .007) were predictive factors for HC. Nineteen patients with HC were given CDV at 1.5 mg/kg/day 3 times a week, or 5 mg/kg/week. The median duration of therapy was 27 days (range, 21-180 days), and a median of 9 doses were given (range, 6-22). All patients had a complete clinical response (CCR), and 69% had a microbiological response at 4 weeks. Eleven patients with BK virus-related HC receiving supportive care also had CCR. The median duration of HC in these patients was similar to that in patients treated with CDV. None of the patients with HC cleared BK viruria when CCR was achieved. We conclude that late-onset HC is more prevalent in children with sustained high BK viruria who are treated with ATG or who develop graft-versus-host disease. Randomized clinical trials are urgently needed to better define the role of CDV in treating BK virus-related HC.
authors.affiliation: International Center for Transplantation in Thalassemia and Sickle Cell Anemia, Mediterranean Institute of Hematology, Policlinico Tor Vergata, Rome, Italy. j.gaziev@fondazioneime.org
authors.forename: Javid
authors.initials: J
authors.lastname: Gaziev
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Paba
authors.forename: Roberto
authors.initials: R
authors.lastname: Miano
authors.forename: Stefano
authors.initials: S
authors.lastname: Germani
authors.forename: Pietro
authors.initials: P
authors.lastname: Sodani
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Bove
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Marco
authors.initials: M
authors.lastname: Marziali
authors.forename: Cristiano
authors.initials: C
authors.lastname: Gallucci
authors.forename: Antonella
authors.initials: A
authors.lastname: Isgrò
authors.forename: Katia
authors.initials: K
authors.lastname: Paciaroni
authors.forename: Andrea
authors.initials: A
authors.lastname: Roveda
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Simone
authors.forename: Gioia
authors.initials: G
authors.lastname: De Angelis
authors.forename: Cecilia
authors.initials: C
authors.lastname: Alfieri
authors.forename: Guido
authors.initials: G
authors.lastname: Lucarelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000628:therapy; D001739:BK Virus; D002648:Child; D002675:Child, Preschool; D000077404:Cidofovir; D003556:Cystitis / Q000188:drug therapy / Q000209:etiology* / Q000821:virology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006470:Hemorrhage; D006801:Humans; D015994:Incidence; D007223:Infant; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D027601:Polyomavirus Infections / Q000188:drug therapy* / Q000209:etiology; D011446:Prospective Studies; D013789:Thalassemia / Q000150:complications* / Q000628:therapy; D014412:Tumor Virus Infections; D055815:Young Adult
chemical_list: D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir