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

Javid Gaziev, Pierpaolo Paba, Roberto Miano, Stefano Germani, Pietro Sodani, Pierluigi Bove, Carlo Federico Perno, Marco Marziali, Cristiano Gallucci, Antonella Isgrò, Katia Paciaroni, Andrea Roveda, Maria Domenica Simone, Gioia De Angelis, Cecilia Alfieri, Guido Lucarelli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)662-671
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume16
Issue number5
DOIs
Publication statusPublished - May 2010

Keywords

  • BK virus
  • Cidofovir
  • Hemoglobinopathies
  • Hemorrhagic cystitis
  • Stem cell transplantation

ASJC Scopus subject areas

  • Transplantation
  • Hematology

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    Gaziev, J., Paba, P., Miano, R., Germani, S., Sodani, P., Bove, P., Perno, C. F., Marziali, M., Gallucci, C., Isgrò, A., Paciaroni, K., Roveda, A., Simone, M. D., De Angelis, G., Alfieri, C., & Lucarelli, G. (2010). 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. Biology of Blood and Marrow Transplantation, 16(5), 662-671. https://doi.org/10.1016/j.bbmt.2009.12.009