Korean J Hematol.  2007 Jun;42(2):114-121. 10.5045/kjh.2007.42.2.114.

Viruria in Adult Hemorrhagic Cystitis Patients Following Allogeneic Hematopoietic Stem Cell Transplantation and Implication of Antiviral Treatment

• Kim SY
• Lee JW
• Lee KM
• Cho BS
• Eom KS
• Kim YJ
• Lee S
• Min CK
• Kim HJ
• Cho SG
• Kim DW
• Min WS
• Kim CC

• KMID: 2083508
• DOI: http://doi.org/10.5045/kjh.2007.42.2.114

Abstract

BACKGROUND: Viruria is frequently detected in patients who have had hemorrhagic cystitis (HC) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Urinary viruses, especially BK virus, have been suggested as a cause of HC following allo-HSCT, therefore antiviral therapy is emerging as a therapeutic approach for its treatment.
METHODS
Adult HC patients who underwent allo-HSCT from January 2005 to March 2006 at a single institution were enrolled. We performed a PCR-based assay for BK virus, JC virus, and CMV virus in urine obtained from the patients to determine the incidence of viruria, and the type of virus detected in the urine, and the effect of treatment with cidofovir on HC.
RESULTS
Of 155 patients that received allo-HSCT during the study period, 22 (14.2%) experienced HC. A viral study of urine obtained from 19 of these 22 patients revealed that 16 (84.2%) had viruria. Eleven patients had grade III-IV HC, 5 of which were treated with intravenous cidofovir. Three of the HC patients who underwent treatment responded to cidofovir, 1 had no response, and 1 had a complete response followed by recurrence.
CONCLUSION
Most adult HC patients (84.2%) had viruria following allo-HSCT, however the response rate to antiviral therapy with intravenous cidofovir for the treatment of high grade HC (grade III-IV) was 80%. Therefore, antiviral therapy should be considered if high grade HC does not respond to hyperhydration and transfusional support.

Keyword

Viruria; Cystitis; Hematopoietic stem cell transplantation; Cidofovir

MeSH Terms

Adult*
BK Virus
Cystitis*
Hematopoietic Stem Cell Transplantation*
Hematopoietic Stem Cells*
Humans
Incidence
JC Virus
Recurrence

Figure

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  Fig. 1 Treatment outcome of hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Abbreviations: IVH, intravenous hyperhydration; CR, complete response; NR, no response; CBI, continuous bladder irrigation with water; rhGM-CSF, intravesical recombinant human granulocyte-macrophage colony-stimulating factor instillation; AI, intravesical alum irrigation; CDV, intravenous cidofovir; TAE, transarterial embolization.

Reference

1). Gorczynska E., Turkiewicz D., Rybka K, et al. Incidence, clinical outcome, and management of virus-induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2005. 11:797–804.

2). El-Zimaity M., Saliba R., Chan K, et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters. Blood. 2004. 103:4674–80.

3). Yamamoto R., Kusumi E., Kami M, et al. Late hemorrhagic cystitis after reduced-intensity hematopoietic stem cell transplantation (RIST). Bone Marrow Transplant. 2003. 32:1089–95.

4). Leung AY., Yuen KY., Kwong YL. Polyoma BK virus and haemorrhagic cystitis in haematopoietic stem cell transplantation: a changing paradigm. Bone Marrow Transplant. 2005. 36:929–37.

5). Palandri F., Bonifazi F., Rossi C, et al. Successful treatment of severe hemorrhagic cystitis with selective vesical artery embolization. Bone Marrow Transplant. 2005. 35:529–30.

6). Gine E., Rovira M., Real I, et al. Successful treatment of severe hemorrhagic cystitis after hemopoietic cell transplantation by selective embolization of the vesical arteries. Bone Marrow Transplant. 2003. 31:923–5.

7). Dorticos E., Pavon V., Jaime JC, et al. Successful application of epidermal growth factor for treatment of hemorrhagic cystitis after bone marrow transplantation. Bone Marrow Transplant. 2003. 31:615–6.

8). Arthur RR., Shah KV., Baust SJ., Santos GW., Saral R. Association of BK viruria with hemorrhagic cystitis in recipients of bone marrow transplants. N Engl J Med. 1986. 315:230–4.

9). Arthur RR., Shah KV., Charache P., Saral R. BK and JC virus infections in recipients of bone marrow transplants. J Infect Dis. 1988. 158:563–9.

10). Apperley JF., Rice SJ., Bishop JA, et al. Late-onset hemorrhagic cystitis associated with urinary excretion of polyomaviruses after bone marrow transplantation. Transplantation. 1987. 43:108–12.

11). Bielorai B., Shulman LM., Rechavi G., Toren A. CMV reactivation induced BK virus-associated late onset hemorrhagic cystitis after peripheral blood stem cell transplantation. Bone Marrow Transplant. 2001. 28:613–4.

12). Akiyama H., Kurosu T., Sakashita C, et al. Adenovirus is a key pathogen in hemorrhagic cystitis associated with bone marrow transplantation. Clin Infect Dis. 2001. 32:1325–30.

13). Fedele CG., Ciardi M., Delia S., Echevarria JM., Tenorio A. Multiplex polymerase chain reaction for the simultaneous detection and typing of polyomavirus JC, BK and SV40 DNA in clinical samples. J Virol Methods. 1999. 82:137–44.

14). Yamamoto AY., Mussi-Pinhata MM., Pinto PC., Figueiredo LT., Jorge SM. Usefulness of blood and urine samples collected on filter paper in detecting cytomegalovirus by the polymerase chain reaction technique. J Virol Methods. 2001. 97:159–64.

15). Held TK., Biel SS., Nitsche A, et al. Treatment of BK virus-associated hemorrhagic cystitis and simultaneous CMV reactivation with cidofovir. Bone Marrow Transplant. 2000. 26:347–50.

16). Leung AY., Suen CK., Lie AK., Liang RH., Yuen KY., Kwong YL. Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation. Blood. 2001. 98:1971–8.

17). Lee GW., Lee JH., Choi SJ, et al. Hemorrhagic cystitis following allogeneic hematopoietic cell transplantation. J Korean Med Sci. 2003. 18:191–5.

18). Heath JA., Mishra S., Mitchell S., Waters KD., Tiedemann K. Estrogen as treatment of hemorrhagic cystitis in children and adolescents undergoing bone marrow transplantation. Bone Marrow Transplant. 2006. 37:523–6.

19). Ordemann R., Naumann R., Geissler G., Bornhauser M., Schuler U., Ehninger G. Encouraging results in the treatment of haemorrhagic cystitis with estrogen - report of 10 cases and review of the literature. Bone Marrow Transplant. 2000. 25:981–5.

20). Alrabiah FA., Sacks SL. New antiherpesvirus agents. Their targets and therapeutic potential. Drugs. 1996. 52:17–32.

21). Lea AP., Bryson HM. Cidofovir. Drugs. 1996. 52:225–30.

22). Gonzalez-Fraile MI., Canizo C., Caballero D, et al. Cidofovir treatment of human polyomavirus- associated acute haemorrhagic cystitis. Transpl Infect Dis. 2001. 3:44–6.