Summary:
To establish the most appropriate prophylactic therapy and risk factors for predicting hemorrhagic cystitis (HC) after stem cell transplantation (SCT), we retrospectively analyzed the clinical records of 450 transplant patients treated from 1982 to 2002. In all, 81 patients developed early- and/or late-onset HC (early=29, late=48, both=4). For the incidence of early-onset HC, administration of cyclophosphamide (CY) (p=0.0079, odds ratio (OD)=5.109, 95% confidence interval (CI)=1.533–17.030), busulfan (BU) (p=0.0015, OD=3.336, 95% CI=1.584–7.027), BU+CY (p=0.0001, OD=4.369, 95% CI=2.055–9.292), antithymocyte globulin (p=0.0009, OD=3.368, 95% CI=1.642–6.911), nonradiation (p=0.0163, OD=2.564, 95% CI=0.181–0.841), 2-mercaptoethane sodium sulfonate (Mesna) (p=0.0001, OD=7.519, 95% CI=2.847–19.858), and bladder irrigation (p=0.0001, OD=4.950, 95% CI=2.328–10.523) were risk factors. By Fisher's exact test, the combination of BU and Mesna was a more significant risk factor (P<0.001) than Mesna alone (p=0.008) compared to the administration of neither agent. By multivariate analysis, prophylactic administration of Mesna (p=0.0105, OD=5.301, 95% CI=1.477–19.026) and bladder irrigation (p=0.0001, OD=9.469, 95% CI=3.872–23.156) were significant risk factors of early-onset HC. We conclude that (i) high-dose BU as well as CY is a cause of HC, (ii) protective bladder irrigation has an opposite effect, and (iii) Mesna possibly has a toxic effect on bladder mucosa.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Russell SJ, Vowels MR, Vale T et al. Haemorrhagic cystitis in paediatric bone marrow transplant patients: an association with infective agents, GVHD and prior cyclophosphamide. Bone Marrow Transplant 1994; 13: 533–539.
La Rosa AM, Champlin RE, Mirza N et al. Adenovirus infections in adult recipients of blood and marrow transplants. Clin Infect Dis 2001; 32: 871–876.
Bedi A, Miller CB, Hanson JL et al. Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation. J Clin Oncol 1995; 13: 1103–1109.
Murphy GF, Wood Jr DP, McRoberts JW, Henslee-Downey PJ . Adenovirus-associated hemorrhagic cystitis treated with intravenous ribavirin. J Urol 1993; 149: 565–566.
Arthur RR, Shah KV, Baust SJ et al. Association of BK viruria with hemorrhagic cystitis in recipients of bone marrow transplants. N Engl J Med 1986; 315: 230–234.
Ambinder RF, Burns W, Forman M et al. Hemorrhagic cystitis associated with adenovirus infection in bone marrow transplantation. Arch Intern Med 1986; 146: 1400–1401.
Shepherd JD, Pringle LE, Barnett MJ et al Mesna versus hyperhydration for the prevention of cyclophosphamide-induced hemorrhagic cystitis in bone marrow transplantation. J Clin Oncol 1991; 9: 2016–2020.
Cox PJ . Cyclophosphamide cystitis – identification of acrolein as the causative agent. Biochem Pharmacol 1979; 28: 2045–2049.
Hows JM, Mehta A, Ward L et al. Comparison of Mesna with forced diuresis to prevent cyclophosphamide induced haemorrhagic cystitis in marrow transplantation: a prospective randomised study. Br J Cancer 1984; 50: 753–756.
Thomas AE, Patterson J, Prentice HG et al. Haemorrhagic cystitis in bone marrow transplantation patients: possible increased risk associated with prior busulphan therapy. Bone Marrow Transplant 1987; 4: 347–355.
Ost L, Lonnqvist B, Eriksson L et al. Hemorrhagic cystitis – a manifestation of graft versus host disease? Bone Marrow Transplant 1987; 1: 19–25.
Atkinson K, Biggs JC, Golovsky D et al. Bladder irrigation does not prevent haemorrhagic cystitis in bone marrow transplant recipients. Bone Marrow Transplant 1991; 7: 351–354.
Brugieres L, Hartmann O, Travagli JP et al. Hemorrhagic cystitis following high-dose chemotherapy and bone marrow transplantation in children with malignancies: incidence, clinical course, and outcome. J Clin Oncol 1989; 7: 194–199.
Sencer SF, Haake RJ, Weisdorf DJ . Hemorrhagic cystitis after bone marrow transplantation. Risk factors and complications. Transplantation 1993; 56: 875–879.
Seber A, Shu XO, Defor T et al. Risk factors for severe hemorrhagic cystitis following BMT. Bone Marrow Transplant 1999; 23: 35–40.
Morgan M, Dodds A, Atkinson K et al. The toxicity of busulphan and cyclophosphamide as the preparative regimen for bone marrow transplantation. Br J Haematol 1991; 77: 529–534.
Ringden O, Labopin M, Tura S et al. A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 1996; 93: 637–645.
Vose JM, Reed EC, Pippert GC et al. Mesna compared with continuous bladder irrigation as uroprotection during high-dose chemotherapy and transplantation: a randomized trial. J Clin Oncol 1993; 11: 1306–1310.
Moriyama Y, Koike T, Shibata A . Hemorrhagic cystitis after conditioning for bone marrow transplantation and its prophylaxis. Jpn J Clin Oncol 1984; 14: 531–536.
Acknowledgements
We are grateful to Mr Hiroki Akiyama (Meiji Seika Kaisha, Ltd) for performing the statistical analysis of the data.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tsuboi, K., Kishi, K., Ohmachi, K. et al. Multivariate analysis of risk factors for hemorrhagic cystitis after hematopoietic stem cell transplantation. Bone Marrow Transplant 32, 903–907 (2003). https://doi.org/10.1038/sj.bmt.1704240
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1704240
Keywords
This article is cited by
-
Predictors of kidney complications and analysis of hypertension in children with allogeneic hematopoietic stem cell transplantation
Pediatric Nephrology (2023)
-
CMV infection is a risk factor for hemorrhagic cystitis after hematopoietic stem cell transplantation
Annals of Hematology (2023)
-
The use of hyperbaric oxygen therapy in the treatment of hemorrhagic cystitis after allogeneic stem cell transplantation from an unrelated donor
International Journal of Hematology (2015)
-
Fulminating Hemorrhagic Cystitis: New Trends from Etiology to Treatment
Current Bladder Dysfunction Reports (2015)
-
Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation
Journal of Hematology & Oncology (2013)