Summary:
The purpose of this multicenter study was to assess the incidence and the treatment of hemorrhagic cystitis (HC) in 1218 pediatric patients, with a mean age of 10.8 years, who underwent hematopoietic stem cell transplantation (HSCT). In all, 44 patients (3.6%) developed HC a median 23 days after HSCT. The incidence of HC was higher in allogeneic than in autologous HSCT recipients (P=0.0001). Of the 44 patients, 37 (84%) recovered from HC in a median 30 days (range 3–100); the other seven children died while still suffering from HC. Hyperbaric oxygen therapy (HOT) achieved significantly better results than prostaglandin therapy (P=0.02) in the treatment of grade II–III HC. By multivariate analysis, age <96 months and allogeneic HSCT were significantly associated with the occurrence of HC: P=0.008 and 0.013, respectively. After a median follow-up of 5.75 years, the 5-year survival of patients who did or did not develop HC was: 43 vs 52%, P=0.03, respectively. This study indicates that age and type of HSCT are factors predisposing to HC in children given HSCT and demonstrates the promising role of HOT in a conservative approach to HC treatment.
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
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
De Vries CR, Freiha FS . Hemorrhagic cystitis: a review. J Urol 1990; 143: 1–9.
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.
Atkinson K, Biggs J, Noble G et al. Preparative regimens for marrow transplantation containing busulphan are associated with haemorrhagic cystitis and hepatic veno-occlusive disease but a short duration of leucopenia and little oro-pharyngeal mucositis. Bone Marrow Transplant 1987; 2: 385–394.
Russel SJ, Vowels MR, Vale T . Haemorrhagic cyctitis in paediatric bone marrow transplant patients: an association with infective agents, GVHD and prior cyclophosphamide. Bone Marrow Transplant 1994; 13: 533–539.
Kondo M, Kjima S, Kato K, Matsuyama T . Late onset hemorrhagic cystitis after hematopoietic stem cell transplantation in children. Bone Marrow Transplant 1998; 22: 995–998.
Watson NA, Notley RG . Urologic complications of cyclophos-phamide. Br J Urol 1973; 45: 609–612.
Millard RJ . Busulfan-induced haemorrhagic cystitis. Urology 1981; 18: 143–144.
Pode D, Pearlberg S, Steiner D . Busulfan-induced haemorrhagic cystitis. J Urol 1983; 130: 347–348.
Azzi A, Fanci R, Bosi A et al. Monitoring of polyomavirus BK viruria in bone marrow transplantation patients by DNA hybridization assay and by polymerase chain reaction: an approach to assess the relationship between BK viruria and hemorrhagic cystitis. Bone Marrow Transplant 1994; 14: 235–240.
Miyamura K, Takeyama K, Kojima S et al. Hemorrhagic cystitis associated with urinary excretion of adenovirus type 11 following allogeneic bone marrow transplantation. Bone Marrow Transplant 1989; 4: 533–535.
Leung AYH, Suen CKM, Lie AKW et al. Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation. Blood 2001; 98: 1971–1978.
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.
Meisenberg B, Lassiter M, Hussein A et al. Prevention of hemorrhagic cystitis after high-dose alkylating agent chemotherapy and autologous bone marrow support. Bone Marrow Transplant 1994; 14: 287–291.
Turkeri LN, Lum LG, Uberti JP et al. Prevention of hemorrhagic cystitis following allogeneic bone marrow transplant preparative regimens with cyclophosphamide and busulfan. Role of continuous bladder irrigation. J Urol 1995; 153: 637–640.
Shephered JD, Pringle LE, Barnett MJ et al. Mesna versus hyperhydratation for the prevention of cyclophosphamide-induced hemorrhagic cystitis in bone marrow transplantation. J Clin Oncol 1991; 9: 2016–2020.
Hows JM, Mheta A, Ward L et al. Comparison of mesna with forced diuresis to prevent cyclophosphamide induced haemorrhagic cystitis in marrow transplantation. A prospective randomized study. Br J Cancer 1984; 50: 753–756.
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; 7: 1306–1310.
Kranc DM, Kim J, Straus F, Levine LA . Prophylactic and therapeutic carboprost tromethamine bladder irrigation in rats with cyclophosphamide-induced hemorrhagic cystitis. J Urol 1992; 148: 1326.
Gary KJ, Engelmann EH, Johnson EH, Fishman IJ . Evaluation of misoprostol cytoprotection of the bladder with cyclophosphamide (Cytoxan) therapy. J Urol 1986; 136: 497.
Vannucchi AM, Rafanelli D, Longo G et al. Early hemostatic alterations following bone marrow transplantation: a prospective study. Haematologica 1994; 79: 519–525.
Laurence A, Levine MD, Kranc DM . Evaluation of carboprost tromethamine in the treatment of cyclophosphamide-induced hemorrhagic cystitis. Cancer 1990; 66: 242–245.
Bevers RFM, Bakker DJ, Kurth KH . Hyperbaric oxygen treatment for haemorrhagic radiation cystitis. Lancet 1995; 346: 803–805.
Del Pizzo JJ, Chew BH, Jacobs SC, Sklar GN . Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen: long-term follow up. J Urol 1998; 160: 731–733.
Weiss JP, Mattei DM, Neville EC, Hanno PM . Primary treatment of radiation-induced hemorrhagic cystitis with hyperbaric oxygen: 10-year experience. J Urol 1994; 151: 1514–1517.
Hughes AJ, Schwarer AP, Millar IL . Hyperbaric oxygen in the treatment of refractory haemorrhagic cystitis. Bone Marrow Transplant 1998; 22: 585–586.
Shameem IA, Shimabukuro T, Shirataki S et al. Hyperbaric oxygen therapy for control of intractable cyclophosphamide-induced hemorrhagic cystitis. Eur Urol 1992; 22: 263–264.
Hughes WT, Armstrong D, Bodey GP et al. Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Clin Infect Dis 1997; 25: 551–573.
Boeckh M, Gallez-Hawkins GM, Myerson D et al. Plasma polymerase chain reaction for cytomegalovirus DNA after allogeneic marrow transplantation: comparison with poly-merase chain reaction using peripheral blood leukocytes, pp65 antigenemia, and viral culture. Transplantation 1997; 64: 108–113.
Sullivan KM . Acute and chronic graft-versus-host disease in man. Int J Cell Cloning 1986; 4: 42–93.
McDonald GB, Hinds MS, Fisher LD et al. Hepatic veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med 1993; 118: 255–267.
Goodman JL, Winston DJ, Greenfield RA et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 1992; 326: 845–851.
Bearman SI, Appelbaum FR, Buckner CD et al. Regimen related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol 1998; 6: 1562–1568.
Trigg ME, O'Reilly JO, Rumelhart S et al. Prostaglandin E1 bladder instillations to control severe hemorrhagic cystitis. J Urol 1990; 143: 92–94.
Laszlo D, Bosi A, Guidi S et al. Prostaglandin E2 bladder instillation for the treatment of hemorrhagic cystitis after allogeneic bone marrow transplantation. Haematologica 1995; 80: 421–425.
Seber A, Shu XO, Defor T et al. Risk factors for severe hemorrhagic cystitis following BMT. Bone Marrow Transplant 1998; 23: 35–40.
Nevo S, Enger C, Swan V et al. Acute bleeding after allogeneic bone marrow transplantation: association with graft versus host disease and effect on survival. Transplantation 1999; 67: 681–689.
Arthur RR, Shah KV, Baust SJ et al. Association of BK virus with hemorrhagic cystitis in recipients of bone marrow transplants. N Engl J Med 1986; 315: 230–234.
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.
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: 1325–1330.
Shields AF, Hackman RC, Fife KH et al. Adenovirus infections in patients undergoing bone marrow transplantation. N Engl J Med 1985; 312: 529–533.
Carrigan DR . Adenovirus infections in immunocompromised patients. Am J Med 1997; 102: 71–74.
Sencer SF, Haake RJ, Weisdorf . Hemorrhagic cystitis after bone marrow transplantation. Risk factors and complications. Transplantation 1993; 56: 875–897.
Azzi A, Cesaro S, Laszlo D et al. Human polyomavirus BK (BKV) load and haemorrhagic cystitis in bone marrow transplantation patients. J Clin Virol 1999; 14: 78–96.
Paroni R, Del Puppo M, Borghi C et al. Pharmacokinetics of ribavirin and urinary excretion of the major metabolite 1,2,4-triazole-3-carboxamide in normal volunteers. Int J Clin Pharmacol Ther Toxicol 1989; 27: 302–307.
Murphy GF, Wood DP, Mc Roberts JW, Henslee-Downey PJ . Adenovirus-associated hemorrhagic cystitis treated with intravenous ribavirin. J Urol 1993; 149: 565–566.
Cassano WF . Intravenous ribavirin therapy for adenovirus cystitis after allogeneic bone marrow transplantation. Bone Marrow Transplant 1991; 7: 247–248.
Liles WC, Cushing H, Holt S et al. Severe adenovirus nephritis following bone marrow transplantation: successful treatment with intravenous ribavirin. Bone Marrow Transplant 1993; 12: 409–412.
Kitabayashi A, Hirokawa M, Miura AB . Successful vidarabine therapy for adenovirus type 11-associated acute hemorrhagic cystitis after bone marrow transplantation. Bone Marrow Transplant 1994; 14: 853–854.
Chapman C, Flower AJE, Durrant STS . The use of vidarabine in the treatment of human polyomavirus associated acute hemorrhagic cystitis. Bone Marrow Transplant 1991; 7: 481–483.
Kawakami M, Ueda S, Maeda T et al. Vidarabine therapy for virus-associated cystitis after allogeneic bone marrow transplantation. Bone Marrow Transplant 1997; 20: 485–490.
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: 347–350.
Gonzalez-Fraile MI, Canizo C, Caballero D et al. Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis. Transpl Infect Dis 2001; 3: 44–46.
Hoffman JA, Shah AJ, Ross LA, Kapoor N . Adenoviral infections and a prospective trial of cidofovir in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001; 7: 388–394.
Baronciani D, Angelucci E, Erer B et al. Soprapubic cystotomy as treatment for severe hemorrhagic cystitis after bone marrow transplantation. Bone Marrow Transplant 1995; 16: 267–270.
Garderet L, Bittencourt H, Sebe P et al. Cystectomy for severe hemorrhagic cystitis in allogeneic stem cell transplant reci-pients. Transplantation 2000; 70: 1807–1811.
Levine LA, Jarrad DF . Treatment of cyclophosphamide-induced hemorrhagic cystitis with intravesical carborpost tromethamine. J Urol 1993; 149: 719–723.
Grim PS, Gottlieb LJ, Bodie A, Batson E . Hyperbaric oxygen therapy. JAMA 1990; 263: 2216–2220.
Hattori K, Yabe M, Matsumoto M et al. Successful hyperbaric oxygen treatment of life-threatening hemorrhagic cystitis after allogeneic bone marrow transplantation. Bone Marrow Transplant 2001; 27: 1315–1317.
Acknowledgements
The authors thank Lucia Agostini, PhD, and Sandra Volpato, PhD for their help in the data analysis, Judith Kingston, MD, for reviewing the English style of the manuscript, and the nursing staff at each centre caring for the patients.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cesaro, S., Brugiolo, A., Faraci, M. et al. Incidence and treatment of hemorrhagic cystitis in children given hematopoietic stem cell transplantation: a survey from the Italian association of pediatric hematology oncology–bone marrow transplantation group. Bone Marrow Transplant 32, 925–931 (2003). https://doi.org/10.1038/sj.bmt.1704252
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1704252
Keywords
This article is cited by
-
The utility of hyperbaric oxygen therapy in post-transplant cyclophosphamide-induced hemorrhagic cystitis: a case report and review of the literature
Journal of Medical Case Reports (2021)
-
Intravesical application of platelet-rich plasma in patients with persistent haemorrhagic cystitis after hematopoietic stem cell transplantation: a single-centre preliminary experience
International Urology and Nephrology (2019)
-
Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival
Bone Marrow Transplantation (2015)
-
Current Strategies for Prevention and Management of Stem Cell Transplant-Related Urinary Tract and Voiding Dysfunction
Current Bladder Dysfunction Reports (2015)
-
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)