Skip to main content

Advertisement

SpringerLink
Log in

Incidence and risk factors of late-onset hemorrhagic cystitis after single umbilical cord blood transplantation with myeloablative conditioning regimen

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Objective

To explore the incidence and risk factors of late-onset hemorrhagic cystitis (LOHC) in patients undergoing single umbilical cord blood transplantation for hematological malignancies.

Methods

Clinical data from 234 patients who consecutively underwent single UCBT using a myeloablative conditioning regimen without antithymocyte globulin in our center were retrospectively analyzed.

Results

In total, 64 (27.4%) patients developed LOHC with a median onset time of 40.5 (range 8–154) days, and 15 (6.4%) patients gradually developed grade III–IV LOHC. The incidence of LOHC was marginally higher in adults (31.0%) than in children (23.7%) (p = 0.248). HLA matching ≤ 6/8 (HR = 2.624, 95% CI 1.112–6.191, p = 0.028) was an independent risk factor for LOHC. The overall survival of LOHC patients (59.8%, 95% CI 61.7–85.5%) was significantly lower than that of patients without LOHC (86.8%, 95% CI 79.6–91.6%) at 130 days post transplantation (p = 0.036).

Conclusion

Patients with less well-matched grafts have a higher incidence of LOHC. Inherent deficiencies in immunity in the context of HLA disparity and more intense pharmacologic immunosuppression after severe acute graft-versus-host disease may contribute to viral activation. Prevention and treatment of LOHC have the potential to prolong long-term survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Fu HX, Xu LP, Liu DH, Liu KY, Chen H, Han W, et al. Higher proportions of peripheral CD19+CD5+ B cells predict the effect of corticosteroid in patients with late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Chin Med J. 2011;124:1517–23.

    PubMed  Google Scholar 

  2. Asano Y, Kanda Y, Ogawa N, Sakata-Yanagimoto M, Nakagawa M, Kawazu M, et al. Male predominance among Japanese adult patients with late-onset hemorrhagic cystitis after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2003;32:1175–9.

    Article  CAS  Google Scholar 

  3. Han TT, Xu LP, Liu DH, Liu KY, Fu HX, Zhao XY, et al. Cytomegalovirus is a potential risk factor for late-onset hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2014;89:55–61.

    Article  CAS  Google Scholar 

  4. Gaziev J, Paba P, Miano R, Germani S, Sodani P, Bove P, et al. 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. Biol Blood Marrow Transplant. 2010;16:662–71.

    Article  CAS  Google Scholar 

  5. Fu H, Xu L, Liu D, Zhang X, Liu K, Chen H, et al. Late-onset hemorrhagic cystitis after haploidentical hematopoietic stem cell transplantation in patients with advanced leukemia: differences in ATG dosage are key. Int J Hematol. 2013;98:89–95.

    Article  Google Scholar 

  6. Ruggeri A, Roth-Guepin G, Battipaglia G, Mamez AC, Malard F, Gomez A, et al. Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients. Transpl Infect Dis. 2015;17:822–30.

    Article  CAS  Google Scholar 

  7. El-Zimaity M, Saliba R, Chan K, Shahjahan M, Carrasco A, Khorshid O, et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters. Blood. 2004;103:4674–80.

    Article  CAS  Google Scholar 

  8. Tomonari A, Takahashi S, Ooi J, Fukuno K, Takasugi K, Tsukada N, et al. Hemorrhagic cystitis in adults after unrelated cord blood transplantation: a single-institution experience in Japan. Int J Hematol. 2006;84:268–71.

    Article  Google Scholar 

  9. Gilis L, Morisset S, Billaud G, Ducastelle-Leprêtre S, Labussière-Wallet H, Nicolini FE, et al. High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2014;49:664–70.

    Article  CAS  Google Scholar 

  10. Uhm J, Hamad N, Michelis FV, Shanavas M, Kuruvilla J, Gupta V, et al. The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD. Bone Marrow Transplant. 2014;49:1528–34.

    Article  CAS  Google Scholar 

  11. Lunde LE, Dasaraju S, Cao Q, Cohn CS, Reding M, Bejanyan N, et al. Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival. Bone Marrow Transplant. 2015;50:1432–7.

    Article  CAS  Google Scholar 

  12. Arai Y, Maeda T, Sugiura H, Matsui H, Jo T, Ueda T, et al. Risk factors for and prognosis of hemorrhagic cystitis after allogeneic stem cell transplantation: retrospective analysis in a single institution. Hematology. 2012;17:207–14.

    Article  CAS  Google Scholar 

  13. Kloos RQ, Boelens JJ, de Jong TP, Versluys B, Bierings M. Hemorrhagic cystitis in a cohort of pediatric transplantations: incidence, treatment, outcome, and risk factors. Biol Blood Marrow Transplant. 2013;19:1263–6.

    Article  Google Scholar 

  14. Kondo M, Kojima S, Kato K, Matsuyama T. Late-onset hemorrhagic cystitis after hematopoietic stem cell transplantation in children. Bone Marrow Transplant. 1998;22:995–8.

    Article  CAS  Google Scholar 

  15. Shakiba E, Yaghobi R, Ramzi M. Prevalence of viral infections and hemorrhagic cystitis in hematopoietic stem cell transplant recipients. Exp Clin Transplant. 2011;9:405–12.

    PubMed  Google Scholar 

  16. Silva Lde P, Patah PA, Saliba RM, Szewczyk NA, Gilman L, Neumann J, et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type. Haematologica. 2010;95:1183–90.

    Article  Google Scholar 

  17. Visintini C, Venturini M, Palese A. Haemorrhagic cystitis, preventive and treatment interventions in patients undergoing haematopoietic stem cell transplantation: a scoping review. Eur J Oncol Nurs. 2019;42:50–62.

    Article  Google Scholar 

  18. Cesaro S, Dalianis T, Hanssen Rinaldo C, Koskenvuo M, Pegoraro A, Einsele H, et al. ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients. J Antimicrob Chemother. 2018;73:12–21.

    Article  CAS  Google Scholar 

  19. Mori Y, Miyamoto T, Kato K, Kamezaki K, Kuriyama T, Oku S, et al. Different risk factors related to adenovirus- or BK virus-associated hemorrhagic cystitis following allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2012;18:458–65.

    Article  Google Scholar 

  20. Servais S, Lengline E, Porcher R, Carmagnat M, de Peffault LR, Robin M, et al. Long-term immune reconstitution and infection burden after mismatched hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20:507–17.

    Article  Google Scholar 

  21. Zao JH, Schechter T, Liu WJ, Gerges S, Gassas A, Egeler RM, et al. Performance of busulfan dosing guidelines for pediatric hematopoietic stem cell transplant conditioning. Biol Blood Marrow Transplant. 2015;21:1471–8.

    Article  CAS  Google Scholar 

  22. Sun Z, Liu H, Luo C, Geng L, Zheng C, Tang B, et al. Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: a retrospective (development) and a prospective (validation) study. Int J Cancer. 2018;143:699–708.

    Article  CAS  Google Scholar 

  23. Mo XD, Zhang XH, Xu LP, Wang Y, Yan CH, Chen H, et al. Treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: the role of corticosteroids. Ann Hematol. 2018;97:1209–17.

    Article  Google Scholar 

  24. Bedi A, Miller CB, Hanson JL, Goodman S, Ambinder RF, Charache P, et al. Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation. J Clin Oncol. 1995;13:1103–9.

    Article  CAS  Google Scholar 

  25. Droller MJ, Saral R, Santos G. Prevention of cyclophosphamide-induced hemorrhagic cystitis. Urology. 1982;20:256–8.

    Article  CAS  Google Scholar 

  26. Lee YH, Lim YJ, Kim JY, Kim YD, Lee SW. Pre-engraftment syndrome in hematopoietic stem cell transplantation. J Korean Med Sci. 2008;23:98–103.

    Article  Google Scholar 

  27. Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, Bunworasate U, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016;22:4–10.

    Article  Google Scholar 

  28. Ramirez P, Brunstein CG, Miller B, Defor T, Weisdorf D. Delayed platelet recovery after allogeneic transplantation: a predictor of increased treatment-related mortality and poorer survival. Bone Marrow Transplant. 2011;46:981–6.

    Article  CAS  Google Scholar 

  29. Bejanyan N, Brunstein CG, Cao Q, Lazaryan A, Luo X, Curtsinger J, et al. Delayed immune reconstitution after allogeneic transplantation increases the risks of mortality and chronic GVHD. Blood Adv. 2018;2:909–22.

    Article  CAS  Google Scholar 

  30. Copelan OR, Sanikommu SR, Trivedi JS, Butler C, Ai J, Ragon BK, et al. Higher incidence of hemorrhagic cystitis following haploidentical related donor transplantation compared with matched related donor transplantation. Biol Blood Marrow Transplant. 2019;25:785–90.

    Article  Google Scholar 

  31. Hayashi H, Volt F, Sanz J, Petersen E, Dhedin N, Hough R, et al. Myeloablative unrelated cord blood transplantation in adolescents and young adults with acute leukemia. Biol Blood Marrow Transplant. 2019;25:2438–46.

    Article  CAS  Google Scholar 

  32. Schneidewind L, Neumann T, Knoll F, Zimmermann K, Smola S, Schmidt CA, et al. Are the polyomaviruses BK and JC associated with opportunistic infections, graft-versus-host disease, or worse outcomes in adult patients receiving their first allogeneic stem cell transplantation with low-dose alemtuzumab? Acta Haematol. 2017;138:3–9.

    Article  CAS  Google Scholar 

  33. Atilla E, Yalciner M, Atilla PA, Ates C, Bozdag SC, Yuksel MK, et al. Is cytomegalovirus a risk factor for haemorrhagic cystitis in allogeneic haematopoietic stem cell transplantation recipients? Antivir Ther. 2018;23:647–53.

    Article  CAS  Google Scholar 

  34. Yanagisawa T, Saito S, Katsuyama Y, Hirabayashi K, Shigemura T, Tanaka M, et al. Successful induction of therapeutic urinary concentration by intravenous ganciclovir and oral valganciclovir with remission of adenoviral hemorrhagic cystitis after cord blood transplantation. Pediatr Transplant. 2018;22:e13241.

    Article  Google Scholar 

  35. Nakazawa Y, Saito S, Yanagisawa R, Suzuki T, Ito T, Ishida F, et al. Recipient seropositivity for adenovirus type 11 (AdV11) is a highly predictive factor for the development of AdV11-induced hemorrhagic cystitis after allogeneic hematopoietic SCT. Bone Marrow Transplant. 2013;48:737–9.

    Article  CAS  Google Scholar 

  36. Onda Y, Kanda J, Hanaoka N, Watanabe M, Arai Y, Hishizawa M, et al. Possible nosocomial transmission of virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Ann Hematol. 2021;100:753–61.

    Article  CAS  Google Scholar 

  37. Riachy E, Krauel L, Rich BS, McEvoy MP, Honeyman JN, Boulad F, et al. Risk factors and predictors of severity score and complications of pediatric hemorrhagic cystitis. J Urol. 2014;191:186–92.

    Article  Google Scholar 

  38. Laskin BL, Denburg M, Furth S, Diorio D, Goebel J, Davies SM, et al. BK viremia precedes hemorrhagic cystitis in children undergoing allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013;19:1175–82.

    Article  Google Scholar 

  39. Schietinger A, Greenberg PD. Tolerance and exhaustion: defining mechanisms of T cell dysfunction. Trends Immunol. 2014;35:51–60.

    Article  CAS  Google Scholar 

  40. Kato M, Kurata M, Kanda J, Kato K, Tomizawa D, Kudo K, et al. Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia. Bone Marrow Transplant. 2019;54:68–75.

    Article  Google Scholar 

Download references

Acknowledgements

The study was supported by a grant from program of Key Research and Development Plan in Anhui in 2017, China (1704a0802149) and the Fundamental Research Funds for the Central Universities (WK9110000001).

Author information

Authors and Affiliations

  1. Department of Hematology of Anhui Provincial Hospital, Anhui Medical University, Hefei, China

    Huimin Jiang & Huilan Liu

  2. Department of Hematology, the First Affiliated Hospital of University of Science and Technology of China, No.17, Lujiang Road, Hefei, Anhui, China

    Liangquan Geng, Xiang Wan, Kaidi Song, Juan Tong, Xiaoyu Zhu, Baolin Tang, Wen Yao, Xuhan Zhang, Guangyu Sun, Lei Zhang, Zimin Sun & Huilan Liu

  3. Blood and Cell Therapy Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

    Xiaoyu Zhu, Zimin Sun & Huilan Liu

Authors
  1. Huimin Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liangquan Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiang Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kaidi Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juan Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaoyu Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Baolin Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wen Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xuhan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Guangyu Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Zimin Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Huilan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HL, LG, JT, XZ and ZS designed this retrospective study and revised the manuscript of draft. HJ performed the data collection and analyze and wrote the manuscript. XW, KS, GS, and LZ contributed to primary data collection and extraction. BT, WY and XZ completed the statistical analysis and prepared Tables and Figures. All authors have read and approve the final version of this manuscript.

Corresponding author

Correspondence to Huilan Liu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The work was done at the Department of Hematology, Anhui Provincial Hospital, Hefei, China.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, H., Geng, L., Wan, X. et al. Incidence and risk factors of late-onset hemorrhagic cystitis after single umbilical cord blood transplantation with myeloablative conditioning regimen. Int J Hematol 114, 381–389 (2021). https://doi.org/10.1007/s12185-021-03168-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-021-03168-w

Keywords

Search

Navigation