Summary
Background
Hemorrhagic cystitis (HC) is an important adverse event experienced after hematopoietic
stem cell transplantation (HSCT). Severe HC could lead to significant morbidity, prolonged
hospitalization with increased health-care costs, and may cause considerable mortality.
Objectives
In order to investigate the influence of different contributing factors other than
BK viruria on HC occurrence in a homogenous population, we retrospectively analyzed
the potential risk factors.
Study design
We conducted a retrospective study among 200 patients (median age 12.4 years, IQR:
7.9–16.1) with acute leukemia who received peripheral blood allogenic HSCT after radiation-free
myeloablative conditioning regimen, in pediatric cell therapy department of Research
Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Tehran, Iran, between
December 2014 and December 2021. Associations between risk factors and outcomes were
examined by univariable and multivariable logistic regression models.
Results
A total of 46 patients (23%) had developed HC during the study period. The median
onset of HC was 29 (IQR: 24–37) days post-transplant, and it persisted for a median
of 33 (7–270) days. The incidence of HC in our patients was estimated to be 3 in 1000
cases (95% CI: 2–4). The results of multivariable logistic model shows that the chance
of HC in T-cell acute lymphoblastic leukemia (ALL) compared to B-cell All is nearly
five times more (OR = 4.88; 95%CI: (1.51–15.78), P = 0.008). The incidence of HC in
patients who underwent HSCT from haploidentical donors was significantly higher than
full matched donors (P < 0.001). Undergoing transplant from a matched unrelated and
haploidentical donor both augment the chance of HC in about six times more than matched
related donors (OR = 6.36; 95%CI: (1.58–25.49), P = 0.009 and OR = 5.7; 95%CI: (1.83–17.75),
P = 0.003, respectively). In patients who developed HC compared to non-HC group, overall
survival was much worse (P < 0.001).
Discussion
Most studies have failed to demonstrate any relationship between late-onset HC and
the dose of cyclophosphamide. In our study, although the dose of cyclophosphamide
was similar in HSCT from MRD and MUD, the hazard of HC incidence was significantly
higher in the latter group. This could be accredited to ATG, as in patients in the
MRD group who had not received any ATG, the incidence of HC was much lower than the
patients who had underwent HSCT from MUD or haploidentical donor group.
Conclusions
Graphical Abstract
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Pediatric UrologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Acute bleeding after bone marrow transplantation (BMT)—incidence and effect on survival. A quantitative analysis in 1,402 patients.Blood. 1998 Feb 15; 91: 1469-1477
- Risk factors for severe hemorrhagic cystitis following BMT.Bone Marrow Transplant. 1999; 23: 35
- High incidence of adeno- and polyomavirus-induced hemorrhagic cystitis in bone marrow allotransplantation for hematological malignancy following T cell depletion and cyclosporine.Bone Marrow Transplant. 1998 Nov; 22: 889-893
- Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters.Blood. 2004 Jun 15; 103: 4674-4680
- Polyoma BK virus and haemorrhagic cystitis in haematopoietic stem cell transplantation: a changing paradigm.Bone Marrow Transplant. 2005; 36 (–937Return to ref 3 in article): 929
- Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival.Bone Marrow Transplant. 2015; 50: 1432-1437
- Full myeloablative conditioning and an unrelated HLA mismatched donor increase the risk for BK virus-positive hemorrhagic cystitis in allogeneic hematopoetic stem cell transplanted patients.Anticancer Res. 2011; 31: 939-944
- BK and JC virus infections in recipients of bone marrow transplants.J Infect Dis. 1988; 158: 563-569
- Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation.Blood. 2001; 98 (–1978): 1971
- Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type.Haematologica. 2010 Jul; 95: 1183
- Hemorrhagic cystitis after bone-marrow transplantation - risk-factors and complications.Transplantation. 1993; 56: 875-879
- 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
- Prevention of cyclophosphamide- induced hemorrhagic cystitis.Urology. 1982; 20: 256-258
- Opportunistic posttransplantation virus infections in renal transplant recipients.Transplant Proc. 2011; 43: 3715-3719
- BK-viruria and haemorrhagic cystitis are more frequent in allogeneic haematopoietic stem cell transplant patients receiving full conditioning and unrelated-HLA-mismatched grafts.Bone Marrow Transplant. 2008; 41: 737-742
- BK virus-associated fatal renal failure following late-onset hemorrhagic cystitis in an unrelated bone marrow transplantation.Pediatr Hematol Oncol. 2002; 19: 255-261
- Cyclophosphamide cystitis—identification of acrolein as the causative agent.Biochem Pharmacol. 1979; 28: 2045-2049
- Urinary excretion and pharmacokinetics of acrolein and its parent drug cyclophosphamide in bone marrow transplant patients.Bone Marrow Transplant. 1998; 22: 485-490
- Hemorrhagic cystitis after allogeneic bone marrow transplantation in children: clinical characteristics and outcome.Biol Blood Marrow Transplant. 2003 Nov 1; 9: 698-705
- Immune reconstitution after haematopoietic transplantation with two different doses of pre-graft antithymocyte globulin.Bone Marrow Transplant. 2002; 30: 421
- 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 Jul; 98: 89-95
- Hemorrhagic cystitis following hematopoietic stem cell transplantation: incidence, risk factors and association with CMV reactivation and graft-versus-host disease.Chinese Med J. 2007 Oct 5; 120: 1666-1671
- The polyomavirus puzzle: is host immune response beneficial in controlling BK virus after adult hematopoietic cell transplantation?.Transpl Infect Dis. 2014; 16: 521-531https://doi.org/10.1111/tid.12233
- Haemorrhagic cystitis: incidence and risk factors in a transplant population using hyperhydration.Bone Marrow Transplant. 1999 Apr; 23: 797-801
- Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation.J Clin Microbiol. 2004 Nov; 42: 5394-5396
- 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 May 1; 16: 662-671
Article info
Publication history
Published online: November 10, 2022
Accepted:
November 6,
2022
Received in revised form:
October 19,
2022
Received:
July 24,
2022
Identification
Copyright
© 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
