A survey on the practices and the management of hemorrhagic cystitis in patients who undergo allogeneic hematopoietic stem cell transplantation, on behalf of the Infectious Diseases Working Party of EBMT.

BK viras is a human polyoma viras. It is acquired in early childhood and remains life-long latent in the genitourinary system. BK virus replication is more common in receiving immunosuppressive therapy receiving patients and transplant patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic stem cell transplantation. Hemorrhagic cystitis is a serious complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause morbidity and long stay in the hospital. Diagnosis is more frequently determined by the presence of BK virus DNA detected with quantitative or real-time PCR testing in serum or plasma and less often in urine. The reduction of immunosuppression is effective in the treatment of BK virus infection. There are also several agents with anti-BK virus activity. Cidofovir is an active agent against a variety of DNA viruses including poliomyoma viruses and it is a cytosine nucleotide analogue. Intravenous immunoglobulin IgG (IVIG) also includes antibodies against BK and JC (John Cunningham) viruses. Hereby, we report three cases of hemorrhagic cystitis. Hemorrhagic cystitis developed in all these three cases of allogeneic stem cell transplantation due to acute myeloid leukemia (AML). BK virus were detected as the cause of hemorrhagic cystitis in these patients. Irrigation of the bladder was performed. Then levofloxacin 1 x750 mg intravenous and IVIG 0.5 gr/kg were started. But the hematuria did not decreased. In the first case, treatment with leflunomide was started, but patient died due to refractory AML and severe graft-versus-host disease after 4th day of leflunamide and levofloxacin treatments. Cidofovir treatment and the reduction of immunosuppressive treatment decreased the BK virus load and resulted symptomatic improvement in the second case. Initiation of cidofovir was planned in the third case. Administration of cidofovir together with the reduction of immunosuppression in the treatment of hemorrhagic cystitis associated with BK virus in allogeneic stem cell transplant recipients could be a good option.

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

Hemorrhagic Cystitis in Patients Undergoing Allogeneic Hematopoietic Cell Transplant with Post Transplant Cyclophosphamide As GvHD Prophylaxis

Fanconi anemia (FA) is an inherited disorder characterized by congenital malformations, bone marrow failure, and malignancies. Hematopoietic cell transplant (HCT) is the only proven cure for the hematological complications. FA patients have increased chromosomal instability and aberrant deoxyribonucleic acid repair and thus can only tolerate low doses of chemotherapy or radiation as part of conditioning prior to HCT. Yet, they are still prone to severe regimen related toxicities including hemorrhagic cystitis (HC) from cyclophosphamide (CY). As CYP2B6 is a primary enzyme responsible for the catalyzation of the prodrug form of CY, understanding the association between CYP2B6 genetic variants and HC in FA patients may predict which patients will be more susceptible to developing HC. A descriptive genetic association study was performed to identify genetic variants associated with HC in patients with FA who underwent HCT between 1999 and 2017. All patients received a CY-based preparative regimen and had pretransplant recipient deoxyribonucleic acid available for genomic analysis. Forty FA pediatric patients were eligible for this analysis. They had received HCT from matched sibling donors (n = 6) or alternative donors (n = 34) for marrow failure (n = 38) or myelodysplastic syndrome (n = 2). The incidence of HC was 32.5% which occurred at a median of 32 days (range 20-180) after HCT. 9 patients had a concomitant viral infection (BK virus, n = 8 both adenovirus and BK virus, n = 1). No genetic variants were significantly associated with HC. The top variants were rs2279343 (g.23060A > G), and rs2279344 (g.23280G > A) in the CYP2B6 gene. The incidence of HC among FA patients with the rs2279343 variant was 42% (CI 22%-62%) compared to 20% (CI 0%-40%) among those without the variant (P = .19). The incidence of HC among patients with the variant in rs2279344 was 40% (CI 22%-58%) compared to 10% (CI 0%-28%) among those without (P = .11). No variants in our analysis were statistically associated with HC. The data suggest that CYP2B6 variants may increase the risk for HC in FA patients who received a CY based preparative therapy but these risk variants must be further evaluated in a larger population.

Economic and Clinical Burden of Virus-Associated Hemorrhagic Cystitis in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.

In this prospective observational study, we aim to investigate the role of cidofovir (CDV) as prophylactic treatment in preventing BK virus (BKV)-associated hemorrhagic cystitis (HC) in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). This study enrolled 28 patients who received prophylactic treatment with CDV following allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and 25 Allo-HSCT patients who received conventional supportive care, which included hydration and analgesics, from January 2020 to January 2022. Patients in the CDV prophylactic treatment group received intravenous injections of CDV at a dose of 1 mg/kg once a week for 4 weeks. PCR was used to detect the copy number of BKV (BKV-DNA) in the urine of all study participants at weeks 1, 2, 3, 4, and 5 after HSCT. From the third week onward, the BKV copy numbers in the CDV prophylactic treatment group were significantly lower than those in the conventional treatment group at subsequent time points. The proportion of patients with acute graft-versus-host disease (aGVHD), cytomegalovirus infection, and BKV copy numbers was significantly lower in the CDV group compared to the conventional treatment group. Additionally, the proportion of patients receiving CDV prophylactic treatment was significantly higher in the non-HC group. Receiver operating characteristic curve analysis indicated that BKV copy numbers could predict the occurrence and severity of HC. Furthermore, logistic regression analysis identified aGVHD, BKV copy numbers, and CDV prophylactic treatment as risk factors for the occurrence of HC in patients after Allo-HSCT. We identified for the first time in the literature that prophylactic treatment with CDV could significantly reduce the incidence of BKV-associated hemorrhagic cystitis.

BackgroundContinuous bladder irrigation (CBI) and proper adjustment of saline irrigation speed are important to avoid CBI failure in hemorrhagic cystitis (HC) patients after allogeneic hematopoietic stem cell transplantation (HSCT). Nevertheless, too fast irrigation speed could take away the patient's much heat, contribute to blood coagulopathy, and increase the nursing workload. Evaluation of risk for CBI failure remains an unmet clinical need.MethodsThe general information, clinical characteristics, and consultation records of HC patients in 1380 patients with hematopoietic stem cell transplantation in our center from 2017 to 2019 were analyzed retrospectively. The receiver operating characteristic (ROC) curve was used to calculate the cutoff point of the continuous variable, and multivariate logistic regression was used to analyze the risk factors affecting CBI failure in HC patients.ResultsThe incidence of HC after HSCT was 23%. A total of 227 patients with HC above grade 2 were included. Univariate analysis showed that CRP, age, platelet counts, onset time after transplantation, albumin, and hemoglobin were associated with CBI failure in the short-term (P < 0.05). ROC curve and multivariate logistic regression analysis showed that CRP > 8.89 ng/ml (RR = 7.828, 95% CI 2.885–21.244), age < 14.5 years (RR = 9.940, 95% CI 3.219–30.697), and onset time of HC > 37d after transplantation (RR = 7.021, 95% CI 2.204–22.364), were independent risk factors for failure of CBI (P < 0.05).ConclusionsThe study identified CRP > 8.89 ng/ml, age < 14.5 years, and onset time of HC after HSCT > 37d are independent factors for failure of CBI, which could be combined to allow stratification of HC after HSCT patients into low-, intermediate- and high-risk subgroups of CBI failure.

Comparison of Outcomes of HLA-Matched Related, Unrelated, or HLA-Haploidentical Related Hematopoietic Cell Transplantation following Nonmyeloablative Conditioning for Relapsed or Refractory Hodgkin Lymphoma

Hemorrhagic cystitis (HC) is a common complication after stem cell transplantation (SCT) that occurs more frequently in patients with Fanconi anemia (FA) because of hypersensitivity of their cells to the agents used in the preparation for SCT (chemo and radiation). Many HC cases respond to therapy with hyperhydration and maintenance of adequate platelet counts, but refractory cases may require additional measures such as the use of prostaglandins, alum, or hyperbaric oxygen (HBO). We report here an unusual complication to HBO therapy in a FA patient consisting of generalized edema mimicking capillary leak syndrome but with no pulmonary edema or ascites.

Hemorrhagic cystitis in a patient without a past history of radiation therapy who was treated with cabazitaxel for CRPC

Improved Outcomes Using Tacrolimus/Sirolimus for Graft-versus-Host Disease Prophylaxis with a Reduced-Intensity Conditioning Regimen for Allogeneic Hematopoietic Cell Transplant as treatment of Myelofibrosis

JC and BK polyomavirus-like particles as targets of innate and adaptive humoral immunity

Objective To investigate the efficacy and safety of the optimal alkalized hydration solution for hemorrhagic cystitis (HC) following unrelated donor allogeneic hematopoietic stem cell transplantation (URD-HSCT), and the risk factors and prophylaxis measures about HC.Methods The clinical data of 151 HC patients who underwent URD-HSCT were retrospectively analyzed. All patients were given busulfan/cyclophosphamide (BuCy)-based conditioning regimen.During Cy therapy, all patients were given the optimal alkalized hydration solution to prevent HC.MESNA was given intravenously after administration of Cy at 0, 3, 6, 9, 12 h, and its total dose was administration of Cy to 24 h under the ECG monitoring. Each 500 ml liquid contained 50 g/L sodium bicarbonate 20 ml. Urinary pH value was monitored every one hour (keeping urine pH＞7. 5). Results None of early onset HC occurred. Twenty-six of 151 (17. 2 %) patients developed late onset HC, and the median onset time was 40 (8～89) days after transplantation. During the therapy, no symptoms of the circulatory system, no congestive heart failure and no acid-base electrolyte imbalance occurred. All HC patients after re-hydration, diuretic, and (or) continuous bladder irrigation and other indwelling catheter after treatment, were cured. The statistical analysis showed that the following factors were significantly associated with HC: male (OR = 3. 093, 95 % CI, 1. 145～8.353, P＜0. 05), acute graft versus host disease (aGVHD) (OR= 18. 044, 95 % CI, 3. 952～～82. 392, P＜0. 01), and ≥30-yearold (OR = 6. 077, 95 0% CI, 1. 585～23. 299, P＜0. 01). Conclusion The optimal alkalized hydration solution is safe and effective to prevent early onset HC following URD-HSCT in combination with BuCy regimen. Male, aGVHD and ≥30-year-old were the risk factors for HC. Key words: Hematopoietic stem cell transplantation; Cystitis; Risk factors; Therapy

Effect of Cyclophosphamide on Hemorrhagic Cystitis Following Haploidentical Related Compared to Matched Related/Unrelated Donor Hematopoietic Stem Cell Transplantation: A 7-Year Tertiary Center Analysis