Risk Factors For Hemorrhagic Cystitis Research Articles

Risk factors for hemorrhagic cystitis in children undergoing hematopoietic stem cell transplantation: a systematic review and meta-analysis

BackgroundThe risk factors for hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT) are unclear. Therefore, we conducted this systematic review and meta-analysis to investigate the risk factors for HC in children undergoing HSCT.MethodsWe performed this meta-analysis by retrieving studies from PubMed, EMBASE, and the Cochrane Library up to October 10, 2023, and analyzing those that met the inclusion criteria. I2 statistics were used to evaluate heterogeneity.ResultsTwelve studies, including 2,764 patients, were analyzed. Male sex (odds ratio [OR] = 1.52; 95% confidence interval [CI], 1.16–2.00; p = 0.003, I2 = 0%), allogeneic donor (OR = 5.28; 95% CI, 2.60–10.74; p < 0.00001, I2 = 0%), human leukocyte antigen (HLA) mismatched donor (OR = 1.86; 95% CI, 1.00–3.44; p = 0.05, I2 = 31%), unrelated donor (OR = 1.58; 95% CI, 1.10–2.28; p = 0.01, I2 = 1%), myeloablative conditioning (MAC) (OR = 3.17; 95% CI, 1.26–7.97; p = 0.01, I2 = 0%), busulfan (OR = 2.18; 95% CI, 1.33–3.58; p = 0.002, I2 = 0%) or anti-thymoglobulin (OR = 1.65; 95% CI, 1.07–2.54; p = 0.02, I2 = 16%) use, and cytomegalovirus (CMV) reactivation (OR = 2.64; 95% CI, 1.44–4.82; p = 0.002, I2 = 0%) were risk factors for HC in children undergoing HSCT.ConclusionsMale sex, allogeneic donor, HLA-mismatched, unrelated donor, MAC, use of busulfan or anti-thymoglobulin, and CMV reactivation are risk factors for HC in children undergoing HSCT.

Exploring the Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Genitourinary Toxicities in Prostate Cancer Patients Undergoing Radiation Therapy: A Case Study and Discussion

Radiation therapy is a common treatment modality offered to patients with localized prostate cancer. It can be associated with early radiation-induced toxicities including dysuria, nocturia, frequency, urgency, spasm, and, rarely, hematuria. Early toxicities usually resolve once the treatment period has ended. Chronic toxicities are less common, and rarely, patients may experience radiation-induced hemorrhagic cystitis and hematuria months or years after radiation. We herein describe the case of a 65-year-old man with a past medical history of type-2 diabetes mellitus who experienced hemorrhagic cystitis for months following his radiation therapy. The patient was on sodium-glucose cotransporter-2 inhibitor therapy (empagliflozin), which we highlight as a potential risk factor for hemorrhagic cystitis. After cessation of Jardiance and initiation of semaglutide (GLP-1 agonist), his urinary symptoms significantly improved. To the best of our knowledge, this is the first such case reported.

Risk factors for hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation in a letermovir-exposed CMV-free population receiving PTCy.

Hemorrhagic cystitis (HC) is a highly impacting complication in allogeneic hematopoietic stem cell transplantation (HSCT), occurring in 12%-37% of patients. The impact of transplant- and patient-specific variables has been described, with a possible role for JCV and BKV, which may be cooperating with cytomegalovirus (CMV). Here, we analyze 134 letermovir-exposed, CMV-free patients, treated with the same cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, describing risk factors for HC. The overall incidence of HC was 23%. Patients with HLA mismatched transplant, higher comorbidity score, and receiving three alkylating agents with TBF (thiotepa, busulfan, and fludarabine) conditioning regimen had a higher risk of HC in multivariate analysis (OR: 4.48, 6.32, and 1.32, respectively). A HC-score including male gender, TBF conditioning, and HLA-mismatch stratifies the risk of HC in the first 100 days after HSCT. The role of BKV and JCV was not highly impacting in those patients, suggesting a possible synergistic effect between CMV and JCV in causing HC. HC can be interpreted as the combination of patient-related factors, chemotherapy-related toxicities-especially due to alkylating agents-and immunological elements.

Risk factors for hemorrhagic cystitis in children with β-thalassemia major after allogeneic hematopoietic stem cell transplantation

To explore the risk factors for hemorrhagic cystitis (HC) in children with β-thalassemia major (TM) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). A retrospective analysis was conducted on clinical data of 247 children with TM who underwent allo-HSCT at Shenzhen Children's Hospital from January 2021 to November 2022. The children were divided into an HC group (91 cases) and a non-HC group (156 cases) based on whether HC occurred after operation. Multivariable logistic regression analysis was used to explore the risk factors for HC, and the receiver operating characteristic curve was used to analyze the predictive efficacy of related factors for HC. Among the 247 TM patients who underwent allo-HSCT, the incidence of HC was 36.8% (91/247). Univariate analysis showed age, incompatible blood types between donors and recipients, occurrence of acute graft-versus-host disease (aGVHD), positive urine BK virus deoxyribonucleic acid (BKV-DNA), and ≥2 viral infections were associated with the development of HC after allo-HSCT (P<0.05). Multivariable analysis revealed that incompatible blood types between donors and recipients (OR=3.171, 95%CI: 1.538-6.539), occurrence of aGVHD (OR=2.581, 95%CI: 1.125-5.918), and positive urine BKV-DNA (OR=21.878, 95%CI: 9.633-49.687) were independent risk factors for HC in children with TM who underwent allo-HSCT. The receiver operating characteristic curve analysis showed that positive urine BKV-DNA alone or in combination with two other risk factors (occurrence of aGVHD, incompatible blood types between donors and recipients) had a certain accuracy in predicting the development of HC after allo-HSCT (area under the curve >0.8, P<0.05). Incompatible blood types between donors and recipients, occurrence of aGVHD, and positive urine BKV-DNA are risk factors for HC after allo-HSCT in children with TM. Regular monitoring of urine BKV-DNA has a positive significance for early diagnosis and treatment of HC.

CMV infection is a risk factor for hemorrhagic cystitis after hematopoietic stem cell transplantation.

Hemorrhagic cystitis (HC) is a common complication after transplantation. The purpose of this study was to examine the incidence and risk factors for HC after hematopoietic stem cell transplantation (HSCT). The records of patients who underwent allogenic HSCT from January 2012 to December 2018 at our institution were retrospectively reviewed. Cox proportional regression and Kaplan-Meier analyses were performed to determine independent risk factors for HC. The statistical analysis was performed in May 2020. A total of 173 patients underwent HSCT, and 53 (30.6%) developed grade 2 or 3 HC cystitis at a median of 37days (range - 5 to 98days) after transplantation. Thirty-two patients developed moderate (grade 2) cystitis and 21 severe (grade 3) cystitis. Of the 173 patients, 61 developed acute graft-versus-host disease (GVHD) (median onset day 24) and 79 experienced cytomegalovirus (CMV) reactivation (median onset day 35). The relative risk (RR) of developing a CMV infection for patients with acute GVHD was 2.77 times that of patients without acute GVHD (P < 0.001). CMV infection was the only independent variable significantly associated with HC in both univariate and multivariate analyses. The estimated hazard ratio (HR) of CMV infection for the development of HC was 5.57 (95% confidence interval [CI]: 2.52 to 12.33, P < 0.001). CMV infection is an independent risk factor for the development of HC after HSCT, and acute GVHD is a risk factor for CMV reactivation. Decreasing the frequency of GVHD after HSCT may result in a lower frequency of HC.

Outcomes and risk factors of hemorrhagic cystitis in pediatric allogeneic hematopoietic stem cell transplantation recipients using different graft source and condition with severe aplastic anemia

ABSTRACT Background Hemorrhagic cystitis (HC) is a severe complication of allo-HSCT, characterized by irritative symptoms of the urinary tract and a higher morbidity rate. The risk factors and prognosis of HC are still unclear. Objective The objective of this study is to identify risk factors and outcomes to improve treatment in pediatric SAA patients undergoing HSCTs in the Children's Hospital of Soochow University. Methods A total of 97 SAA patients as a cohort were enrolled from 2010 to 2019 in the Children's Hospital of Soochow University and a number of factors related to HC and outcomes were analysed. In all transplants (except UCBT), patients received a combination of G-CSF stimulated bone marrow (BM) and peripheral blood stem cell (PBSC). The minimum number of CD34 + cells is 5 × 106 cells/kg. Results Mononuclear cells dose (MNC, cut off: 8.53 × 108/kg) and grade II–IV acute graft versus host disease (aGVHD) were identified as independent risk factors for HC. Patients without HC had better overall survival (OS) than with HC (No HC: 98.6%±1.4% vs HC: 87.4% ± 6.8%, p = 0.03). Conclusion We concluded that aGVHD and MNC dose in graft might play an important role in the development of HC in pediatric SAA patients undergoing allo-HSCT. HC is also a key complication affecting the prognosis of children with SAA after allo-HSCT.

Urotoxicity and safety data of low-dose intravenous cyclophosphamide therapy for rheumatic diseases: A Single-Center retrospective cohort study

Despite its effectiveness in rheumatic diseases, cyclophosphamide (CYC) treatment should be used with caution due to its side effects. CYC is thought to pose a risk in the development of hemorrhagic cystitis and bladder cancer. This study aims to determine the incidence of hemorrhagic cystitis and bladder cancer with intravenous low-dose CYC therapy used in the treatment of rheumatic diseases. A total of 211 adult patients with rheumatic disease treated with intravenous CYC were evaluated in this retrospective study conducted between January 2006 and May 2021. Patient data including cumulative CYC dose, treatment frequency, duration of treatment, side effects, such as hemorrhagic cystitis and bladder cancer were acquired from medical archives. The mean follow-up period was 48.5 (3–180) months, and the mean cumulative CYC dose was 5g (2–19g). None of the patients received mesna therapy concurrent with CYC therapy. 11 patients developed hemorrhagic cystitis (5.2%). Hemorrhagic cystitis was found to be statistically significantly associated with the number of CYC cycles (p=0.04). All patients were asymptomatic. No statistically significant difference was observed between hemorrhagic cystitis, treatment duration, and cumulative dose for CYC therapy in rheumatic diseases. Malignancy developed in 12 patients (5.7%) after CYC treatment. Bladder cancer was observed in 1 patient. According to our findings, the only risk factor for hemorrhagic cystitis in patients receiving CYC was the number of CYC cycles. Intravenous CYC regimen did not cause symptomatic hemorrhagic cystitis. Low-dose IV CYC may be safe in terms of serious urotoxic side effects when used at the appropriate dose, duration and frequency.

Analysis of the Risk Factors for Hemorrhagic Cystitis after Hematopoietic Stem Cell Transplantation

To analyze the risk factors affecting hemorrhagic cystitis(HC) after allogeneic hematopoietic stem cell transplantation(allo-HSCT). The clinical data of 153 patients underwent allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2018 were selected and retrospectively analyzed. The incidence, median time and treatment outcome of HC should be observed. Multivariate analysis was used to observe the risk factors of HC in patients, including sex, age, diagnosis, disease status before transplantation, transplantation type, ATG and CTX in the pretreatment scheme, stem cell source, neutrophil and platelet implantation time; CMV, EBV and BKV infection, and acute graft-versus-host disease(aGVHD). Among 153 patients underwent allogeneic hematopoietic stem cell transplantation, 25 (16.34%) patients had HC, the median occurance time was 31 days, all patients achieved complete remission after treatment, no bladder irritation and bladder contracture were left. The results of univariate and multivariate Logistic regression analysis showed that the type of transplantation, ATG, CMV viremia before treatment, aGVHD (r=1.036, 3.234, 3.298 and 2.817, respectively) were the independent risk factors of HC. The urinary BKV detections in the patients with HC are positive, mainly occured during the period from day +13 to days +56. HLA haplotype, pretreatment including ATG, and CMV viremia, and aGVHD are the independent risk factors for HC after allo-HSCT.

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

Introduction: Hemorrhagic cystitis (HC) is a serious and common complication of hematopoietic cell transplantation (HCT) affecting both allogeneic (alloHCT) and haploidentical HCT recipients. Early urinary bleeding after transplant is usually attributed to toxic effects of cyclophosphamide (Cy) or other agents used in the conditioning regimen or for graft-versus-host disease (GVHD) prevention. HC occurring beyond 3 to 4 weeks after HCT is usually attributed to BK polyoma virus or other viruses, e.g. cytomegalovirus or adenovirus. The aims of this study were to determine the incidence, risk factors, severity, morbidity pattern and toxicity of treatment, and outcome of HC in recipients of HSCT at a single tertiary transplant center. Methods: We analyzed all patients undergoing haploidentical (haploHCT) or MRD/MUD alloHCT at our bone marrow transplant unit from September 2012 through June 2019. In alloHCT group, 70% (n=205) of the patients received myeloablative conditioning consisted of Cy and only six patients (2%) received identical GVHD prevention with a post-transplant Cy-based regimen. Conversely; in haploHCT group, use of Cy-containing preparative regimen was not often (22.9 % (n=8)) but 77.1% (n=27) of the patients received post-transplant Cy. Grading of HC was based on the system used by Droller et al. and classified as grade I if the hematuria was microscopic and grade II if macroscopic. The presence of clots in the urine was regarded as grade III and obstructive uropathy with or without renal impairment as grade IV HC, respectively. All patients with a clinical diagnosis of HC had urine and blood analyzed for presence of BK virus by PCR. Results: A total of 328 HSCTs were performed during the study period, of which 169 (51.5%) alloHSCT from MUD, 124 (37.8%) alloHCT from MRD and 35 (10.7%) haploHCT. Baseline characteristics of the patients were similar among two groups with regarding to age, diagnosis, disease status and intensity of conditioning (Table 1). Hemorrhagic cystitis was diagnosed in 78 of 328 patients (23.8%) with a median follow up 7.4 months. Disease status at transplant, recipient age, cytomegalovirus antigenemia and the intensity of conditioning regimen were not associated with the development of HC. In addition, use of bone marrow versus peripheral blood had no influence on development of hemorrhagic cystitis (p=0.16). The incidence of HC was significantly higher in patients who received grafts from haploidentical donors compared to those receiving grafts from MRD/MUDs (54.3% (n=19) vs 20.1% (n=59), p&lt;0.001). Interestingly, the incidence of Grade III-IV HC was higher in the alloHCT compared to the haploHCT groups (37.2% vs 2.1%, p&lt;0.001). In multivariate analysis of risk factors associated with HC, receiving conditioning regimen including Cy and the use of a haploidentical donor was not significantly associated with HC. The incidence HC with BK viruria at the time of diagnosis of HC was higher in the cohort of patients receiving grafts from MRD/MUD donors (61% vs 47%, p=0.04). and BK viruria was not associated with HC severity. We identified no significant association between adenovirus, HHV-6 or CMV in HC patients comparing the onset and resolution of HC. Neither HC nor grades III-IV HC was associated with overall survival. Conclusion: Conditioning regimen is an important factor in the development of HC and its mechanism has been well described. In our study, we could not demonstrate the increased HC risk of conditioning regimens including cyclophosphamide. We also showed that cyclophosphamide in MAC had similar HC risk compared with RIC containing cyclophosphamide. BK virus was frequently found to be a risk factor for HC. In this retrospective analysis, BK virus was detected 45 patients out of 78 patients with HC and BK viruria was not associated with HC severity. Table 1 Disclosures Özcan: Amgen: Honoraria, Other: Travel support; Novartis: Research Funding; Celgene Corporation: Research Funding, Travel support; MSD: Research Funding; AbbVie: Other: Travel support, Research Funding; Jazz: Other: Travel support; Janssen: Other: Travel support, Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding; Archigen: Research Funding; Roche: Other: Travel support, Research Funding; Bayer: Research Funding; Sanofi: Other: Travel support; Abdi Ibrahim: Other: Travel support; BMS: Other: Travel support. Beksac:Celgene: Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Low incidence of hemorrhagic cystitis following ex vivo T-cell depleted haploidentical hematopoietic cell transplantation in children

Hemorrhagic cystitis (HC) is a debilitating complication following allogenic hematopoietic cell transplantation (HCT). HLA disparity and T-cell depletion have been implicated as risk factors for HC. However, reports on the incidence and risk factors for HC in ex vivo T-cell depleted haploidentical HCT (haploHCT) in children are lacking. We studied 96 haploHCT procedures performed in 83 children between 2002 and 2017. Sixty-three patients were diagnosed with a malignant disease and 20 with nonmalignant disease. All but three patients with SCID underwent myelotoxic and/or lymphotoxic conditioning therapy. Grafts were CD3+ (36.5%) or TcRαβ+ (63.5%) depleted to prevent graft versus host disease (GvHD). Fourteen patients (14.6%) were diagnosed with HC; 12 (12.5%) had clinically significant stage II-IV HC. All patients with HC had BK viruria and/or viremia. Increasing age and chemotherapeutic treatment prior to conditioning were identified as risk factors for HC. Immune recovery did not significantly differ between patients with and without HC. Thus, we report a low incidence of HC in pediatric haploHCT using ex vivo T-cell depletion. The combination of a reduced toxicity conditioning regimen, and typically absent pharmaceutical post-HCT GvHD prophylaxis in our patients might have contributed to the decreased the risk of HC, despite HLA disparity.

Clinical features and risk factors of hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

目的探讨异基因造血干细胞移植（allo-HSCT）患者出血性膀胱炎（HC）发生的相关因素、治疗措施和预后。方法对2010年1月1日至2017年5月31日期间425例接受allo-HSCT的患者进行回顾性分析。结果①全部425例患者中，男262例，女163例，中位年龄26（2~56）岁；急性髓系白血病（AML）138例，急性淋巴细胞白血病（ALL）96例，骨髓增生异常综合征（MDS）29例，重型再生障碍性贫血（SAA）98例，慢性髓性白血病（CML）64例；同胞全相合移植221例，无关供者移植89例，单倍型移植115例。②108例（25.41%）患者发生HC，中位发生时间为移植后32（3~243）d，中位持续时间20（3~93）d；Ⅰ级33例（30.56%），Ⅱ级49例（45.36%），Ⅲ级21例（19.44%），Ⅳ级5例（4.63%）。③108例发生HC的患者中，103例治愈，5例无效，12例患者死于移植相关并发症（感染、复发、重度急性GVHD、继发植入失败）。④单因素分析显示：年龄<30岁、移植类型、CMV血症、急性GVHD与HC发生有相关性。多因素分析显示，急性GVHD是allo-HSCT患者发生HC的独立危险因素。结论allo-HSCT后合并HC患者的总体预后较好。

Clinical analysis of hemorrhagic cystitis in children and adolescents with hematological diseases post haplo-hematopoietic stem cell transplantation

目的观察儿童及青少年血液病患者单倍型造血干细胞移植（haplo-HSCT）后出血性膀胱炎（HC）的临床特征并探讨其影响因素。方法回顾性分析2015至2016年接受haplo-HSCT的89例儿童及青少年血液病患者的临床资料。结果全部89例患者中，≤14岁62例（儿童组）、>14~<18岁27例（青少年组）；男56例，女33例；中位移植年龄10（1~17）岁；急性淋巴细胞白血病（ALL）44例，急性髓系白血病（AML）33例，急性混合细胞白血病（AHL）3例，骨髓增生异常综合征（MDS）9例。移植物来源均为骨髓+外周血干细胞。全部89例患者中32例（36%）发生HC，其中迟发型31例，早发型1例；Ⅰ度6例、Ⅱ度16例、Ⅲ度8例、Ⅳ度2例；HC发病中位时间为移植后25（2~55）d，中位持续时间为19（3~95）d；所有患儿均获得治愈。儿童组HC发病率低于青少年组[27.4%（17/62）对55.6%（15/27），χ2=6.466，P<0.05]。儿童组中<5岁组HC发生率低于5~14岁组[0（0/12）对34%（17/50），χ2=4.043，P<0.05]。结论HC是儿童及青少年血液病患者haplo-HSCT的常见并发症，总体预后良好，年龄是其发生的影响因素。

Aetiology of hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

Incidence, severity, and risk factors for hemorrhagic cystitis (HC) were assessed in 267 patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). HC was diagnosed in 14.6% (39 patients) within 1-139 days after allo-HSCT (median duration – 39 days). Chemotherapy-related HC was diagnosed in 4 patients only. The majority (19⁄35) of patients developed late HC of viral aetiology. Median time from a day of HC diagnosis to clinical symptoms resolution was 25 days (range: 6 to 133 days). Using a multivariate analysis, allo-HSCT from mismatched unrelated/haploidentical donor was found to be a risk factor of HC (р=0.01). The analysis also showed that 82.1% of patients with HC received cyclophosphamide as a part of conditioning regimen or +3/+4 days after allo-HSCT.

Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients.

Hemorrhagic cystitis (HC) is a common complication after hematopoietic allogeneic stem cell transplantation (HSCT) associated with intensity of the conditioning regimen, cyclophosphamide (Cy) therapy, and BK polyomavirus (BKPyV) infection. We analyzed 33 consecutive haploidentical (haplo) HSCT recipients transplanted for hematologic diseases. Eleven patients had a previous transplant. Median follow-up was 11 months. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine + mycophenolate mofetil and post-HSCT Cy. Thirty-two of 33 patients achieved neutrophil recovery. Cumulative incidence (CI) of platelet recovery was 65%. CI grade II-IV acute GVHD was 44%. Twenty patients developed HC in a median time of 38 days. CI of HC at day 180 was 62%. BKPyV was positive in blood and urine of 91% of patients at HC onset. HC resolved in 18/20 patients. Factors associated with HC were previous transplant (P = 0.01) and occurrence of cytomegalovirus reactivation before HC (P = 0.05). Grade II-IV acute GVHD was not associated with HC (P = 0.62). CI of day 180 viral infections was 73%. Two-year overall survival (OS) was 50%; HC did not impact OS (P = 0.29). The incidence of HC after haplo with post-HSCT Cy is high and is associated with morbidity, especially in high-risk patients such as those with a previous transplant history and with impaired immune reconstitution.

Incidence of Cyclophosphamide-induced Urotoxicity and Protective Effect of Mesna in Rheumatic Diseases.

To assess bladder toxicity of cyclophosphamide (CYC) and uroprotective effect of mesna in rheumatic diseases. Data of 1018 patients (725 women/293 men) treated with CYC were evaluated in this retrospective study. All of the following information was obtained: the cumulative CYC dose, route of CYC administration, duration of therapy, concomitant mesna usage, and hemorrhagic cystitis. Cox proportional hazard model was used for statistics. We identified 17 patients (1.67%) with hemorrhagic cystitis and 2 patients (0.19%) with bladder cancer in 4224 patient-years. The median time for diagnosis to hemorrhagic cystitis was 10 months (4-48) and bladder cancer was 8 years (6-10.9). There were 583 patients (57.2%) who received mesna with intravenous CYC therapy. We observed similar incidence rate for hemorrhagic cystitis in both patient groups concomitantly treated with or without mesna [9/583 (1.5%) vs 8/425 (1.8%) respectively, p = 0.08]. Cumulative CYC dose (HR for 10-g increments 1.24, p < 0.001) was associated with hemorrhagic cystitis. Cumulative dose was the only risk factor for hemorrhagic cystitis in patients treated with CYC. No proof was obtained for the uroprotective effect of mesna in our cohort.

Risk factors for hemorrhagic cystitis in pediatric allogeneic hematopoietic stem cell transplant recipients.

Hemorrhagic cystitis (HC) results in significant morbidity among hematopoietic stem cell transplant (HSCT) recipients. Several potential causes for HC have been postulated, including viral infection, but definitive evidence is lacking, particularly in pediatric HSCT patients. Ninety pediatric HSCT recipients were prospectively tested on a weekly basis for adenovirus (ADV) and BK virus (BKV) by quantitative real-time polymerase chain reaction in blood and urine samples. Results were correlated with the occurrence of grade II-IV HC. The odds ratio (OR) of HC (95% confidence interval) for BKV ≥1×10(9) copies/mL of urine was 7.39 (1.52, 35.99), with a P-value of 0.013. Those with acute graft-versus-host disease (aGVHD) also had higher odds of developing HC, with an OR of 5.34. Given a 20% prevalence rate of HC, positive and negative predictive values of 29% and 95% were seen with a cutoff of 10(9) copies/mL. BK viremia did not reach significance as a risk factor for development of HC (P=0.06). Only 8 patients showed ADV viruria and 7 showed ADV viremia; all had low viral loads and 4 had no evidence of HC. HC in pediatric HSCT is correlated most strongly to elevated urinary viral load of BKV and to aGVHD, but less strongly to BK viremia.

Relationship of BK Polyoma Virus (BKV) in the Urine with Hemorrhagic Cystitis and Renal Function in Recipients of T Cell–Depleted Peripheral Blood and Cord Blood Stem Cell Transplantations

Hematopoietic stem cell transplant (HSCT) recipients are at significant risk for BK virus (BKV) reactivation, hemorrhagic cystitis (HC), and renal dysfunction. We prospectively monitored 98 patients who had received HSCT by serial BKV PCR in the urine through day (D) +100 to analyze the relationship between BK viruria and HC, serum creatinine (Cr), and creatinine clearance (CrCl) through D +180 or death. Patients, median age 52 years (range, 20 to 73), received T cell–depleted (50%) or cord blood allografts (21%). Median pre-HSCT BKV IgG titers were 1:10,240. Incremental increase in BKV IgG titers correlated with developing BK viruria ≥ 107 copies/mL. By D +100, 53 (54%) patients had BK viruria. BKV load in the urine increased at engraftment and persisted throughout D +100. HC developed in 10 patients (10%); 7 of 10 with BK viruria. In competing risk analyses, BK viruria ≥ 107 copies/mL, older age, cytomegalovirus reactivation, and foscarnet use were risk factors for HC. Cr and CrCl at 2, 3, and 6 months after HSCT were similar between patients with and without BK viruria.

Risk Factors and Predictors of Severity Score and Complications of Pediatric Hemorrhagic Cystitis

We retrospectively analyzed our institutional incidence of hemorrhagic cystitis, identified risk factors, and examined associations of risk factors with disease severity and genitourinary complication rates. We reviewed charts of all consecutive pediatric patients treated from 1986 to 2010. We analyzed demographics, underlying diagnosis and treatment data to assess risk factors for hemorrhagic cystitis. We also correlated disease severity scores with clinical predisposing factors, and performed univariate and multivariate analyses to examine associations between risk factors and outcomes. Hemorrhagic cystitis was observed in 97 of 6,119 children (1.6%), most of whom (75%) had severity scores of II or III. Mean ± SD age was 12.2 ± 6.3 years for patients with hemorrhagic cystitis and 10.5 ± 7 years for patients without hemorrhagic cystitis (p = 0.017). On univariate analysis increased risk of hemorrhagic cystitis was significantly associated with age greater than 5 years, male gender, cyclophosphamide or busulfan chemotherapy, bone marrow or peripheral blood stem cell transplantation, pelvic radiotherapy and underlying diagnoses of rhabdomyosarcoma, acute leukemia and aplastic anemia. On multivariate analysis age greater than 5 years, allogeneic bone marrow or peripheral blood stem cell transplantation and pelvic radiotherapy were significantly associated with increased risk of hemorrhagic cystitis. Older age, late onset hemorrhagic cystitis, positive urine culture for BK virus and bone marrow or peripheral blood stem cell transplantation were associated with greater disease severity. Patients with higher severity scores more frequently experienced bladder perforation, hydronephrosis, overall hemorrhagic cystitis complications, and increased creatinine and blood urea nitrogen levels during followup. Older age, previous bone marrow or peripheral blood stem cell transplantation and BK virus in the urine are risk factors for hemorrhagic cystitis and are associated with a higher severity score. Higher severity scores are associated with increased rates of genitourinary complications and renal impairment.

BK Viremia Precedes Hemorrhagic Cystitis in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

BK virus is associated with hemorrhagic cystitis after hematopoietic stem cell transplantation (HSCT), although evidence supporting a causal relationship remains limited. Although BK viruria is common after HSCT, BK viremia may better predict clinically significant cystitis, similar to its predictive value for nephropathy after kidney transplantation. We hypothesized that BK viremia would precede hemorrhagic cystitis in a cohort of 88 consecutive children prospectively enrolled to originally study thrombotic microangiopathy in the first 100 days after allogeneic HSCT. Cox regression models with time-varying covariates assessed the association between different BK viremia cutoffs and the development of hemorrhagic cystitis, defined as at least macroscopic hematuria. Subjects with a peak plasma BK viral load 1 to 9999 copies/mL had an adjusted hazard ratio of 4.2 (95% confidence interval (CI), 1.3 to 13.7) for the development of hemorrhagic cystitis. Those with peak BK viremia >100,000 copies/mL had an adjusted hazard ratio of 116.8 (95% CI, 12 to 1136) for cystitis. Other independent risk factors for hemorrhagic cystitis included age >7 years and HHV-6 viremia. Neither graft-versus-host disease nor achieving engraftment increased the risk for cystitis. If therapeutic strategies are found to be effective, these observations may support screening for BK viremia after HSCT, as currently recommended for other DNA viruses.

Risk Factors and Clinical Outcome of Thrombotic and Bleeding Complications in 527 Patients Following Hematopoietic Stem-Cell Transplantation (HSCT)

Abstract 3076 Background:Hemostatic disorders are common and potentially fatal complications in patients undergoing hematopoietic stem-cell transplantation (HSCT). Limited data exist on early diagnosis and prevention of these complications. In this study, we retrospectively investigated the outcome and risk factors associated with thrombotic and bleeding complications in HSCT recipients. Methods:From April 2004 to December 2010, 527 hematologic patients receiving HSCT (126 Auto-HSCT and 401 Allo-HSCT) were enrolled in the study, and their clinical manifestation and laboratory parameters were analyzed for evaluating the outcome of hemostatic complications and related risk factors. All analyses were carried out using the SAS program (version 8.1). Results:Overall incidence of thrombotic complication, which included 9 veno-occlusive diseases (VOD), 1 transplantation related thrombotic microangiopathy (TA-TMA), 1 pulmonary embolism (PE) and 1 deep vein thrombosis (DVT), was 2.3% (12 cases), and occurred in 11 patients who received allogeneic HSCT, and 1 patient who received autologous HSCT. The overall mortality after thrombotic events was 75% (9 cases) in all HSCT recipients with thrombotic complications. A total of 382 HSCT recipients (72.5%) developed bleeding events, including minor bleeding of 67.1% (210 cases), moderate bleeding of 28.4% (89 cases), and severe bleeding of 4.5% (14 cases) of all bleeding patients. By bleeding sites, 183 patients developed hemorrhagic cystitis (34.7% of all HSCT recipients). Other organs of hemorrhage involved skin or mucosa (46.5% of all HSCT recipients), gastrointestinal tract (21.1%), vagina (9.3%), and respiratory tract (1.3%). By risk factors analysis, CD33 mAb use and preparative regimen containing total body irradiation were significantly associated with the occurrence of thrombotic disorders (P<0.05). Thrombocytopenia, grade 2–4 acute graft-versus-host disease (aGVHD), allogeneic transplantation and infection were independent risk factors for bleeding complication (P<0.05). Polyomavirus and grade 2–4 aGVHD were risk factors for hemorrhagic cystitis (P<0.05). The number of hemorrhagic sites was significantly correlated with bleeding severity (P<0.05). Neither thrombotic nor bleeding disorders was correlated with age, disease category, gender, transplantation types, routine hemostatic parameters, or biochemical indicators (P>0.05). Survival rate was correlated with the bleeding site and intensity of bleeding disorders (P<0.01). Respiratory and gastrointestinal bleeding independently increased the mortality of HSCT recipients, while overal cumulative survival was decreased in patients with thrombotic complications. In addition, PAI-1 level in the HSCT recipients with thrombotic complications were significantly higher than other complications, including GVHD, infections, and preparative regimen-related toxicity (P<0.01). Conclusions:Our study suggested that HSCT patients with thrombotic complications experienced high mortality while the HSCT recipients with bleeding disorders had high morbidity. Hence, early diagnosis and therapy of hemostatic complications are crucial to improve the prognosis of HSCT recipients. Disclosures:No relevant conflicts of interest to declare.