Endoscopic management of severe hemorrhagic cystitis after HSCT: experience from a high-volume center in China

Endoscopic management of severe hemorrhagic cystitis after HSCT: experience from a high-volume center in China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Endoscopic management of severe hemorrhagic cystitis after HSCT: experience from a high-volume center in China Lizhe An, Yang Hong, Luping Yu, Tao Xu, Jun Kong This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6495700/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: To describe endoscopic features, surgical techniques, and prognostic factors of severe hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), based on experience from a high-volume center in China. Methods: A retrospective analysis was conducted of 50 patients with severe HC who underwent endoscopic electrocautery from 2014 to 2023. Severe HC was defined as requiring urgent intervention after failed conservative management and was classified into three endoscopic grades based on the burden of blood clots. Grade III cases were treated using a “cyclical” technique. Patients were grouped by surgical outcomes for comparison. Results: Among 50 patients (56% male; median age 32.5 years), the median onset of HC was 31 days after Allo-HSCT, and the preoperative duration was 61 days. Endoscopy revealed grade III HC in 64%, extensive bladder mucosal involvement in 84%, and trigone involvement in 16%. Lesions commonly involved the posterior and anterior walls. The median operative time was 55 minutes. Complete remission was achieved in 58% of patients. Compared with the complete group, the non-complete group had higher neutrophil-to-lymphocyte ratio (NLR), D-dimer, and more frequent hydronephrosis and trigone involvement. Hydronephrosis and trigone involvement independently predict poor outcomes, and preoperative NLR has moderate predictive value (AUC = 0.718; cutoff = 4.555). Conclusion: Severe HC after Allo-HSCT requires timely endoscopic intervention. Most cases present as grade III and can be effectively managed using the “cyclical”technique. Hydronephrosis and trigone involvement are independent risk factors for poor outcomes, and preoperative NLR has moderate predictive value. Allogeneic hematopoietic stem cell transplantation Hemorrhagic cystitis Endoscopic Surgical techniques Prognostic factors Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Hemorrhagic cystitis (HC) is a frequent complication following allogeneic hematopoietic stem cell transplantation (Allo-HSCT), with an incidence ranging from 12.2% and 36.9% [ 1 ]. In severe cases, HC may result in bladder tamponade, progressive hemoglobin decline, and hemodynamic instability, requiring urgent surgical intervention. Endoscopic clot evacuation and mucosal coagulation remain the mainstay of treatment [ 2 , 3 ]. However, thrombocytopenia, coagulopathy, and leukopenia are common in post-transplant patients, often accompanied by rapid and profuse hematuria, making endoscopic management particularly challenging. Although severe HC is clinically significant, existing studies on endoscopic management after Allo-HSCT are limited, with small sample sizes and insufficient characterization of cystoscopic findings, surgical techniques, and prognostic factors [ 4 , 5 ]. We conducted a retrospective study of patients with severe HC who underwent endoscopic treatment at a high-volume hematology center in China. Endoscopic features were systematically described and used to grade the severity of HC. A “cyclical” technique combining suction, coagulation and irrigation was employed in cases with extensive bleeding and clot burden. Prognostic analysis was performed to identify factors associated with non-complete remission. To our knowledge, this study represents the largest single-center cohort to date on endoscopic treatment of HC after Allo-HSCT and provides detailed insight into intraoperative findings, surgical techniques, and outcome-related risk factors. 2. Methods 2.1. Clinical data The medical records of patients who underwent Allo-HSCT at our center between January 2014 and December 2023 were retrospectively reviewed. Patients who developed severe HC and received endoscopic treatment were included. Severe HC was defined as gross hematuria refractory to conservative measures, accompanied by bladder tamponade or a rapid decline in hemoglobin requiring urgent intervention. Demographic characteristics, transplantation-related variables, preoperative laboratory findings (including inflammatory, coagulation, renal function, and infectious parameters), imaging results, and endoscopic features were collected. Surgical outcomes were classified as complete remission, partial remission, or no remission. Complete remission was defined as the complete resolution of gross hematuria; partial remission as persistent hematuria not requiring further invasive treatment; and no remission as requiring reoperation or other invasive interventions. Patients under 18 years, those with incomplete records, or those who did not undergo surgery due to contraindications were excluded. The study was approved by the Ethics Committee of Peking University People's Hospital (No. 2024PHB170-001). 2.2. Surgical techniques Under general anesthesia, patients were positioned in lithotomy. A resectoscope (26F sheath) was introduced transurethrally to assess mucosal bleeding and clot size. HC was classified into three grades based on cystoscopic findings. Grade I, with no clots, allowed for immediate electrocoagulation and was the least complex. Grade II, with small number of clots, clots were removed via resection loop or washed out by Ellik bladder evacuator before electrocoagulation. Grade III, with extensive clots filled with bladder, was the most complex and required a "cyclical" technique to balance hemostasis and clot removal. The main steps for the "cyclical" technique are as follows. The scope is withdrawn, leaving the sheath in place. A 10F suction catheter connected to vacuum is then introduced through the sheath to aspirate and break down larger clots (Fig. 1 ), while smaller clots are flushed out using Ellik bladder evacuator. Given the fragile bladder mucosa in HC patients, gentle handling is crucial when using Ellik bladder evacuator to avoid bladder rupture due to excessive irrigation pressure. After partial clot removal, the scope is reinserted, and electrocoagulation is applied to visible bleeding lesions while avoiding damage to the ureteral orifices (Fig. 2 ). Bladder tissue found in the flushed clots is sent for pathological examination. Clots removal and electrocoagulation are alternated until bleeding is controlled, indicated by a clear endoscopic view (Fig. 3 ) and clear or light red irrigation fluid. Bladder mucosa is preserved as much as possible while ensuring effective hemostasis. Any remaining clots are removed using Ellik bladder evacuator or resection loop. Finally, a three-way Foley catheter is placed for continuous bladder irrigation. Patients stayed in the hematology ward for continued care. Bladder irrigation stopped after three days of clear fluid, and the catheter was removed after seven days without bleeding. If bleeding worsened, repeat endoscopic hemostasis was performed. See Fig. 4 for the treatment flowchart. 2.3 Statistics All statistical analyses were performed using SPSS version 30.0. Continuous variables were tested for normality using the Shapiro–Wilk test. Data were expressed as mean ± standard deviation or median (interquartile range), and compared using the independent samples t-test or the Mann–Whitney U test, as appropriate. Categorical variables were compared using the chi-square test or Fisher’s exact test. Variables with P < 0.05 in univariate analysis were included in a multivariate logistic regression model. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of selected variables. A two-sided P < 0.05 was considered statistically significant. 3. Results 3.1 Patient characteristics and endoscopic features Between January 2014 and December 2023, a total of 6,836 patients underwent allogeneic hematopoietic stem cell transplantation Allo-HSCT at our center. HC occurred in 1,668 patients (24.4%), of whom 69 (1.0%) developed severe HC as defined in this study, accounting for 4.1% of all HC cases. Fifty patients who received endoscopic treatment for severe HC were included in the final analysis. The median age was 32.5 years (IQR 23–44), and 56% were male. The most common primary hematologic diseases were acute lymphoblastic leukemia (48%) and acute myeloid leukemia (22%). The median onset of HC was 31 days (IQR 22–45) after transplantation, with a median duration of 61 days (IQR 35–89). Viral infection was the most frequently suspected cause (64%). The primary indications for surgery were progressive hemoglobin decline (58%), bladder tamponade (8%), or both (34%). Most patients (92%) required perioperative blood transfusion. The median operative time was 55 minutes (IQR 40–95). On cystoscopy, 64% of patients had grade III HC. Bladder mucosal involvement exceeded 50% in 84% of cases, and the bladder trigone was involved in 16%. Lesions were most commonly located on the posterior wall (58%), anterior wall (52%), right wall (50%), left wall (40%), and dome (40%). Among the 50 patients, complete remission was achieved in 29 (58%), partial remission in 14 (28%), and no remission in 7 (14%). Detailed clinical characteristics are summarized in Table 1. 3.2 Comparison of clinical parameters between complete and non-complete remission groups Patients were divided into two groups based on surgical outcomes: complete remission (n = 29) and non-complete remission (n = 21). As shown in Table 2, no significant differences were observed between the two groups in terms of age, sex, primary hematologic disease, onset or duration of HC, or most routine laboratory parameters. However, patients in the non-complete remission group had significantly higher preoperative neutrophil count (median 3.18 vs. 2.19 ×10⁹/L, P = 0.046), neutrophil-to-lymphocyte ratio (NLR) (median 6.51 vs. 3.14, P = 0.009), and D-dimer levels (median 436 vs. 263.5 ng/mL, P = 0.041). Regarding endoscopic and imaging findings, hydronephrosis was more common in the non-complete remission group (47.6% vs. 10.3%, P = 0.003). In addition, patients in this group had a significantly higher rate of grade III HC (71.4% vs. 41.4%, P = 0.035) and bladder trigone involvement (28.6% vs. 6.9%, P = 0.048). There were no significant differences in operative time and extent of mucosal involvement. Detailed comparisons are summarized in Table 2. 3.3 Multivariate analysis of risk factors for non-complete remission Multivariate logistic regression was conducted to identify independent predictors of non-complete remission. As shown in Table 3, hydronephrosis (odds ratio [OR] = 11.07, 95% confidence interval [CI]: 1.87–65.56, P = 0.008) and involvement of the bladder trigone (OR = 10.69, 95% CI: 1.07–106.61, P = 0.043) were independently associated with an increased risk of non-complete remission. Although the neutrophil-to-lymphocyte ratio (NLR) showed a trend toward significance (OR = 1.206, 95% CI: 0.988–1.472, P = 0.065), it did not meet the statistical threshold. Other variables, including neutrophil count (OR = 0.959, P = 0.787), D-dimer (OR = 1.001, P = 0.119), and endoscopic grade of HC (grade III vs. I–II: OR = 3.579, P = 0.109), were not independently associated with treatment outcome. 3.4 Predictive value of NLR for surgical outcome Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of preoperative NLR for non-complete remission. The area under the curve (AUC) was 0.718 (95% CI: 0.581–0.854, P = 0.012), indicating moderate discriminative ability. The optimal cutoff value of NLR was 4.555, which yielded a sensitivity of 71.4% and a specificity of 72.4% (Figure 5). 4. Discussions The incidence of HC after Allo-HSCT was reported 12.2% and 36.9% [1]. According to large sample data of our center, the incidence was 24.1%, with 1% developing severe HC, highlighting the need for timely intervention. Conservative treatments such as hydration and bladder irrigation are suitable for mild cases [6]. Intravesical agents and hyperbaric oxygen therapy have been reported but are limited by delayed efficacy and poor accessibility [7, 8]. Endoscopic management is the preferred approach for severe HC requiring timely hemostasis, while cystectomy is reserved for refractory cases due to its invasiveness [4]. Most existing studies focus on radiation-induced HC [9, 10], and data on Allo-HSCT-related HC remain limited. This study presents the largest cohort to date on endoscopic management of HC after Allo-HSCT, with characterization of endoscopic findings, surgical techniques, and associated prognostic factors. Severe cases were often marked by heavy bleeding and poor visibility. Traditional methods, such as Ellik evacuators and ultrasonic probes, were ineffective. We adopted a “cyclical” technique using vacuum-assisted suction for clot removal, followed by electrocoagulation. This approach enabled efficient hemostasis, with a median operative time of 108 minutes in Grade III cases. Given that 28% of patients achieved only partial remission and 14% had no remission after endoscopic treatment, early identification of high-risk individuals is essential to guide postoperative management. Therefore, we analyzed clinical and endoscopic factors associated with surgical outcomes by comparing patients with complete and non-complete remission. Significant differences were observed in preoperative neutrophil-to-lymphocyte ratio, D-dimer levels, hydronephrosis, and bladder trigone involvement. NLR is a marker of systemic inflammation that reflects the balance between inflammation and immunity, and has shown prognostic value in various inflammatory conditions [11, 12]. In our study, elevated preoperative NLR was associated with poor surgical outcomes, possibly reflecting a more intense inflammatory response within the bladder mucosa. Similarly, elevated D-dimer level was also linked to poor prognosis. D-dimer is a fibrin degradation product that reflects activation of coagulation and fibrinolysis, and has been associated with adverse outcomes in conditions such as gastrointestinal and intracerebral hemorrhage [13, 14]. Its elevation in severe HC may indicate greater mucosa injury or ongoing bleeding. Unlike radiation-induced cystitis [10], which typically affects the bladder trigone due to localized pelvic exposure, trigone involvement was relatively uncommon in HC after Allo-HSCT, likely due to its viral-mediated pathogenesis. However, when present—especially alongside hydronephrosis—it often indicated extensive urothelial involvement and was associated with worse prognosis. In addition to laboratory and imaging indicators, our study also highlighted the prognostic value of intraoperative findings. Patients with grade III hemorrhagic cystitis had significantly lower remission rates, underscoring the importance of endoscopic assessment in guiding management and predicting outcomes. Consistent with these observations, multivariate logistic regression confirmed both trigone involvement and hydronephrosis as independent risk factors for non-complete remission (Table 3). Although NLR did not reach statistical significance in multivariate analysis, given its clinical relevance and a p-value near the significance threshold, we performed ROC analysis to further evaluate its predictive utility. The resulting AUC of 0.718 suggests moderate discriminative ability, and the identified cutoff value of 4.555 may provide a useful reference for preoperative risk stratification in clinical settings (Figure 5). Our study had several limitations. Firstly, it was a single-center retrospective analysis; however, as one of the largest hematology centers in China, the sample size is sufficient. Secondly, electrocoagulation was the only method employed for hemostasis, lacking a comparison with laser or other energy platforms. Lastly, while this study focused on short-term outcomes, it lacked long-term follow-up data, which is essential for evaluating postoperative bladder function. 5. Conclusions This single-center study presents the largest cohort to date on endoscopic management of severe HC after Allo-HSCT. A “cyclical” technique was developed to improve efficiency of clot removal and hemostasis under poor endoscopic visibility. An endoscopic grading system was established to reflect intraoperative complexity, and higher grades were associated with worse outcomes. Prognostic analysis further identified hydronephrosis and trigone involvement as independent risk factors, while preoperative NLR demonstrated moderate predictive value for surgical response. These findings may support risk-adapted surgical and postoperative strategies. Declarations Conflict of Interest: None Author(s) Participation: LZ An: Data collection and Manuscript writing. Y Hong: Data collection. LP Yu: Data management. T Xu: Project development. J Kong: Project development and manuscript editing. References Galli E, Metafuni E, Gandi C, et al (2024) Risk factors for hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation in a letermovir-exposed CMV-free population receiving PTCy. Eur J Haematol 112:577–584. https://doi.org/10.1111/ejh.14147 Tirindelli MC, Flammia GP, Bove P, et al (2014) Fibrin glue therapy for severe hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 20:1612–1617. https://doi.org/10.1016/j.bbmt.2014.06.018 Sakurada M, Kondo T, Umeda M, et al (2016) Successful treatment with intravesical cidofovir for virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A case report and a review of the literature. J Infect Chemother 22:495–500. https://doi.org/10.1016/j.jiac.2016.01.013 Hayashida M, Nishida A, Kuno M, et al (2024) Novel Insights into Predictors, Optimized Treatments, and Prognosis Factors for Virus-Induced Hemorrhagic Cystitis Post-Hematopoietic Stem Cell Transplantation: A Single-Institution Study of 427 Japanese Patients. Blood 144:2162–2162. https://doi.org/10.1182/blood-2024-199936 Tang FF, Zhang XH, Chen H, et al (2017) [Surgical treatment of severe, refractory hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation: a report of 17 patients]. Zhonghua Nei Ke Za Zhi 56:414–418. https://doi.org/10.3760/cma.j.issn.0578-1426.2017.06.006 Yang W-B, Du Y-Q, Bai W-J, et al (2021) Multivariate analysis of factors predicting surgical intervention for hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Chin Med J (Engl) 134:1480–1482. https://doi.org/10.1097/CM9.0000000000001295 Yozgat AK, Bozkaya IO, Aksu T, et al (2022) Analysis of Hemorrhagic Cystitis and BK Viremia in Children after Hematopoietic Stem Cell Transplantation. Indian J Transplant 16:174. https://doi.org/10.4103/ijot.ijot_84_21 Jiang Y, Chen H, Fang X, et al (2020) Hyperbaric Oxygen Therapy for Late-Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation and Effective Factors Prediction. Blood 136:27–28. https://doi.org/10.1182/blood-2020-136891 Zhu J, Xue B, Shan Y, et al (2013) Transurethral coagulation for radiation-induced hemorrhagic cystitis using Greenlight TM potassium-titanyl-phosphate laser. Photomed Laser Surg 31:78–81. https://doi.org/10.1089/pho.2012.3396 Zhang N, Yao D-W, Liu X-J, et al (2021) Outcome of a 980-nm diode laser coagulation in women with radiation-induced hemorrhagic cystitis: a single-center retrospective study. Lasers Med Sci 36:67–73. https://doi.org/10.1007/s10103-020-03005-2 Buonacera A, Stancanelli B, Colaci M, Malatino L (2022) Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases. Int J Mol Sci 23:3636. https://doi.org/10.3390/ijms23073636 Firment J, Hulin I (2024) Zahorec index or Neutrophil-to-lymphocyte ratio, valid biomarker of inflammation and immune response to infection, cancer and surgery. Bratisl Lek Listy 125:75–83. https://doi.org/10.4149/BLL_2024_012 Yue W, Liu Y, Jiang W, et al (2021) Prealbumin and D-dimer as Prognostic Indicators for Rebleeding in Patients with Nonvariceal Upper Gastrointestinal Bleeding. Dig Dis Sci 66:1949–1956. https://doi.org/10.1007/s10620-020-06420-1 Xiao Z, Mao X, Wang B, et al (2025) Relationship between high levels of D-dimer and prognosis in patients with spontaneous supratentorial cerebral haemorrhage: A retrospective study and double validation. J Stroke Cerebrovasc Dis 34:108129. https://doi.org/10.1016/j.jstrokecerebrovasdis.2024.108129 Tables Tables 1 to 3 are available in the Supplementary Files section Additional Declarations No competing interests reported. Supplementary Files Tables.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6495700","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":453744112,"identity":"e6f88387-3272-46f6-b9fb-ad0bef4c08ab","order_by":0,"name":"Lizhe An","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAqUlEQVRIiWNgGAWjYFCCBMYDDBUScvykaGE4wHDGwliygSQtjG0ViRuI1sJ3PPnBwZ/zJBg3MDA/fHSDGC2SZ54ZHJDcJsFszsBmbJxDjBaDGwkGBwy3SbBZNvCwSROpJf3DgcQ5EjwGB4jXkmNw4GCDhATxWiTPvCk42HBMwkCymVi/8B1P3/jwR01dfT9788PHRGkBxiMUMBOlHEXLKBgFo2AUjAJcAAAETTTvvWvcxwAAAABJRU5ErkJggg==","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Lizhe","middleName":"","lastName":"An","suffix":""},{"id":453744114,"identity":"cff69f7e-43f5-4ecf-90cf-762aca656d97","order_by":1,"name":"Yang Hong","email":"","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Hong","suffix":""},{"id":453744116,"identity":"1b5e8031-4a79-4966-a07c-dc99a8080da8","order_by":2,"name":"Luping Yu","email":"","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Luping","middleName":"","lastName":"Yu","suffix":""},{"id":453744117,"identity":"9da18898-9e5d-42ba-9bec-8c707a495c2c","order_by":3,"name":"Tao Xu","email":"","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Xu","suffix":""},{"id":453744119,"identity":"0b0fc5b2-7934-4214-915d-7acd40389d21","order_by":4,"name":"Jun Kong","email":"","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Kong","suffix":""}],"badges":[],"createdAt":"2025-04-21 11:38:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6495700/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6495700/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82561410,"identity":"42b5e1f3-2f40-41b3-a6cf-01da58aeb25c","added_by":"auto","created_at":"2025-05-13 01:38:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":499589,"visible":true,"origin":"","legend":"\u003cp\u003eA 10F suction catheter connected to vacuum was introduced through the sheath to aspirate and break down larger clots.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6495700/v1/9bd7d18c8417f14af46e77be.png"},{"id":82562602,"identity":"4c1f8527-b26f-4199-86bb-2003963d19dd","added_by":"auto","created_at":"2025-05-13 01:46:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":428954,"visible":true,"origin":"","legend":"\u003cp\u003eBleeding lesions of bladder mucosa were coagulated by electrical loop.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6495700/v1/2859a9157f84410dcc048a21.png"},{"id":82561368,"identity":"b1410f6a-9e7c-477c-89a6-fbfd6384f431","added_by":"auto","created_at":"2025-05-13 01:38:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":390958,"visible":true,"origin":"","legend":"\u003cp\u003eA: Endoscopic view was clear after clots removal and electrocoagulation, bleeding lesions were diffusely distributed in left and anterior walls, leaving normal mucosa in posterior and right walls. B: Left ureteral orifice was kept intact (white arrow).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6495700/v1/6126dc1e83c06e19fd2b5657.png"},{"id":82561376,"identity":"36250b71-8cec-4226-b273-3b3bca382dda","added_by":"auto","created_at":"2025-05-13 01:38:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":99540,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment flowchart of severe HC.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6495700/v1/f3add31be5f941f4027d3fbd.png"},{"id":82561377,"identity":"2e34c7fa-2f9a-41b4-8f82-9ac9d4bfb2e8","added_by":"auto","created_at":"2025-05-13 01:38:29","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":34485,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve of preoperative neutrophil-to-lymphocyte ratio (NLR) for predicting non-complete remission. The area under the curve (AUC) was 0.718. The optimal cutoff value was 4.555, which yielded a sensitivity of 71.4% and a specificity of 72.4% (Youden index = 0.438).\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-6495700/v1/d20791ddaf900225502a83cd.png"},{"id":95529935,"identity":"5af7d351-c3b8-4f1e-aac3-e105c6a0e2ae","added_by":"auto","created_at":"2025-11-10 10:17:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2499564,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6495700/v1/28f6d09c-1ab8-49bc-adee-22d6e7d47f44.pdf"},{"id":82561384,"identity":"1f538e66-2632-48dd-8045-864649282be4","added_by":"auto","created_at":"2025-05-13 01:38:30","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":29580,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-6495700/v1/533b665c65f0110da4d96920.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Endoscopic management of severe hemorrhagic cystitis after HSCT: experience from a high-volume center in China","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eHemorrhagic cystitis (HC) is a frequent complication following allogeneic hematopoietic stem cell transplantation (Allo-HSCT), with an incidence ranging from 12.2% and 36.9% [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In severe cases, HC may result in bladder tamponade, progressive hemoglobin decline, and hemodynamic instability, requiring urgent surgical intervention. Endoscopic clot evacuation and mucosal coagulation remain the mainstay of treatment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, thrombocytopenia, coagulopathy, and leukopenia are common in post-transplant patients, often accompanied by rapid and profuse hematuria, making endoscopic management particularly challenging.\u003c/p\u003e \u003cp\u003eAlthough severe HC is clinically significant, existing studies on endoscopic management after Allo-HSCT are limited, with small sample sizes and insufficient characterization of cystoscopic findings, surgical techniques, and prognostic factors [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe conducted a retrospective study of patients with severe HC who underwent endoscopic treatment at a high-volume hematology center in China. Endoscopic features were systematically described and used to grade the severity of HC. A \u0026ldquo;cyclical\u0026rdquo; technique combining suction, coagulation and irrigation was employed in cases with extensive bleeding and clot burden. Prognostic analysis was performed to identify factors associated with non-complete remission. To our knowledge, this study represents the largest single-center cohort to date on endoscopic treatment of HC after Allo-HSCT and provides detailed insight into intraoperative findings, surgical techniques, and outcome-related risk factors.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Clinical data\u003c/h2\u003e \u003cp\u003eThe medical records of patients who underwent Allo-HSCT at our center between January 2014 and December 2023 were retrospectively reviewed. Patients who developed severe HC and received endoscopic treatment were included. Severe HC was defined as gross hematuria refractory to conservative measures, accompanied by bladder tamponade or a rapid decline in hemoglobin requiring urgent intervention.\u003c/p\u003e \u003cp\u003eDemographic characteristics, transplantation-related variables, preoperative laboratory findings (including inflammatory, coagulation, renal function, and infectious parameters), imaging results, and endoscopic features were collected.\u003c/p\u003e \u003cp\u003eSurgical outcomes were classified as complete remission, partial remission, or no remission. Complete remission was defined as the complete resolution of gross hematuria; partial remission as persistent hematuria not requiring further invasive treatment; and no remission as requiring reoperation or other invasive interventions. Patients under 18 years, those with incomplete records, or those who did not undergo surgery due to contraindications were excluded. The study was approved by the Ethics Committee of Peking University People's Hospital (No. 2024PHB170-001).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Surgical techniques\u003c/h2\u003e \u003cp\u003eUnder general anesthesia, patients were positioned in lithotomy. A resectoscope (26F sheath) was introduced transurethrally to assess mucosal bleeding and clot size. HC was classified into three grades based on cystoscopic findings. Grade I, with no clots, allowed for immediate electrocoagulation and was the least complex. Grade II, with small number of clots, clots were removed via resection loop or washed out by Ellik bladder evacuator before electrocoagulation. Grade III, with extensive clots filled with bladder, was the most complex and required a \"cyclical\" technique to balance hemostasis and clot removal.\u003c/p\u003e \u003cp\u003eThe main steps for the \"cyclical\" technique are as follows. The scope is withdrawn, leaving the sheath in place. A 10F suction catheter connected to vacuum is then introduced through the sheath to aspirate and break down larger clots (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), while smaller clots are flushed out using Ellik bladder evacuator. Given the fragile bladder mucosa in HC patients, gentle handling is crucial when using Ellik bladder evacuator to avoid bladder rupture due to excessive irrigation pressure. After partial clot removal, the scope is reinserted, and electrocoagulation is applied to visible bleeding lesions while avoiding damage to the ureteral orifices (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Bladder tissue found in the flushed clots is sent for pathological examination. Clots removal and electrocoagulation are alternated until bleeding is controlled, indicated by a clear endoscopic view (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) and clear or light red irrigation fluid. Bladder mucosa is preserved as much as possible while ensuring effective hemostasis. Any remaining clots are removed using Ellik bladder evacuator or resection loop. Finally, a three-way Foley catheter is placed for continuous bladder irrigation.\u003c/p\u003e \u003cp\u003ePatients stayed in the hematology ward for continued care. Bladder irrigation stopped after three days of clear fluid, and the catheter was removed after seven days without bleeding. If bleeding worsened, repeat endoscopic hemostasis was performed. See Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e for the treatment flowchart.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Statistics\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using SPSS version 30.0. Continuous variables were tested for normality using the Shapiro\u0026ndash;Wilk test. Data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (interquartile range), and compared using the independent samples t-test or the Mann\u0026ndash;Whitney U test, as appropriate. Categorical variables were compared using the chi-square test or Fisher\u0026rsquo;s exact test. Variables with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in univariate analysis were included in a multivariate logistic regression model. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of selected variables. A two-sided P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 Patient characteristics and endoscopic features\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBetween January 2014 and December 2023, a total of 6,836 patients underwent allogeneic hematopoietic stem cell transplantation Allo-HSCT at our center. HC occurred in 1,668 patients (24.4%), of whom 69 (1.0%) developed severe HC as defined in this study, accounting for 4.1% of all HC cases. Fifty patients who received endoscopic treatment for severe HC were included in the final analysis.\u003c/p\u003e\n\u003cp\u003eThe median age was 32.5 years (IQR 23\u0026ndash;44), and 56% were male. The most common primary hematologic diseases were acute lymphoblastic leukemia (48%) and acute myeloid leukemia (22%). The median onset of HC was 31 days (IQR 22\u0026ndash;45) after transplantation, with a median duration of 61 days (IQR 35\u0026ndash;89). Viral infection was the most frequently suspected cause (64%). The primary indications for surgery were progressive hemoglobin decline (58%), bladder tamponade (8%), or both (34%). Most patients (92%) required perioperative blood transfusion.\u003c/p\u003e\n\u003cp\u003eThe median operative time was 55 minutes (IQR 40\u0026ndash;95). On cystoscopy, 64% of patients had grade III HC. Bladder mucosal involvement exceeded 50% in 84% of cases, and the bladder trigone was involved in 16%. Lesions were most commonly located on the posterior wall (58%), anterior wall (52%), right wall (50%), left wall (40%), and dome (40%).\u003c/p\u003e\n\u003cp\u003eAmong the 50 patients, complete remission was achieved in 29 (58%), partial remission in 14 (28%), and no remission in 7 (14%). Detailed clinical characteristics are summarized in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Comparison of clinical parameters between complete and non-complete remission groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were divided into two groups based on surgical outcomes: complete remission (n = 29) and non-complete remission (n = 21). As shown in Table 2, no significant differences were observed between the two groups in terms of age, sex, primary hematologic disease, onset or duration of HC, or most routine laboratory parameters.\u003c/p\u003e\n\u003cp\u003eHowever, patients in the non-complete remission group had significantly higher preoperative neutrophil count (median 3.18 vs. 2.19 \u0026times;10⁹/L, P = 0.046), neutrophil-to-lymphocyte ratio (NLR) (median 6.51 vs. 3.14, P = 0.009), and D-dimer levels (median 436 vs. 263.5 ng/mL, P = 0.041).\u003c/p\u003e\n\u003cp\u003eRegarding endoscopic and imaging findings, hydronephrosis was more common in the non-complete remission group (47.6% vs. 10.3%, P = 0.003). In addition, patients in this group had a significantly higher rate of grade III HC (71.4% vs. 41.4%, P = 0.035) and bladder trigone involvement (28.6% vs. 6.9%, P = 0.048). There were no significant differences in operative time and extent of mucosal involvement. Detailed comparisons are summarized in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Multivariate analysis of risk factors for non-complete remission\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMultivariate logistic regression was conducted to identify independent predictors of non-complete remission. As shown in Table 3, hydronephrosis (odds ratio [OR] = 11.07, 95% confidence interval [CI]: 1.87\u0026ndash;65.56, P = 0.008) and involvement of the bladder trigone (OR = 10.69, 95% CI: 1.07\u0026ndash;106.61, P = 0.043) were independently associated with an increased risk of non-complete remission.\u003c/p\u003e\n\u003cp\u003eAlthough the neutrophil-to-lymphocyte ratio (NLR) showed a trend toward significance (OR = 1.206, 95% CI: 0.988\u0026ndash;1.472, P = 0.065), it did not meet the statistical threshold. Other variables, including neutrophil count (OR = 0.959, P = 0.787), D-dimer (OR = 1.001, P = 0.119), and endoscopic grade of HC (grade III vs. I\u0026ndash;II: OR = 3.579, P = 0.109), were not independently associated with treatment outcome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4 Predictive value of NLR for surgical outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eReceiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of preoperative NLR for non-complete remission. The area under the curve (AUC) was 0.718 (95% CI: 0.581\u0026ndash;0.854, P = 0.012), indicating moderate discriminative ability. The optimal cutoff value of NLR was 4.555, which yielded a sensitivity of 71.4% and a specificity of 72.4% (Figure 5).\u003c/p\u003e"},{"header":"4. Discussions","content":"\u003cp\u003eThe incidence of HC after Allo-HSCT was reported 12.2% and 36.9% [1]. According to large sample data of our center, the incidence was 24.1%, with 1% developing severe HC, highlighting the need for timely intervention.\u003c/p\u003e\n\u003cp\u003eConservative treatments such as hydration and bladder irrigation are suitable for mild cases [6].\u0026nbsp;Intravesical agents and hyperbaric oxygen therapy have been reported but are limited by delayed efficacy and poor accessibility [7, 8]. Endoscopic management is the preferred approach for severe HC requiring timely hemostasis, while cystectomy is reserved for refractory cases due to its invasiveness [4]. Most existing studies focus on radiation-induced HC [9, 10], and data on Allo-HSCT-related HC remain limited. This study presents the largest cohort to date on endoscopic management of HC after Allo-HSCT, with characterization of endoscopic findings, surgical techniques, and associated prognostic factors.\u003c/p\u003e\n\u003cp\u003eSevere cases were often marked by heavy bleeding and poor visibility. Traditional methods, such as Ellik evacuators and ultrasonic probes, were ineffective. We adopted a \u0026ldquo;cyclical\u0026rdquo; technique using vacuum-assisted suction for clot removal, followed by electrocoagulation. This approach enabled efficient hemostasis, with a median operative time of 108 minutes in Grade III cases.\u003c/p\u003e\n\u003cp\u003eGiven that 28% of patients achieved only partial remission and 14% had no remission after endoscopic treatment, early identification of high-risk individuals is essential to guide postoperative management. Therefore, we analyzed clinical and endoscopic factors associated with surgical outcomes by comparing patients with complete and non-complete remission.\u003c/p\u003e\n\u003cp\u003eSignificant differences were observed in preoperative neutrophil-to-lymphocyte ratio, D-dimer levels, hydronephrosis, and bladder trigone involvement. NLR is a marker of systemic inflammation that reflects the balance between inflammation and immunity, and has shown prognostic value in various inflammatory conditions [11, 12]. In our study, elevated preoperative NLR was associated with poor surgical outcomes, possibly reflecting a more intense inflammatory response within the bladder mucosa. Similarly, elevated D-dimer level was also linked to poor prognosis. D-dimer is a fibrin degradation product that reflects activation of coagulation and fibrinolysis, and has been associated with adverse outcomes in conditions such as gastrointestinal and intracerebral hemorrhage [13, 14]. Its elevation in severe HC may indicate greater mucosa injury or ongoing bleeding. Unlike radiation-induced cystitis [10], which typically affects the bladder trigone due to localized pelvic exposure, trigone involvement was relatively uncommon in HC after Allo-HSCT, likely due to its viral-mediated pathogenesis. However, when present\u0026mdash;especially alongside hydronephrosis\u0026mdash;it often indicated extensive urothelial involvement and was associated with worse prognosis.\u003c/p\u003e\n\u003cp\u003eIn addition to laboratory and imaging indicators, our study also highlighted the prognostic value of intraoperative findings. Patients with grade III hemorrhagic cystitis had significantly lower remission rates, underscoring the importance of endoscopic assessment in guiding management and predicting outcomes. Consistent with these observations, multivariate logistic regression confirmed both trigone involvement and hydronephrosis as independent risk factors for non-complete remission (Table 3).\u003c/p\u003e\n\u003cp\u003eAlthough NLR did not reach statistical significance in multivariate analysis, given its clinical relevance and a p-value near the significance threshold, we performed ROC analysis to further evaluate its predictive utility. The resulting AUC of 0.718 suggests moderate discriminative ability, and the identified cutoff value of 4.555 may provide a useful reference for preoperative risk stratification in clinical settings (Figure 5).\u003c/p\u003e\n\u003cp\u003eOur study had several limitations. Firstly, it was a single-center retrospective analysis; however, as one of the largest hematology centers in China, the sample size is sufficient. Secondly, electrocoagulation was the only method employed for hemostasis, lacking a comparison with laser or other energy platforms. Lastly, while this study focused on short-term outcomes, it lacked long-term follow-up data, which is essential for evaluating postoperative bladder function.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThis single-center study presents the largest cohort to date on endoscopic management of severe HC after Allo-HSCT. A “cyclical” technique was developed to improve efficiency of clot removal and hemostasis under poor endoscopic visibility. An endoscopic grading system was established to reflect intraoperative complexity, and higher grades were associated with worse outcomes. Prognostic analysis further identified hydronephrosis and trigone involvement as independent risk factors, while preoperative NLR demonstrated moderate predictive value for surgical response. These findings may support risk-adapted surgical and postoperative strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u003c/strong\u003e None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor(s) Participation:\u0026nbsp;\u003c/strong\u003eLZ An: Data collection and Manuscript writing. Y Hong: Data collection. LP Yu: Data management. T Xu: Project development. J Kong: Project development and manuscript editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eGalli E, Metafuni E, Gandi C, et al (2024) Risk factors for hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation in a letermovir-exposed CMV-free population receiving PTCy. Eur J Haematol 112:577\u0026ndash;584. https://doi.org/10.1111/ejh.14147\u003c/li\u003e\n \u003cli\u003eTirindelli MC, Flammia GP, Bove P, et al (2014) Fibrin glue therapy for severe hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 20:1612\u0026ndash;1617. https://doi.org/10.1016/j.bbmt.2014.06.018\u003c/li\u003e\n \u003cli\u003eSakurada M, Kondo T, Umeda M, et al (2016) Successful treatment with intravesical cidofovir for virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A case report and a review of the literature. J Infect Chemother 22:495\u0026ndash;500. https://doi.org/10.1016/j.jiac.2016.01.013\u003c/li\u003e\n \u003cli\u003eHayashida M, Nishida A, Kuno M, et al (2024) Novel Insights into Predictors, Optimized Treatments, and Prognosis Factors for Virus-Induced Hemorrhagic Cystitis Post-Hematopoietic Stem Cell Transplantation: A Single-Institution Study of 427 Japanese Patients. Blood 144:2162\u0026ndash;2162. https://doi.org/10.1182/blood-2024-199936\u003c/li\u003e\n \u003cli\u003eTang FF, Zhang XH, Chen H, et al (2017) [Surgical treatment of severe, refractory hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation: a report of 17 patients]. Zhonghua Nei Ke Za Zhi 56:414\u0026ndash;418. https://doi.org/10.3760/cma.j.issn.0578-1426.2017.06.006\u003c/li\u003e\n \u003cli\u003eYang W-B, Du Y-Q, Bai W-J, et al (2021) Multivariate analysis of factors predicting surgical intervention for hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Chin Med J (Engl) 134:1480\u0026ndash;1482. https://doi.org/10.1097/CM9.0000000000001295\u003c/li\u003e\n \u003cli\u003eYozgat AK, Bozkaya IO, Aksu T, et al (2022) Analysis of Hemorrhagic Cystitis and BK Viremia in Children after Hematopoietic Stem Cell Transplantation. Indian J Transplant 16:174. https://doi.org/10.4103/ijot.ijot_84_21\u003c/li\u003e\n \u003cli\u003eJiang Y, Chen H, Fang X, et al (2020) Hyperbaric Oxygen Therapy for Late-Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation and Effective Factors Prediction. Blood 136:27\u0026ndash;28. https://doi.org/10.1182/blood-2020-136891\u003c/li\u003e\n \u003cli\u003eZhu J, Xue B, Shan Y, et al (2013) Transurethral coagulation for radiation-induced hemorrhagic cystitis using Greenlight\u003csup\u003eTM\u003c/sup\u003e potassium-titanyl-phosphate laser. Photomed Laser Surg 31:78\u0026ndash;81. https://doi.org/10.1089/pho.2012.3396\u003c/li\u003e\n \u003cli\u003eZhang N, Yao D-W, Liu X-J, et al (2021) Outcome of a 980-nm diode laser coagulation in women with radiation-induced hemorrhagic cystitis: a single-center retrospective study. Lasers Med Sci 36:67\u0026ndash;73. https://doi.org/10.1007/s10103-020-03005-2\u003c/li\u003e\n \u003cli\u003eBuonacera A, Stancanelli B, Colaci M, Malatino L (2022) Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases. Int J Mol Sci 23:3636. https://doi.org/10.3390/ijms23073636\u003c/li\u003e\n \u003cli\u003eFirment J, Hulin I (2024) Zahorec index or Neutrophil-to-lymphocyte ratio, valid biomarker of inflammation and immune response to infection, cancer and surgery. Bratisl Lek Listy 125:75\u0026ndash;83. https://doi.org/10.4149/BLL_2024_012\u003c/li\u003e\n \u003cli\u003eYue W, Liu Y, Jiang W, et al (2021) Prealbumin and D-dimer as Prognostic Indicators for Rebleeding in Patients with Nonvariceal Upper Gastrointestinal Bleeding. Dig Dis Sci 66:1949\u0026ndash;1956. https://doi.org/10.1007/s10620-020-06420-1\u003c/li\u003e\n \u003cli\u003eXiao Z, Mao X, Wang B, et al (2025) Relationship between high levels of D-dimer and prognosis in patients with spontaneous supratentorial cerebral haemorrhage: A retrospective study and double validation. J Stroke Cerebrovasc Dis 34:108129. https://doi.org/10.1016/j.jstrokecerebrovasdis.2024.108129\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Allogeneic hematopoietic stem cell transplantation, Hemorrhagic cystitis, Endoscopic, Surgical techniques, Prognostic factors","lastPublishedDoi":"10.21203/rs.3.rs-6495700/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6495700/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective: To describe endoscopic features, surgical techniques, and prognostic factors of severe hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), based on experience from a high-volume center in China.\u003c/p\u003e\n\u003cp\u003eMethods: A retrospective analysis was conducted of 50 patients with severe HC who underwent endoscopic electrocautery from 2014 to 2023. Severe HC was defined as requiring urgent intervention after failed conservative management and was classified into three endoscopic grades based on the burden of blood clots. Grade III cases were treated using a “cyclical” technique. Patients were grouped by surgical outcomes for comparison.\u003c/p\u003e\n\u003cp\u003eResults: Among 50 patients (56% male; median age 32.5 years), the median onset of HC was 31 days after Allo-HSCT, and the preoperative duration was 61 days. Endoscopy revealed grade III HC in 64%, extensive bladder mucosal involvement in 84%, and trigone involvement in 16%. Lesions commonly involved the posterior and anterior walls. The median operative time was 55 minutes. Complete remission was achieved in 58% of patients. Compared with the complete group, the non-complete group had higher neutrophil-to-lymphocyte ratio (NLR), D-dimer, and more frequent hydronephrosis and trigone involvement. Hydronephrosis and trigone involvement independently predict poor outcomes, and preoperative NLR has moderate predictive value (AUC = 0.718; cutoff = 4.555).\u003c/p\u003e\n\u003cp\u003eConclusion: Severe HC after Allo-HSCT requires timely endoscopic intervention. Most cases present as grade III and can be effectively managed using the “cyclical”technique. Hydronephrosis and trigone involvement are independent risk factors for poor outcomes, and preoperative NLR has moderate predictive value.\u003c/p\u003e","manuscriptTitle":"Endoscopic management of severe hemorrhagic cystitis after HSCT: experience from a high-volume center in China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 01:38:19","doi":"10.21203/rs.3.rs-6495700/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"06e58bd1-bb38-41bd-bf14-7852b6aaed90","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-10T08:09:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-13 01:38:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6495700","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6495700","identity":"rs-6495700","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}