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1.
Risk factors for hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation in a letermovir-exposed CMV-free population receiving PTCy
Galli, E., Metafuni, E., Gandi, C., Limongiello, M. A., Giammarco, S., Mattozzi, A., Santangelo, R., Bacigalupo, A., Sorà, F., Chiusolo, P., et al
European journal of haematology. 2024
Abstract
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.
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2.
Analysis of early clinical signs and risk factors for severe hemorrhagic cystitis after stem cell transplantation in children
Liu, P., Bai, K., Zhang, Z., Sun, J.
International journal of urology : official journal of the Japanese Urological Association. 2024
Abstract
INTRODUCTION To analyze the characteristics of early clinical symptoms of hemorrhagic cystitis (HC) after hematopoietic stem cell transplantation (HSCT) and the risk factors of severe HC. METHODS We retrospectively analyzed 77 children with post-HSCT HC treated at our hospital between June 2013 and June 2021. Clinical characteristics were collected and catalogued. RESULTS Among the children with urinary tract irritation symptoms (UTIS) as the first symptom, symptoms appeared earlier than hematuria symptoms (28 day vs. 31 day, p = 0.027), and the time progressing to severe HC was significantly longer in these children (12 day vs. 7 day, p = 0.038), but there was no significant difference in the number of participants (57.8% vs. 59.4%, p = 0.889). BK polyomavirus (BKV) infection was an independent risk factor (hazard ratio [HR] = 2.782, p = 0.035) for severe HC, which was also positively associated with multi-viral infection (HR = 2.215, p = 0.020). CONCLUSIONS In HC children, when the first urinary tract symptom was UTIS, it appeared earlier than hematuria, and the time of progression to severe HC was significantly longer, suggesting that we still need more aggressive treatment for these children to prevent the worsening of symptoms. The severity of HC was positively correlated with BKV infection and multiple infections.
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3.
[Risk Factors of Late-Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation]
Zhang, L. Y., Xiong, Y. Y., Liao, M. Y., Xiao, Q., Tang, X. Q., Luo, X. H., Zhang, H. B., Wang, L., Liu, L.
Zhongguo shi yan xue ye xue za zhi. 2024;32(1):250-256
Abstract
To analyze the risk factors for late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the risk factors for the progression of LOHC to severe LOHC, and the effect of LOHC on survival. METHODS The clinical data of 300 patients who underwent allo-HSCT at the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2021 were retrospectively analyzed. The relevant clinical parameters that may affect the occurance of LOHC after allo-HSCT were selected for univariate and multivariate analysis. Then, the differences in overall survival (OS) and progression-free survival (PFS) between different groups were analyzed. RESULTS The results of multivariate analysis showed that the independent risk factors for LOHC after allo-HSCT were as follows: age≤45 years old (P =0.039), intensified conditioning regimen with fludarabine/cladribine and cytarabine (P =0.002), albumin≤30 g/L on d30 after transplantation (P =0.007), CMV-DNA positive (P =0.028), fungal infection before transplantation (P =0.026), and the occurrence of grade Ⅱ - Ⅳ aGVHD (P =0.006). In the transplant patients who have already developed LOHC, the occurance of LOHC within 32 days after transplantation (P =0.008) and albumin≤30 g/L on d30 after transplantation (P =0.032) were independent risk factors for the progression to severe LOHC. The OS rate of patients with severe LOHC was significantly lower than that of patients without LOHC (P =0.041). CONCLUSION For the patients aged≤45 years old and with intensified conditioning regimen, it is necessary to be vigilant about the occurrence of LOHC; For the patients with earlier occurrence of LOHC, it is necessary to be vigilant that it develops into severe LOHC. Early prevention and treatment of LOHC are essential. Regular monitoring of CMV-DNA and albumin levels, highly effective antiviral and antifungal therapies, and prevention of aGVHD are effective measures to prevent the occurrence and development of LOHC.
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4.
Risk factors for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis
Zhou, X., Zhang, S., Fan, J., Zhu, X., Hu, S.
Clinical transplantation. 2023;:e15121
Abstract
OBJECTIVE AND BACKGROUND BK virus-associated hemorrhagic cystitis (BKV-HC) is an intractable complication leading to higher mortality and prolonged hospitalization among allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients. Therefore, identifying the potential risk factors of BKV-HC after allo-HCT is crucial to improve prognosis and for early prevention. However, the risk factors for BKV-HC remain debatable. Therefore, we conducted a systematic review and meta-analysis to identify the risk factors for BKV-HC, for early prevention of the occurrence of BKV-HC and to improve the quality of life and prognosis of allo-HCT recipients. METHODS We searched relevant studies from PubMed, EMBASE, and the Cochrane Library up to February 2023. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of all risk factors were calculated to evaluate their effects on the occurrence of BKV-HC. RESULTS Overall, 11 studies involving 2556 allo-HCT recipients were included in this meta-analysis. All included studies were retrospective and published between 2013 and 2022. We found that male sex (OR = 1.32; 95% CI, 1.07-1.62; p = .009, I(2) = 34%), haploidentical donor (OR = 1.84; 95% CI, 1.18-2.87; p = .007, I(2) = 23%), myeloablative conditioning (OR = 1.76; 95% CI, 1.36-2.28; p < .0001, I(2) = 45%), acute graft versus host disease (aGVHD) (OR = 2.73; 95% CI, 2.02-3.69; p < .0001, I(2) = 46%), chronic graft versus host disease (cGVHD) (OR = 1.71; 95% CI, 1.12-2.60; p = .01, I(2) = 0%), and cytomegalovirus (CMV) reactivation (OR = 3.13; 95% CI, 1.12-8.78; p = .03, I(2) = 79%) were significantly associated with BKV-HC in the univariable analysis. CONCLUSIONS Our meta-analysis indicated that male sex, haploidentical donor, myeloablative conditioning, aGVHD, cGVHD, and CMV reactivation were potential risk factors for BKV-HC.
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5.
Decreased lymphocyte count before conditioning is associated with BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation
Xie, X. T., Zhang, Y. F., Zhang, Y., Zeng, H. Q., Deng, J. C., Zhou, K., Chen, L., Luo, Y., Lou, S. F.
International immunopharmacology. 2023;121:110515
Abstract
BACKGROUND BK virus-associated hemorrhagic cystitis (BKV-HC) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It can cause morbidity and may increase treatment-related mortality. Previous studies showed that the occurrence of BKV-HC was related to various factors. However, there are still many controversial factors. It is not clear whether BKV-HC will affect the long-term prognosis of patients. OBJECTIVE We aimed to identify risk factors for BKV-HC after allo-HSCT and evaluate the effect of BKV-HC on overall survival (OS) and progression- free survival (PFS) of patients. STUDY DESIGN We retrospectively analyzed the clinical data of 93 patients who underwent allo-HSCT. Univariate and multivariate analysis were used to identify risk factors for BKV-HC. The Kaplan-Meier method was used to estimate OS and PFS. A difference was considered statistically significant if P < 0.05. RESULTS A total of 24 patients developed BKV-HC. The median occurrence time of BKV-HC was 30 (range:8-89) days after transplantation, and the median duration was 25.5 (range:6-50) days. Multivariate logistic regression analysis indicated that peripheral blood lymphocyte count <1 × 10(9)/L before conditioning (OR = 4.705, P = 0.007) and haploidentical transplantation (OR = 13.161, P = 0.018) were independent risk factors for BKV-HC. The 3-year OS rate was 85.9% (95%CI:62.1%-95.2%) in the BKV-HC group and 73.1% (95%CI: 58.2%-88.0%) in the non-BKV-HC group. There was no significant difference between the two groups (P = 0.516). The 3-year PFS rate was 76.3% (95%CI: 57.9%-94.7%) in the BKV-HC group and 58.1% (95%CI: 39.5%-76.7%) in the non-BKV-HC group. There was no significant difference in the two groups (P = 0.459). The severity of BKV-HC was not related to the OS and PFS of the patients (P value was 0.816 and 0.501, respectively). CONCLUSION Haploidentical transplantation and decreased peripheral blood lymphocyte count before conditioning increased the risk of BKV-HC after allo-HSCT. The occurrence of BKV-HC after allo-HSCT and the severity of which did not affect OS and PFS of the patients.
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6.
BK Virus Infections and Hemorrhagic Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients
Sökmen, H., Öztürk, G., Çimentepe, M., Özen, S., Wahhab Alantake, H. A., Bayram, İ, Yarkın, F.
The new microbiologica. 2023;46(2):141-145
Abstract
BK virus (BKV) associated with hemorrhagic cystitis (HC) is the most important complication that develops after hematopoietic stem cell transplantation (HSCT) in patients with hematological malignancies. This study aims to investigate BKV infections and HC in pediatric patients after allogeneic hematopoietic stem cell transplantation. Between November 2018 and November 2019, a total of 51 patients between the ages of 11 months and 17 years were included in the study. BKV Bosphore ® v1 quantification kit (Geneworks Anatolia, Turkey) was used for the detection of BKV DNA in urine and blood samples. Among the total of 51 patients, the incidence of BKV infection was found to be 86.3%. Allogeneic HSCT was performed in 40 patients and autologous HSCT in 11 patients. BK viruria and/or viremia were detected in 85% (44) of patients who underwent allogeneic HSCT and in 90% in the autologous group. High-level BK viruria (>107 copies/mL) was found in 41% (9) of 22 patients who were BKV positive before transplantation, while in 27.5% (8) of 29 patients who were BKV negative before transplantation; thus, BKV positivity before transplantation was considered a risk factor for high-level BK viruria. Acute GVHD developed in 6 of 40 patients in the allogeneic group. HC was prevented in 12 (67%) of 18 patients who received preemptive treatment, while HC developed in 6 (33%). HC occurred at a median of 35 days (17-49 days) post-transplant. Despite preemptive treatment, 6 (15%) patients who developed HC associated with BKV were in the allogeneic group but not in the autologous group. Of these patients with HC, 5 received a myeloablative treatment regimen, and 1 patient was given a reduced-intensity treatment regimen. The viral load in urine was found to be 107-9 copies/mL within 2 weeks before the development of HC and has been identified as a prognostic indicator. In conclusion, early diagnosis of viral infections by monitoring BKV viral load in HSCT patients will be effective in preventing the progression of complications such as BKV-associated HC by providing timely initiation of preemptive treatment.
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7.
BK Polyomavirus Diversity After Hematopoietic Stem Cell Transplantation
Odegard, E. A., Meeds, H. L., Kleiboeker, S. B., Ziady, A., Sabulski, A., Jodele, S., Seif, A. E., Davies, S. M., Laskin, B. L., Blackard, J. T.
The Journal of infectious diseases. 2023
Abstract
BK polyomavirus (BKPyV) infection is common after hematopoietic stem cell transplantation (HSCT) and is associated with the development of hemorrhagic cystitis (HC). The role that BKPyV plays in the pathogenesis of HC is not well characterized. We investigated the impact of BKPyV diversity on the development of HC using a previously established cohort of pediatric HSCT patients. There were 147 urine samples with quantifiable BKPyV at month 1 after HSCT; 137 (93.2%) were amplified using our in-house polymerase chain reaction approach and sent for next-generation sequencing. Subtype Ia was most frequent (61.3%), followed by subtype Ib1 (31.4%). The median viral load of subtype Ia samples was higher than for subtype Ib1 at month 1. Across the protein coding regions, APOBEC-induced mutations and signature patterns associated with HC were identified. This is the largest sequencing study of a single cohort of HSCT patients, providing a vast resource of sequence data for future analyses.
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8.
Hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation: experience in a pediatric oncological institution
de la Puente, S., Espinoza, M. L., Carrillo, I., Rico, C., Souto, H., Acedo, J. A., Riñón, C., Garcés, C., Ramos, P., Muñoz, D., et al
Cirugia pediatrica : organo oficial de la Sociedad Espanola de Cirugia Pediatrica. 2023;36(3):128-134
Abstract
OBJECTIVE To analyze the risk factors associated with hemorrhagic cystitis (HC) severity and the treatment strategies available in HC patients following allogeneic hematopoietic stem cell transplantation (AHSCT). MATERIALS AND METHODS A retrospective study of medical records was carried out. Patients with HC following AHSCT treated from 2017 to 2021 were divided into two groups according to severity -mild and severe. Demographic data, disease-specific characteristics, urological sequelae, and overall mortality were compared between both groups. The hospital's protocol was used for patient management. RESULTS 33 episodes of HC were collected in 27 patients, 72.7% of whom were male. HC incidence following AHSCT was 23.4% (33/141). 51.5% of HCs were severe (grades III-IV). Severe graft host disease (GHD) (grades III-IV) and thrombopenia at HC onset were associated with severe HC (p= 0.043 and p= 0.039, respectively). This group had longer hematuria times (p< 0.001) and required more platelet transfusions (p= 0.003). In addition, 70.6% required bladder catheterization, but only 1 case needed percutaneous cystostomy. None of the patients with mild HC required catheterization. No differences were found in terms of urological sequelae or overall mortality. CONCLUSIONS Severe HC could be predicted thanks to the presence of severe GHD or thrombopenia at HC onset. Severe HC can be managed with bladder catheterization in most of these patients. A standardized protocol may help reduce the need for invasive procedures in patients with mild HC.
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9.
Interaction between High-Dose Intravenous Busulfan and Post-Transplant Cyclophosphamide on Hemorrhagic Cystitis after Allogeneic Hematopoietic Cell Transplantation
Carreira, A. S., Salas, M. Q., Remberger, M., Novitzky-Basso, I., Law, A. D., Lam, W., Pasic, I., Mazzulli, T., Cserti-Gazdewich, C., Kim, D. D. H., et al
Transplantation and cellular therapy. 2023
Abstract
This study investigates the incidence and predictors of hemorrhagic cystitis (HC) in 960 adults undergoing allo-HSCT. Two-hundred and fifty-two (26.5%) patients received MAC regimens, and 81.4% received high-dose IV busulfan (HD Bu). Six-hundred and ninety-five (72.4%) patients received PTCY-based prophylaxis, and 91.4% additionally received ATG and CsA (PTCY-ATG-CsA). 228 (23.8%) patients developed HC. The day +100 cumulative incidences of grades 2-4 and 3-4 HC were 11.1% and 4.9%. BK virus was isolated in 58.3% of urinary samples. Using HD BU myeloablative regimens increased the risk for grade 2-4 HC (HR 1.97, P=0.035), and HD BU combined with ATG-PTCY-CsA increased this four times (HR 4.06, HR<0.001) for grade 2-4 HC compared to patients who received neither of these drugs. A significant correlation was documented between grade II-IV aGVHD and grade 2-4 HC (HR 2.10, P<0.001). Moreover, patients with BK-POS grade 2-4 HC had lower 1-year OS (HR 1.51, P=0.009) and higher NRM (HR 2.31, P<0.001), and patients with BK-NEG grade 2-4 HC had comparable post-transplant outcomes. In conclusion, intravenous HD Bu was identified as a predictor for grade 2-4 HC. Moreover, when HD Bu was combined with PTCY-ATG-CsA, the risk increased four-fold. Based on the results provided by this study, preventing the onset of HC, especially in high-risk patients, is mandatory as its presence significantly increases the risk for mortality.
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10.
CMV infection is a risk factor for hemorrhagic cystitis after hematopoietic stem cell transplantation
Zhang, L., Khadka, B., Wu, J., Feng, Y., Long, B., Xiao, R., Liu, J.
Annals of hematology. 2023
Abstract
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 37 days (range - 5 to 98 days) 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.