Restrictive versus standard hyperhydration during high-dose cyclophosphamide for hematopoietic stem cell transplantation: a retrospective cohort study

Late-Onset Hemorrhagic Cystitis in Children after Hematopoietic Stem Cell Transplantation for Thalassemia and Sickle Cell Anemia: A Prospective Evaluation of Polyoma (BK) Virus Infection and Treatment with Cidofovir

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

Continuous Intravenous Injection Of Mesna Can Reduce Acute Hemorrhagic Cystitis Occurrence Rate In Hematopoietic Stem Cell Transplantation: 359 Allo-HSCT Cases Report

Risk Factors for BK Viruria and Hemorrhagic Cystitis in Hematopoietic Stem Cell Transplant (HSCT) Recipients.

Hemorrhagic cystitis (HC) is one of the common complications of hematopoietic stem cell transplantation (HSCT). And its clinical features are hematuria, accompanied by urinary frequency, urgency, urine pain and other bladder irritation symptoms. Early onset hemorrhagic cystitis (EOHC) mainly results from uroepithelial injury induced by irradiation/chemotherapy during conditioning regimen particularly high-dose cyclophosphamide. With the use of mesna, the incidence decreased significantly. Late onset hemorrhagic cystitis (LOHC) is usually associated with viral infection and immune dysfunction, but the treatment of LOHC remains a challenge. As the HSCT is extensively used, the researches on diagnosis and treatment of HC are increasing. This article reviews literatures on the etiology, pathogenesis, diagnosis and treatment of HC. Key words: Cystitis; Hematopoietic stem cell transplantation; Etiology

Fluid Overload Early after Allogeneic Hematopoietic Stem Cell Transplantation Was Associated with Poor Survival

Sequential Therapy Combining Clofarabine and HLA-Haploidentical Hematopoietic Stem Cell Transplantation In The Treatment Of Refractory and Advanced Lymphoma: Feasibility, Toxicity and Early Outcome

Objective To investigate the hemostatic effect of hemocoagulase in patients with hemorrhagic cystitis (HC) post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods From July 2010 to December 2015, 173 cases of patients with HC of grade Ⅰ-Ⅳ post-allo-HSCT in department of hematology, First Affiliated Hospital of Soochow University were included into this study. 93 cases of patients who received hemocoagulase for HC treatment were included into research group. 80 cases of patients who did not receive hemocoagulase were chose as control group. HC of grade Ⅰ, Ⅱ, Ⅲ and Ⅳ in research group included 28, 25, 20 and 20 cases, respectively. HC of grade Ⅰ, Ⅱ, Ⅲ and Ⅳ in control group included 20 cases, respectively. HC patients in control group received conventional treatment for HC: full hydration and alkalinization of urine, and treated with broad spectrum antiviral agents. Twenty cases of grade Ⅳ HC patients in control group received bilateral embolization of internal iliac artery under digital subtraction angiography (DSA) as the conventional treatment for HC failed, and then received conventional treatment for HC again until the hemorrhage stopped. HC patients in research group received intravenous infusion of hemocoagulase on the basis of conventional treatment for HC in control group. The dose of hemocoagulase in phase one was 1 U/d, and if the patients in research group had no allergic reaction after treated for the first time, and one day later the dosage in phase two could be added to one unit once or twice daily continuously for 3-7 days as a cycle. Six cases of grade Ⅳ HC patients in research group received bilateral embolization of internal iliac artery under DSA as the hemocoagulase treatment for HC failed, and then received hemocoagulase treatment for HC again until the hemorrhage stopped. According to the dosage of hemocoagulase in phase two, patients in research group were divided to 1 U/d subgroup (n=29) and 2 U/d subgroup (n=64). And according to the total dose of hemocoagulase in phase two, patients in research group were divided the total dose of hemocoagulase >6 U subgroup (n=62) and the total dose of hemocoagulase ≤6 U subgroup (n=31) again. The duration of HC, adverse effects and relapse rate were observed in each group. Platelet count and related coagulation indicators including prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (Fib) level were monitored before and after the application of hemocoagulase in research group and control group. Duration of HC in two groups, platelet count and related coagulation indicators before-hemocoagulase and post-hemocoagulase in four subgroups of research group were analyzed by statistical methods. There were no significant differences of the age, gender ratio, grade of HC, type of diseases and transplantation methods between two groups (P>0.05). The study protocol was approved by the Ethical Review Board of Investigation in the First Affiliated Hospital of Soochow University. Results ①The duration of HC in research group was (14.5±5.2) d, statistically shorter than (22.5±7.7) d in control group, and the difference was statistically significant (t=8.101, P=0.000). The duration of grade Ⅰ, Ⅱ and Ⅲ HC in research group were (9.7±4.5) d, (14.2±5.8) d and (23.4±8.6) d, respectively, and all were shorter than (17.3±8.6) d, (26.8±10.9) d, and (36.5±17.8) d, respectively in control group, and all the differences were statistically significant (t=3.949, 4.979, 2.967; P=0.000, 0.000, 0.004). Before receiving bilateral embolization of internal iliac artery under DSA, the duration of grade Ⅳ HC in research group and control group were (26.4±7.8) d and (28.0±10.9) d, respectively, and there was no statistical difference between them (P=0.597). Grade Ⅳ HC in research group and control group were invalid after hemacoagulase treatment or conventional treatment in the observation period and received bilateral interventional embolization of internal iliac artery under DSA. After the operation, the duration of grade Ⅳ HC in research group and control group were (6.7±1.6) d and (9.6±2.1) d, respectively, and the difference was statistically significant (t=4.912, P=0.000). ②In 1 U/d subgroup of research group, Fib level of post-hemocoagulase was (2.3±0.6) g/L, which was lower than that of before-hemocoagulase [(2.7±0.4) g/L], and the difference was statistically significant (t=2.987, P=0.004). But the PT, APTT and platelet count compared before-hemocoagulase and post-hemocoagulase, there were no statistical differences (P>0.05). In the 2 U/d subgroup, total dose of hemocoagulase >6 U subgroup and ≤6 U subgroup, Fib level and platelet count decreased significantly after treated with hemocoagulase, and all the differences were statistically significant (Fib level: t=7.710, 7.195, 2.490; P=0.000, 0.000, 0.016; platelet count: t=3.563, 5.179, 2.189; P=0.001, 0.000, 0.032). But the PT and APTT compared before-hemocoagulase and post-hemocoagulase in those three subgroups, there were no statistical differences (P>0.05). ③In research group, 3 cases of patients occured kidney functional lesion and 8 cases of patients occurred graft-versus-host disease (GVHD); while in control group, 2 cases of patients occurred kidney functional lesion, 4 cases of patients occurred GVHD and 3 cases of patients occurred drug-induced liver injury. All the adverse reactions above in two groups were improved after corresponding treatments. ④In research group, 5 cases of patients relapsed after stopping using hemocoagulase and controlled after receiving 2-3 cycles of hemocoagulase again; 1 case of patient died of pulmonary infection and pulmonary alveolar hemorrhage, 1 case of patient died of leukemia relapse. In control group, 3 cases of patients relapsed and controlled after receiving bilateral interventional embolization of internal iliac artery under DSA; 1 case of patient died of severe pulmonary infection, 1 case of patient died of GVHD, and 1 case of patient died of intracranial hemorrhage. Conclusions Hemocoagulase is one of the effective and safe hemostatics, and it can be used to treat patients with HC post-allo-HSCT. It can effectively shorten the duration of HC. As the sample size in this study is small, the effect and safety of hemocoagulase in treatment of HC post-allo-HSCT, and whether it is worthy of clinical promotion, it still needs more large samples and randomized controlled trials to confirm. Key words: Hematopoietic stem cell transplantation; Hemorrhagic cystitis; Hemocoagulase

Objective This study was aimed to analysis the relationship of BK polyomavirus (BKV) and hemorrhagic cystitis (HC) in patients who received hematopoietic stem cell transplantation (HSCT). Methods Data of 80 patients who received HSCT and took regular urine test every week from June 2015 to April 2018 in the Third Xiangya Hospital of Central South University was retrospectively analyzed, they were 35 females and 45 males (aged 20-40 years, median age 30 years), and 31 cases with acute myeloid leukemia (AML), 24 cases with acute lymphoblastic leukemia (ALL), 15 cases with aplastic anemia (AA), 4 cases with chronic myeloid leukemia (CML), 6 cases with other diseases such as myelodysplastic syndrome (MDS) in the study population.The positive rate and incidence of HC were analyzed. Patients who infected with the BK virus were divided into HC group and non-HC group according to occurrence of HC.BK viral load were compared in two groups. Urine BK viral load were analyzed after logarithmic transformation. Data that conforms to a normal distribution is expressed as mean ± standard deviation. t test, ANOVA and ROC curve were used to statistical analysis. Skewed data is expressed in median (interquartile range), non-normal distribution parameters were compared by Wilcoxon test. Results Among 80 patients, 43 recipients (53.75%) became urinary BK positive, with 19 patients developed HC (23.75%), all of the 19 HC patients have urinary BK positive, and none of 37 BK-negative patients developed HC; the urine BKV level of the initial time and the peak time in HC group were (7.59±2.46) lg copy/ml, (10.56±1.71) lg copy/ml, the urine BKV level of the initial time and the peak time in non-HC group were (5.75±2.10) lg copy/ml, (7.31±2.29) lg copy /ml. The urine BKV level of the initial time and the peak time in HC group was higher than in non-HC group (t=2.642, P=0.012 and t=5.147, P=0.000 respectively), when analyzing the urine BKV level of the initial time in HC group and non-HC group, the best threshold is 5.23 lg copy/ml(1.68×105 copy/ml), with a sensitivity of 84.20% and specificity of 54.17%, when analyzing the urine BKV level of the peak time in HC group and non-HC group, the best threshold is 9.75 lg copy/ml(5.62×109 copy/ml), with a sensitivity of 84.20% and specificity of 83.33%, area under curve of each other were 0.728 (95% CI 0.575-0.881) and 0.875 (95% CI 0.769-0.981) respectively. Conclusions The BK viral load is closely related with HC in HSCT patients. The cut-off level of 1.68×105 copy/ml when analyzing the urine BKV level of the initial time, and the cut-off level of 5.62×109 when analyzing the urine BKV level of the peak time, help to forecast or auxiliary diagnose HC.(Chin J Lab Med, 2018, 41: 858-862) Key words: Cystitis; Hematopoietic stem cell transplantation; BK polyomavirus; Viral load; Urinalysis

Continuous Intravenous Injection of Mesna Is Powerful in Preventing Acute Hemorrhagic Cystitis in Hematopoietic Stem Cell Transplantation: 108 Cases report

Intractable haemorrhagic cystitis (HC) is a serious complication of chemotherapy (CT) and haematopoietic stem cell transplantation (HSCT). Hyperbaric oxygen treatment (HBOT) is a promising treatment option based on the similarities in injury pattern and observed histological changes with radiation induced HC, which is an approved indication. We present our experience with HBOT in HC occurring after CT and HSCT. Medical files of patients who underwent HBOT between the years 2000-2020 for HC that developed after chemotherapy and/or HSCT were reviewed. Demographic data, primary diagnosis, history of HC and details of HBOT were documented. Treatment outcomes were grouped as complete and partial healing, no response and deterioration. Twenty-five patients underwent a median of 12 HBOT sessions for HC occurring after CT and HSCT. Complete healing was observed in 11 patients whereas haematuria improved in seven patients. HC grades after HBOT were significantly better than referral grades. A significant correlation was shown with the number of HBOT sessions and change in haematuria. Patients who underwent seven or more HBOT sessions benefitted most. HBOT appears to be a safe and effective treatment for refractory HC following CT and HSCT. Higher quality evidence would be needed to prove efficacy. However, given the difficulty of conducting randomised controlled trials on such a vulnerable and small group of patients with few treatment options, and given the consistency of current observational evidence, HC occurring after CT and HSCT may be considered as an optional or investigational indication for HBOT.

Sulfolane (a metabolite of busulfan) Levels Could Predict Occurrence Of Hemorrhagic Cystitis In Children Receiving Busulfan Based Myeloablative Conditioning Before Hematopoietic Stem Cell Transplantation

Incidence of Adenovirus and BK Virus Reactivation and Diseases Following Reduced-Intensity Cord Blood Transplantation for Adult Patients.

BK Virus-Associated Hemorrhagic Cystitis Following Allogeneic Hematopoietic Stem Cell Transplantation; Incidence and Risk Factors

Hemorrhagic cystitis (HC) is a frequent and potentially severe complication following hematopoietic stem cell transplantation (HSCT) in children. It significantly affects the quality of life and prolongs hospitalization. Despite its frequency, no standardized management guidelines exist. This study aimed to describe the characteristics, risk factors, and treatments of HC in a pediatric HSCT population. We conducted a retrospective single-center study including all pediatric patients who underwent allogeneic HSCT between January 2007 and December 2022. HC was defined and graded according to the European Conference on Infections in Leukaemia (ECIL) guidelines. We analyzed risk factors, BK virus (BKV) viruria, treatments, and outcomes. HC occurred in 24 patients (14.7%), with a median onset at 27.5days post-HSCT. Acute graft-versus-host disease (aGVHD) was significantly associated with HC occurrence (45.8% vs. 19.4%, p = 0.01), particularly in its severe forms (p = 0.007). BKV was detected in 66.7% of HC cases. Viral load in urine was not significantly associated with HC severity or duration. All patients received supportive care; cidofovir was used in 79.2%, with increasing frequency in higher grade HC. Severe cases required multimodal management, including intravesical installations, hyperbaric oxygen therapy (HBO; 37.5%), and arterial embolization (all Grade 4 cases). No deaths were directly attributed to HC. HC remains a significant and morbid complication after pediatric HSCT. Our findings highlight the need for early identification of high-risk patients and access to timely, multidisciplinary interventions. Multicenter prospective studies are essential to standardize care and improve outcomes in this vulnerable population.