Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in X-linked Hyper IgM Syndrome: A Multicenter Chinese Cohort Study from CCBMT.

Background: Hemorrhagic cystitis (HC) is a frequent complication of cyclophosphamide (CP) therapy due to its toxic metabolite acrolein. Mesna is commonly used to prevent this toxicity.Aim: To assess the protective effects of resveratrol and cholecalciferol compared with mesna against CP-induced HC.Methods: This study involved 60 healthy male albino rats divided into six groups: Group I served as a normal control, Group II received untreated HC, Group III was administered resveratrol 20 minutes before CP injection, Group IV received cholecalciferol for 21 days alongside CP, Group V was treated with both resveratrol and cholecalciferol combined with CP, and Group VI was given CP with Mesna at 120 mg/kg.Results: CP markedly increased oxidative stress and inflammation, elevating Malondialdehyde (MDA), IL-1, urea, and creatinine, and causing hematuria and proteinuria. Resveratrol significantly improved these parameters; cholecalciferol had moderate protection, and their combination gave additive effects but was still less potent than mesna.Conclusion: Resveratrol pretreatment effectively reduced oxidative and inflammatory damage and improved renal function in CP-induced HC, showing promising protective potential.

Urologic oncologic emergencies represent a relatively narrow yet diverse group of critical conditions that require prompt recognition and intervention to prevent potentially life-threatening complications. These oncologic emergencies may arise as direct consequences of a malignancy, including local invasion, or as sequelae of surgical or therapeutic interventions. Common urologic emergencies include malignant obstructive uropathy or ureteral obstruction, which may lead to urosepsis or acute kidney injury; large volume hematuria and hemorrhagic cystitis, which both can result in substantial blood loss; renal hemorrhage, which can lead to hemodynamic instability; fistula formation; and postsurgical urinary leaks. Radiologists play a key role in promptly detecting and evaluating such emergencies and can help differentiate expected post-treatment findings from urgent or potentially life-threatening complications. Imaging not only helps to diagnose these emergencies but can also guide subsequent management strategies and thus is essential for optimizing patient outcomes. This review article aims to highlight the clinical and multi-modality imaging manifestations of urologic oncologic emergencies and their potential management strategies.

Cyclophosphamide (CYP) is an effective chemotherapeutic, but its use is limited by hemorrhagic cystitis caused by its toxic metabolite acrolein. Acrolein, when concentrated in the urine, triggers oxidative stress, leading to urothelial inflammation and cell death. Given that albumin is the most abundant plasma protein that contains free thiol groups capable of neutralizing electrophiles and oxidants, we, therefore, hypothesized that albumin could mitigate CYP-induced bladder injury. Here, we tested this hypothesis. In CYP-induced mouse cystitis, albumin administration markedly reduced bladder enlargement, edema, and hemorrhage, effectively normalizing the bladder weight. Albumin also reduced bladder oxidative injury and preserved the expression of anti-ferroptotic proteins, including the cystine/glutamate antiporter xCT and glutathione peroxidase 4 (GPX4). In addition, albumin-treated mice showed less leakage of inflammatory protein into bladder tissue. In vitro, albumin protected urothelial cells from acrolein-induced cell death. It also significantly prevented H2O2-induced cytotoxicity. Mechanistically, albumin acted as an extracellular scavenger that preferentially reacted with acrolein and H2O2, thereby sparing cellular components from oxidative damage. Notably, oral albumin supplementation similarly attenuated CYP-induced cystitis. Furthermore, albumin administration improved survival in a high-dose CYP toxicity model. These findings establish albumin as a potent protector against CYP-induced toxicity by sequestering acrolein and scavenging reactive oxygen species. Albumin supplementation could be a practical strategy to mitigate chemotherapy-associated bladder and systemic injury.

Hemorrhagic cystitis (HC) following hematopoietic stem cell transplantation (HSCT) is a significant event that can lengthen hospital stays and the need for care. The causes of HC can be multiple, but BK Polyomavirus (BKPyV) is the main protagonist in frequency. Currently, the clinical tool widely used to detect the presence of the virus in urine is PCR-based viral genome testing. We have developed a new rapid test for the antigenic detection of BKPyV in urine. The aim of this diagnostic study was to retrospectively evaluate the performance of this new assay as compared to BKPyV PCR on urine from HSCT patients with suspected HC. 49 samples from 49 different patients were evaluated, 20 of whom presented with HC. Of these 20 samples, 19 (95 %) were positive by the rapid antigen test. Of the 37 BKPyV PCR-positive samples, 31 were above 7 log10 copies/mL, including the 20 patients with HC. Thus, the overall performance of the rapid test for HC is greatly improved compared with PCR, with specificity rising from 62.1 % to 86.2 % and positive predictive value from 64.5 % to 82.6 %. In conclusion, this new tool could be implemented as a point-of-care test to rapidly confirm or rule out a suspicion of BKPyV-HC after HSCT.

Radiation-induced haemorrhagic cystitis (HC) is a late complication of radiotherapy. Haematuria may be refractory to medical or endoscopic treatment. Case 1 is a patient who underwent pelvic radiotherapy for bladder cancer. The patient developed radiation-induced HC 5 years after radiotherapy. Case 2 is a patient who underwent total prostatectomy followed by salvage radiotherapy and developed radiation-induced HC 15 years later. In both cases, transarterial embolisation of the vesical arteries was performed after refractoriness to medical treatment without recurrence. Transarterial embolisation of the vesical arteries is a potential treatment option for refractory radiation-induced HC.

Pathophysiology and multi-target prevention strategies for cyclophosphamide-induced bladder injury.

The purpose of our study was to assess if spinacetin (SPC), a flavonoid found in spinach, can alleviate the cyclophosphamide (CYP)-induced changes in cystometric and inflammatory parameters indicative of the development of hemorrhagic cystitis. The animal experiments were conducted in female Wistar rats. The cohort of 60 animals was grouped as follows: I-control, II-CYP group, III-SPC group, and IV-CYP + SPC group. The cystometry and biochemical analyses were performed after a fortnight of SPC administration. SPC was found to restore normal cystometric parameters in CYP-induced cystitis and, similarly, it normalized c-Fos expression changes in the central micturition regions. SPC further prevented a massive increase in the bladder wall thickness/permeability due to exposition to CYP administration. CYP instillation resulted in the elevation of biomarkers found in urine (brain-derived neurotrophic factor, BDNF, and nerve growth factor, NGF), and in the bladder detrusor muscle (Rho kinase and vesicular acetylcholine transporter, VAChT), which were successfully restored after administration of SPC. As for the biomarkers in the bladder urothelium, the CYP-induced increases in TNF-α, IL-1β, IL-6, calcitonin gene-related peptide (CGRP), malondialdehyde, 3-nitrotyrosine, insulin-like growth factor-binding protein 3 (IGFBP-3), occludin, organic cation transporter 3 (OCT-3), orosomucoid-1 (ORM1), pituitary adenylate cyclase receptor 1 (PAC1), synaptosomal-associated protein 23 (SNAP23), SNAP25, and synaptic vesicle glycoprotein (SV2A) levels were attenuated by SPC. Finally, CYP administration resulted in a decrease in the heparin-binding EGF-like growth factor (HB-EGF), hemopexin (HPX), T-H protein, and tight junction protein (Z01), and we noted the successful restoration of all these changes in concentrations after application of SPC. In summary, SPC robustly mitigated cyclophosphamide (CYP)-induced cystometric dysfunction and biochemical alterations characteristic of iatrogenic hemorrhagic cystitis. These findings position SPC as a compelling therapeutic candidate and warrant further translational investigation for the management of CYP-induced bladder injury.

This retrospective study aimed to compare reduced-dose anti-thymocyte globulin (ATG) plus post-transplant cyclophosphamide (PTCy) versus standard ATG for GVHD prophylaxis in haplo-HSCT. A total of 61 patients (median age, 35 years; range, 4–62) who received a myeloablative conditioning regimen between 2019 and 2024 were included. Patients received either reduced-dose ATG with PTCy (n = 30) or standard ATG (n = 31). The primary outcome was chronic GVHD (cGVHD) incidence. With a 38.5-month median follow-up, the 2-year cGVHD rate was significantly lower in the ATG-PTCy group (10.0% vs. 38.7%, p = 0.012). Rates of grade II-IV acute GVHD, engraftment times, infections (CMV/EBV), non-relapse mortality, and relapse were statistically comparable between groups. Consequently, 2-year overall survival (83.3% vs. 77.4%) and disease-free survival (80.0% vs. 71.0%) showed no significant difference. A favorable trend toward less hemorrhagic cystitis was observed with ATG-PTCy. In conclusion, the combination of reduced-dose ATG with PTCy is associated with a significantly reduced risk of chronic GVHD after haplo-HSCT.

Radiotherapy of the pelvis and abdomen can have significant negative long-term effects on the bladder and urethra. Applying the PICO criteria, we reviewed the MEDLINE/PUBMED databases over a 10-year period for literature on the incidence and prevalence of late adverse effects of radiotherapy on the lower urinary tract; the work-up and management of these adverse effects. Overactive bladder, hemorrhagic cystitis, fistula, stress urinary incontinence, bladder neck contracture, urethral stricture, and secondary malignancy were investigated as late complications of radiotherapy on the bladder and urethra. These sequalae may present in the decades following radiotherapy usually with greater symptom severity than those non-irradiated and will often have less favourable outcomes with traditional management strategies that are applied in the absence of radiation. Experimental therapies are being trialed. Our findings reinforce that patients with radiotherapy-related complications most often have poorer outcomes with traditional management strategies such as male urethral slings for stress incontinence and fistula repair, however this review identified successful outcomes for treatments such as the artificial urethral sphincter for incontinence, and hyperbaric oxygen therapy for hemorrhagic cystitis. Further research is required - particularly with a focus on the irradiated female population.

Combination therapy with ifosfamide and doxorubicin (AI) is a standard treatment for malignant soft tissue tumors. However, we have encountered a high incidence of edema in patients with AI receiving the standard supportive care regimen at our hospital. Based on a report indicating that dexamethasone has a noninferior antiemetic effect in chemotherapy regimens even with a shorter duration of administration, the total infusion volume was reduced from 3,000 to 2,000 mL, and the administration period of dexamethasone and granisetron was shortened from 4 to 3 days after discussion with physicians. We conducted a retrospective descriptive analysis of patients who received the first course of AI for malignant soft tissue tumors in our institution between May 1, 2014, and March 31, 2020 to examine the impact of changing the regimen. There were 17 patients in the 3,000-mL group and 18 patients in the 2,000-mL group. The incidence of edema decreased from 82％ in the 3,000-mL group to 44％ in the 2,000-mL group. No decrease in creatinine clearance was observed after the treatment in either group, and no cases of hemorrhagic cystitis developed. The complete response rates were 65％ and 50％ (acute period) and 76％ and 44％ (delayed period) for the 3,000 mL and 2,000 mL groups, respectively. Thus, AI chemotherapy could be administered with reduced edema, without affecting renal function, by reducing the amount of fluid administered and the number of days of antiemetic drug administration. However, delayed vomiting remains an issue that needs to be addressed.

Opsoclonus is a rare oculomotor disorder characterized by chaotic, multidirectional saccades, typically associated with paraneoplastic or parainfectious autoimmune mechanisms [1]. While neurological complications may occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT), isolated opsoclonus triggered by viral reactivation is exceptional [2]. We report a case of opsoclonus associated with adenovirus-associated hemorrhagic cystitis (AdV-HC) after allo-HSCT. A 54-year-old man with acute myeloid leukemia in his second complete remission (CR) underwent allo-HSCT from an HLA-C allele-mismatched unrelated donor. The conditioning regimen included fludarabine, busulfan, and 4 Gy total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of rabbit anti-thymocyte globulin, tacrolimus, and short-term methotrexate. Neutrophil engraftment was achieved on Day 12. Grade III acute GVHD involving the skin and gut occurred on day 16 but resolved with prednisolone, ruxolitinib, and mesenchymal stem cells. On Day 113, he developed macroscopic hematuria and impaired renal function. AdV-HC was diagnosed based on positive polymerase chain reaction (PCR) results in blood and urine. Although his urinary symptoms improved with hydration and reduction of immunosuppression, he developed severe dizziness approximately 3 weeks after the onset of AdV-HC. Neurological examination revealed chaotic, multidirectional, jerky eye oscillations consistent with opsoclonus, exacerbated by attempted pursuit (Figure 1, Supporting Information). Myoclonus and ataxia were absent. Brain magnetic resonance imaging was unremarkable, ruling out the possibility of posterior reversible encephalopathy syndrome or ischemic events. Cerebrospinal fluid (CSF) analysis revealed normal cell count, protein, and glucose levels; however, the presence of oligoclonal bands and an elevated IgG index indicated IgG synthesis within the central nervous system. CSF PCR for viruses, including herpes simplex virus, human herpesvirus 6, and AdV, was negative. A comprehensive workup for alternative etiologies, including paraneoplastic antibody panel (including anti-Hu and anti-Ri) and whole-body computed tomography, was unremarkable. Bone marrow examination confirmed sustained CR of AML. At the onset of opsoclonus, acute GVHD was in CR and was quiescent under tapering immunosuppression with prednisolone 7.5 mg, tacrolimus 0.4 mg, and ruxolitinib 20 mg daily, without any concurrent exacerbations or newly emerging systemic manifestations. Based on these findings, a diagnosis of parainfectious opsoclonus secondary to AdV infection was made. The patient received cidofovir for AdV-HC, resulting in complete viral clearance. For the opsoclonus, he was treated with clonazepam, two courses of methylprednisolone pulse therapy, and intravenous immunoglobulin. His symptoms resolved almost completely approximately nine weeks after the onset of opsoclonus. Opsoclonus is usually accompanied by ataxia and myoclonus as part of the opsoclonus–myoclonus syndrome (OMS), and is most often paraneoplastic in adults [1]. In this case, a paraneoplastic etiology was considered unlikely based on the negative results of comprehensive systemic evaluation and paraneoplastic antibody screening. Parainfectious OMS has been reported with various pathogens and is thought to arise from immune-mediated mechanisms, in which molecular mimicry triggers an autoimmune attack on neuronal structures, leading to disinhibition of the oculomotor region of the cerebellar fastigial nucleus [3]. The delayed onset after AdV-HC, evidence of intrathecal IgG synthesis, and favorable response to immunotherapy support an autoimmune mechanism rather than direct viral invasion. To our knowledge, this is the first reported case of adult-onset opsoclonus associated with adenovirus infection after allo-HSCT. Early recognition of characteristic eye movements during recovery from acute viral infections, including AdV, is crucial, as timely immunotherapy can lead to substantial neurological recovery. We would like to thank Shota Yoshida, Takahide Ara, Toshihiro Matsukawa, and Masao Nakagawa (Department of Hematology), as well as Kazuki Yamada, Taichi Nomura, Hiroaki Yaguchi, and Ichiro Yabe (Department of Neurology) for patient care. The authors have nothing to report. Patient's consent was obtained for publication of the case. The authors declare no conflicts of interest. This article contains all the data that was obtained during the research. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Cyclophosphamide (CYP) may through its toxic metabolite, acrolein, induce hemorrhagic cystitis and bladder hyperactivity. Previous studies demonstrated intra-iliac arterial administration of adipose derived mesenchymal stem cells (ADSC)-derived microvesicles with less immune response and adverse effects than ADSC itself may confer anti-oxidative stress and anti-inflammatory potential to improve bladder dysfunction. We explored whether ADSC-derived microvesicles may prevent CYP-induced bladder cystitis and overactivity. Female Wistar rats were divided into control (Con), CYP (Cy), CYP+microvesicles (CyM), and microvesicles treated control (CoM) groups. Con rats were intraperitoneally treated with saline, while the Cy rats were induced by intraperitoneally administered CYP (100 mg/kg body weight). We injected ADSC-derived microvesicles at the dosage of 15 μg/ml via intra-iliac artery to the rats with or without CYP treatment. We measured the responses of transcystometrogram, pathology, expression of muscarinic receptors (M3) and purinergic receptors (P2X7), pyroptosis related Caspase 1 and IL-1β, xCT/Gpx4 related ferroptosis by western blot in CYP-treated bladders. Wire myography of the urinary bladder was determined. ADSC-derived microvesicles effectively decreased micturition frequency (overactivity), inflammation and fibrosis in CyM rats versus Cy rats. ADSC-derived microvesicles efficiently downregulated P2X7 and M3 receptor expression, Caspase 1/IL-1β mediated pyroptosis, xCT/Gpx4 regulated ferroptosis and restored Bcl-2/HO-1 mediated antioxidant defense mechanisms in CYP-induced cystitis. The pathologic results also displayed the effective reduction of bladder immune cell infiltration (inflammation) and fibrosis, and the preservation of the integrity in the urothelium by the treatment of ADSC-derived microvesicles. ADSC-derived microvesicles can ameliorate CYP-induced bladder overactivity, inflammation, fibrosis, ferroptosis and pyroptosis.

ObjectiveTo analyze the clinical characteristics and risk factors of acute kidney injury (AKI) after hematopoietic stem cell transplantation (HCT) in children.MethodsThe clinical data of children who underwent HCT at our hospital from August 2016 to December 2023 were retrospectively analyzed, including age, sex, primary disease, mode of transplantation, conditioning regimen, serum creatinine (SCr) before transplantation, and the highest value of SCr from the beginning of conditioning to 100 days after transplantation. AKI was diagnosed and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, primarily based on changes in SCr. We performed univariate and multivariate logistic regression analyses to determine the risk factors for AKI, including the time of AKI onset, transplantation-related complications (sepsis, acute graft-versus-host disease (aGVHD), thrombotic microangiopathy (TMA), hepatic sinusoidal gap obstruction syndrome, hemorrhagic cystitis, cytomegalovirus infection, and Epstein-Barr virus infection). Cumulative incidence competing risk analysis was used to assess AKI incidence, with death as a competing event. Risk factors were analyzed using multivariable Cox proportional hazards regression with time-dependent covariates for post-transplantation complications.ResultsA total of 299 patients were included. The cumulative incidence of AKI was 73.6% (220/299), with 131, 62, and 27 cases at Stage I, II, and III, respectively. The median time to AKI onset was 24 days (range: −4 to +91 days). Multivariable analysis showed that human leukocyte antigen (HLA) mismatch, hepatic sinusoidal obstruction syndrome (SOS), aGVHD, TMA, and cytomegalovirus/Epstein-Barr virus (CMV/EBV) infection were independent risk factors for AKI (P < 0.05). AKI was significantly associated with worse overall survival (Log-rank test, P < 0.001).ConclusionsAKI is a common complication of HCT in children. HLA mismatch and post-transplantation complications are independent risk factors. Severe AKI is closely associated with poor prognosis. Early monitoring and management of AKI are crucial for improving outcomes.

ObjectivesCladribine, a synthetic analog of deoxyadenosine, exhibits potent activity against hematological malignancies. While cladribine-containing regimens combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been proposed as a potential strategy to improve outcomes in relapsed or refractory (R/R) acute myeloid leukemia (AML), additional clinical evidence is needed, particularly in pediatric populations. This single-center retrospective study aimed to describe the efficacy and safety of a cladribine-based conditioning regimen for allo-HSCT in children with R/R AML.Materials and methodsClinical data of 16 children with R/R AML who underwent allo-HSCT following a cladribine-based conditioning regimen at our hospital from October 2020 to June 2024 were analyzed retrospectively. Key outcomes included hematopoietic reconstruction, regimen-related toxicity (RRT), cumulative incidence of graft-versus-host disease (GVHD), infection profiles, overall survival (OS), disease-free survival (DFS), relapse rate, and non-relapse mortality (NRM). Flow-cytometry minimal residual disease (MRD) results before HSCT were collected and analyzed as an additional key baseline index.ResultsAll 16 patients attained hematopoietic reconstruction, with pre-transplant flow-cytometry MRD negative in 13 cases (81.25%) and positive (MRD ≥0.01%) in three cases (18.75%). The median time of neutrophil and platelet engraftment was 12 (10–16) days and 15 (10–25) days, respectively. The incidence of I/II grade RRT was 31.3% (oral cavity: three cases, liver: two cases), with no III/IV grade RRT observed. The cumulative incidence of acute GVHD (aGVHD) was 50.0% (grade I/II skin: five cases, grade IIIl: three cases). Among 15 evaluable patients, the cumulative incidence of chronic GVHD (cGVHD) was 26.7% (local skin: three cases, ocular keratoconjunctivitis sicca: one case). Post-transplant infections occurred in 31.3% of patients, predominantly viral pathogens: one case of BK virus-associated hemorrhagic cystitis, one case of BK virus combined with bacterial infection, and three cases of cytomegalovirus (CMV) DNAemia. The median follow-up time was 28.03 (11.67–55.34) months (follow-up cutoff: 30 June 2024). Using the Kaplan–Meier method, the 1-year OS rate was 87.5% (95% CI: 65.2%−96.4%), and the 1-year DFS rate was 87.4% (95% CI: 64.9%−96.3%). The relapse rate and NRM were both 6.3% (95% CI: 0.8%−29.1%); the NRM case was confirmed as bronchiolitis obliterans syndrome (BOS) induced by pulmonary cGVHD.ConclusionIn this small single-center retrospective series, the cladribine-based conditioning regimen was associated with favorable hematopoietic reconstruction, mild RRT, and promising survival outcomes in children with R/R AML, even in partial patients with pre-transplant MRD positivity. However, due to the limited sample size, single-arm design, and lack of a control group, conclusions regarding superiority (e.g., improved OS or reduced relapse) cannot be drawn. Larger prospective multi-center studies are required to validate these preliminary findings.

Pilot study of early BK polyomavirus in the urine and risk of hemorrhagic cystitis after allogeneic hematopoietic cell transplantation.

Repositioning offers a cost-effective approach to discovering new therapeutic applications for existing medications. Ambroxol, primarily used as a mucolytic for respiratory diseases, has demonstrated anti-inflammatory, analgesic, and antioxidant properties, suggesting potential benefits in non-pulmonary conditions. This study conducted a systematic review to evaluate the efficacy of ambroxol in experimental disease models unrelated to the respiratory system. Following registration in the Open Science Framework and adherence to the PICO strategy for formulating the guiding question, searches were performed in PUBMED/MEDLINE, EMBASE, and SCOPUS using the keywords: (Ambroxol) AND (Anti-Inflammatory Agents OR Analgesics OR Antioxidants) AND (Animals OR invivo). The SYRCLE tool assessed methodological quality. Among 353 identified records, eight articles met eligibility criteria. These studies investigated ambroxol's effects in models of gastric lesions, neuropathic pain, psoriasis-like skin inflammation, hemorrhagic cystitis, and ischemia/reperfusion injuries in the liver and kidneys. Ambroxol doses ranged from 5 to 1000 mg/kg, predominantly administered orally. Its antioxidant properties were demonstrated by reducing free radicals and increasing enzymatic activity (SOD, CAT, GSH). Anti-inflammatory effects included a decrease in pro-inflammatory cytokines (TNF-α, IL-1β) and histological improvements. Antinociceptive action was observed through inhibition of voltage-gated sodium channels and reduction of oxidative stress, alleviating neuropathic pain. Despite ambroxol's widespread clinical use, limited research has explored its non-respiratory applications. Existing studies suggest its promising therapeutic potential, reinforcing the need for further investigation into its role as an alternative treatment for various inflammatory and oxidative stress-related conditions beyond pulmonary diseases.

Prognostic Impact of BK Polyomavirus Viremia Detected by Multiplex Plasma PCR Following Allogeneic Hematopoietic Cell Transplantation.

Low-Dose Post-Transplant Cyclophosphamide in Haploidentical Stem Cell Transplantation: A Systematic Review.

A0724 Hyperbaric oxygen therapy in patients with radiation-induced hemorrhagic cystitis