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Moaveni AK, Seyed Taher SF, Ghavamzadeh A, Hamidieh AA, Kajbafzadeh AM. The potential of uroflowmetry to predict and detect hemorrhagic cystitis following hematopoietic stem cell transplantation. J Pediatr Urol 2025; 21:426-433. [PMID: 39603892 DOI: 10.1016/j.jpurol.2024.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 09/28/2024] [Accepted: 11/05/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND Hemorrhagic cystitis (HC) is a serious complication following hematopoietic stem cell transplantation (HSCT) associated with significant morbidity and mortality. Early identification of at-risk patients and prompt diagnosis are crucial for effective management. This prospective cohort study evaluated the potential of uroflowmetry as a predictive tool for detecting HC in pediatric HSCT patients. METHODS Thirty-one children who underwent allogeneic HSCT were enrolled. Uroflowmetry was performed on admission (Day 0), post-HSCT Day 1 and Day 15, and at HC onset. Uroflowmetric parameters, including maximum flow rate (Qmax), average flow rate (Qavg), voided volume (VV), and flow curve shape, were compared between HC and non-HC patients. RESULTS The incidence of HC within 100 days post-HSCT was 58 %, with a mean onset time of 35 days. At baseline (Day 0), HC patients had significantly lower Qmax (12.5 vs. 17.8 mL/s), Qavg (6.8 vs. 9.5 mL/s), and VV (185 vs. 245 mL) compared to non-HC patients (all p < 0.05). Age-stratified analysis revealed the observation of these differences across all age groups. At HC onset, compared to Day 0, patients experienced a significant decrease in Qmax (8.7 vs. 12.5 mL/s) and Qavg (4.2 vs. 6.8 mL/s) (both p < 0.05). Flow curve analysis demonstrated a shift from bell-shaped to interrupted curves in HC patients over time. CONCLUSIONS Uroflowmetry can potentially predict and detect HC in pediatric HSCT patients. Lower baseline uroflowmetric parameters may identify patients at higher risk for HC, while a significant decrease in these parameters from baseline may indicate HC onset. Uroflowmetry is a simple, non-invasive tool that can be performed at home and monitored remotely, facilitating early detection and intervention for HC in this population.
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Affiliation(s)
- Amir Kian Moaveni
- Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Farshad Seyed Taher
- Hematology, Oncology, and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ardeshir Ghavamzadeh
- Hematology, Oncology, and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Ali Hamidieh
- Pediatric Cell and Gene Therapy Research Centre, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdol-Mohammad Kajbafzadeh
- Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
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Kaçar D, Güzelküçük Z, Koca Yozgat A, Işık M, Özlü SG, Yaralı N. BK Virus-Related Haemorrhagic Cystitis in Non-Transplanted Children With Leukaemia. J Paediatr Child Health 2025. [PMID: 40119781 DOI: 10.1111/jpc.70042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 03/12/2025] [Accepted: 03/14/2025] [Indexed: 03/24/2025]
Abstract
BACKGROUND Although it is well-known in transplant recipients, BK virus (BKV)-related haemorrhagic cystitis (HC) is an unexpected complication in children with leukaemia on standard chemotherapy. METHODS This retrospective observational study reported non-transplanted children who experienced BKV-related HC during acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia treatment. Disease status, HC grade, BKV copy number in urine, blood counts, imaging findings, HC treatments and preceding oral mucositis and posterior reversible encephalopathy syndrome (PRES) were evaluated. RESULTS Twenty-three children with leukaemia were tested in urine BKV polymerase chain reaction for haematuria aetiology, and BKV was detected in 14 (60.9%). Seven of the patients (50%) had T cell ALL, 10 were 10 years old and older (71.4%) and 11 were male (78.6%). All patients were in the consolidation phase of therapy, and except one, all were in remission during HC. The mean BKV copy number in the urine was 0.443 × 109 ± 0.203 × 109/mL. Four patients (28.6%) had grade I, seven (50.0%) had grade II, and three patients (21.4%) had grade III HC. HC grades were correlated with neutrophil to lymphocyte ratio (rs = 0.616, p = 0.019). Preceding/concomitant oral mucositis in nine (64.3%) and PRES in the previous 3 months in five patients (35.7%) have been noted. CONCLUSIONS BKV-related HC is a potential complication of patients with leukaemia during the consolidation phase of treatment. The risk factors of BKV-related HC in children with leukaemia are similar to those of haematopoietic stem cell transplantation recipients.
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Affiliation(s)
- Dilek Kaçar
- Ankara Bilkent City Hospital, Department of Paediatric Haematology Oncology, University of Health Sciences, Ankara, Türkiye
| | - Zeliha Güzelküçük
- Ankara Bilkent City Hospital, Department of Paediatric Haematology Oncology, Ankara, Türkiye
| | - Ayça Koca Yozgat
- Ankara Bilkent City Hospital, Department of Paediatric Haematology Oncology, University of Health Sciences, Ankara, Türkiye
| | - Melek Işık
- Ankara Bilkent City Hospital, Department of Paediatric Haematology Oncology, Ankara, Türkiye
| | - Sare Gülfem Özlü
- Ankara Bilkent City Hospital, Department of Paediatric Nephrology, Ankara Yıldırım Beyazıt University, Ankara, Türkiye
| | - Neşe Yaralı
- Ankara Bilkent City Hospital¸ Department of Paediatric Haematology Oncology, Ankara Yıldırım Beyazıt University, Ankara, Türkiye
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Mendoza MA, Imlay H. Polyomaviruses After Allogeneic Hematopoietic Stem Cell Transplantation. Viruses 2025; 17:403. [PMID: 40143330 PMCID: PMC11946477 DOI: 10.3390/v17030403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/28/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Polyomaviruses (PyVs) are non-enveloped double-stranded DNA viruses that can cause significant morbidity in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, particularly BK polyomavirus (BKPyV) and JC polyomavirus (JCPyV). BKPyV is primarily associated with hemorrhagic cystitis (HC), while JCPyV causes progressive multifocal leukoencephalopathy (PML). The pathogenesis of these diseases involves viral reactivation under immunosuppressive conditions, leading to replication in tissues such as the kidney, bladder, and central nervous system. BKPyV-HC presents as hematuria and urinary symptoms, graded by severity. PML, though rare after allo-HSCT, manifests as neurological deficits due to JCPyV replication in glial cells. Diagnosis relies on nucleic acid amplification testing for DNAuria or DNAemia as well as clinical criteria. Management primarily involves supportive care, as no antiviral treatments have proven consistently effective for either virus and need further research. This review highlights the virology, clinical presentations, and management challenges of PyV-associated diseases post-allo-HSCT, emphasizing the need for improved diagnostic tools and therapeutic approaches to mitigate morbidity and mortality in this vulnerable population.
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Affiliation(s)
| | - Hannah Imlay
- Division of Infectious Diseases, Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA;
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Dell'Orso G, Carlucci M, Cesaro S, Olcese E, Balduzzi A, Vendemini F, Catti M, Saglio F, Compagno F, Maximova N, Rabusin M, Menconi MC, Perruccio K, Soncini E, Tambaro FP, Tintori V, Pagliara D, Faraci M. An expert consensus on prevention, diagnosis, and management of hemorrhagic cystitis in pediatric hematopoietic cell transplantation, on behalf of the Infectious Disease and Hematopoietic Cell Transplant Working groups of Italian Pediatric Hematology Oncology Association (AIEOP). Bone Marrow Transplant 2024; 59:1302-1308. [PMID: 38909124 DOI: 10.1038/s41409-024-02320-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 05/15/2024] [Accepted: 05/23/2024] [Indexed: 06/24/2024]
Abstract
The optimal management of hemorrhagic cystitis (HC) in hematopoietic stem cell transplantation (HCT) is debated, both for early onset HC (EOHC) secondary to chemotherapy toxicity and BK Polyomavirus (BKPyV)-related HC, due to the lack of controlled trials, particularly referred to pediatric setting. Actually, clinical practice is mainly based on guidelines of the European Conference on Infections in Leukemia, 6th edition, which considers both adult and pediatric populations but concludes that, despite much progress in understanding the pathogenesis, epidemiology, and risk factors, this complication still represents a disabling unmet clinical need with limited prophylactic and therapeutic options. Additionally, the Guidelines of the American Society of Clinical Oncology define the management of chemotherapeutic toxicity independently from the patients' population. A panel of experts belonging to the Hematopoietic Cell Transplant and Infectious Disease Working Group (WG) of Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) developed a consensus to define the best practices in prevention, diagnosis, and management of HC in pediatric HCT setting.
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Affiliation(s)
- Gianluca Dell'Orso
- Hematopoietic Stem Cell Transplantation Unit, Department of Pediatric Hematology-Oncology, IRCCS, Istituto Giannina Gaslini, Genova, Italy.
| | - Marcello Carlucci
- Pediatric Surgery Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy
| | - Simone Cesaro
- Pediatric Hematology Oncology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Evelina Olcese
- Hematopoietic Stem Cell Transplantation Unit, Department of Pediatric Hematology-Oncology, IRCCS, Istituto Giannina Gaslini, Genova, Italy
| | - Adriana Balduzzi
- Pediatric Transplantation Unit, Department of Medicine and Surgery, University of Milan-Bicocca-Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
- Clinica Pediatrica, Università degli Studi di Milano Bicocca, Fondazione MBBM/Ospedale San Gerardo, ASST, Monza, Italy
| | - Francesca Vendemini
- Pediatric Transplantation Unit, Department of Medicine and Surgery, University of Milan-Bicocca-Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Massimo Catti
- Division of Pediatric Urology, Department of Pediatrics and Pediatric Specialties, Regina Margherita Children's Hospital, Torino, Italy
| | - Francesco Saglio
- Pediatric Oncohematology, Stem Cell Transplantation and Cell Therapy Division, A.O.U. Città della Salute e della Scienza-Regina Margherita Children's Hospital, Torino, Italy
| | - Francesca Compagno
- Pediatric Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Natalia Maximova
- Pediatric Hematology-Oncology Unit, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo, ", Trieste, Italy
| | - Marco Rabusin
- Pediatric Hematology-Oncology Unit, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo, ", Trieste, Italy
| | | | - Katia Perruccio
- Pediatric Oncology Hematology, Mother and Child Health Department, Santa Maria della Misericordia Hospital, Perugia, Italy
| | - Elena Soncini
- Pediatric Oncology-Haematology and Bone Marrow Transplantation (BMT) Unit, Spedali Civili di Brescia, Brescia, Italy
| | | | - Veronica Tintori
- Department of Pediatric Hematology/Oncology and Hematopoietic Stem Cell Transplantation, Meyer Children's University Hospital, Firenze, Italy
| | - Daria Pagliara
- Department of Hematology/Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Roma, Italy
| | - Maura Faraci
- Hematopoietic Stem Cell Transplantation Unit, Department of Pediatric Hematology-Oncology, IRCCS, Istituto Giannina Gaslini, Genova, Italy
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Liu P, Bai K, Zhang Z, Sun J. Analysis of early clinical signs and risk factors for severe hemorrhagic cystitis after stem cell transplantation in children. Int J Urol 2024; 31:335-341. [PMID: 38180136 DOI: 10.1111/iju.15365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 11/27/2023] [Indexed: 01/06/2024]
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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Affiliation(s)
- Pengtao Liu
- Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kaiping Bai
- Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhiyuan Zhang
- Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Sun
- Department of Urology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Yao X, Xu Z, Duan C, Zhang Y, Wu X, Wu H, Liu K, Mao X, Li B, Gao Y, Xu H, Wang X. Role of human papillomavirus and associated viruses in bladder cancer: An updated review. J Med Virol 2023; 95:e29088. [PMID: 37706751 DOI: 10.1002/jmv.29088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/29/2023] [Accepted: 08/31/2023] [Indexed: 09/15/2023]
Abstract
Bladder cancer (BC) is a complex disease affecting the urinary system and is regulated by several carcinogenic factors. Viral infection is one such factor that has attracted extensive attention in BC. Human papillomavirus (HPV) is the most common sexually transmitted infection, and although multiple researchers have explored the role of HPV in BC, a consensus has not yet been reached. In addition, HPV-associated viruses (e.g., human immunodeficiency virus, herpes simplex virus, BK virus, and JC virus) appear to be responsible for the occurrence and progression of BC. This study systematically reviews the relationship between HPV-associated viruses and BC to elucidate the role of these viruses in the onset and progression of BC. In addition, the study aims to provide a greater insight into the biology of HPV-associated viruses, and assess potential strategies for treating virus-induced BC. The study additionally focuses on the rapid development of oncolytic viruses that provide a potentially novel option for the treatment of BC.
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Affiliation(s)
- Xiangyang Yao
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zhenzhen Xu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Chen Duan
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yangjun Zhang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xiaoliang Wu
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huahui Wu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Kai Liu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xiongmin Mao
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Bo Li
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yang Gao
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Hua Xu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Wuhan, China
- Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China
- Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China
| | - Xinghuan Wang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Wuhan, China
- Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China
- Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China
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Ersoy GZ, Bozkurt C, Aksoy BA, Öner ÖB, Aydoğdu S, Çipe F, Sütçü M, Özkaya O, Fışgın T. Evaluation of the risk factors for BK virus-associated hemorrhagic cystitis in pediatric bone marrow transplantation patients: Does post-transplantation cyclophosphamide increase the frequency? Pediatr Transplant 2023; 27:e14364. [PMID: 35851981 DOI: 10.1111/petr.14364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/31/2022] [Accepted: 07/04/2022] [Indexed: 01/24/2023]
Abstract
BACKGROUND BKV-HC is one of the most significant complications of HSCT. This retrospective study aimed to determine the frequency of BKV-HC in pediatric patients undergoing HSCT, detect the associated risk factors for the development of BKV-HC, and explore the effects of post-transplantation Cy use. METHODS Three hundred twenty-seven patients (girls: 121, boys: 206) were analyzed according to sex, conditioning regimen, transplantation type, donor relatedness, stem cell source, the presence and grade of aGVHD, CMV co-existence, and Cy use. RESULTS Multivariate analysis confirmed the prognostic importance of age (OR: 4.865), TBI use, the presence of aGVHD (OR: 2.794), CMV coinfection (OR: 2.261), and Cy use (OR: 27.353). A statistically significant difference was found between the mean BKV-HC follow-up times compared with post-transplantation Cy intake (p < .001). The BKV-HC rate increased as the number of risk factors of the patient increased. CONCLUSION BKV-HC is an essential complication of HSCT primarily associated with Cy use, the presence of aGVHD, and donor relatedness. The present study shows that the use of Cy in the post-transplantation period further increases BKV-HC risk in pediatric patients, regardless of dose.
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Affiliation(s)
- Gizem Zengin Ersoy
- Altınbaş University Medical Park Bahçelievler Hospital Pediatric Hematology Oncology & Pediatric Bone Marrow Transplantation Unit, İstanbul, Turkey
| | - Ceyhun Bozkurt
- Medical Park Bahçelievler Hospital Pediatric Hematology Oncology & Pediatric Bone Marrow Transplantation Unit, İstinye University Pediatric Hematology Oncology, Istanbul, Turkey
| | - Basak Adakli Aksoy
- Altınbaş University Medical Park Bahçelievler Hospital Pediatric Hematology Oncology & Pediatric Bone Marrow Transplantation Unit, İstanbul, Turkey
| | - Özlem Başoğlu Öner
- Altınbaş University Medical Park Bahçelievler Hospital Pediatric Hematology Oncology & Pediatric Bone Marrow Transplantation Unit, İstanbul, Turkey
| | - Selime Aydoğdu
- Umraniye Research & Training Hospital Pediatric Hematolgy & Oncology Department, Medical Sciences University, Istanbul, Turkey
| | - Funda Çipe
- Altınbaş University Medical Park Bahçelievler Hospital Pediatric Allergy-Immunology & Pediatric Bone Marrow Transplantation Unit, İstanbul, Turkey
| | - Murat Sütçü
- İstinye University Pediatric Infectious Diseases, Istanbul, Turkey
| | - Ozan Özkaya
- İstinye University Pediatric Nephrology, Istanbul, Turkey
| | - Tunç Fışgın
- Altınbaş University Medical Park Bahçelievler Hospital Pediatric Hematology Oncology & Pediatric Bone Marrow Transplantation Unit, İstanbul, Turkey
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Rostami T, Aghabeigi S, Kiumarsi A, Kasaeian A, Parizi MK, Mirhosseini A, Rostami MR, Babakhani D, Tavakoli F, Janbabai G, Mousavi SA. Incidence of hemorrhagic cystitis following unmanipulated peripheral blood stem cell transplantation in acute Leukemia: A retrospective single-center risk factor analysis. J Pediatr Urol 2023; 19:54.e1-54.e8. [PMID: 36443142 DOI: 10.1016/j.jpurol.2022.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 10/19/2022] [Accepted: 11/06/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND Hemorrhagic cystitis (HC) is an important adverse event experienced after hematopoietic stem cell transplantation (HSCT). Severe HC could lead to significant morbidity, prolonged hospitalization with increased health-care costs, and may cause considerable mortality. OBJECTIVES In order to investigate the influence of different contributing factors other than BK viruria on HC occurrence in a homogenous population, we retrospectively analyzed the potential risk factors. STUDY DESIGN We conducted a retrospective study among 200 patients (median age 12.4 years, IQR: 7.9-16.1) with acute leukemia who received peripheral blood allogenic HSCT after radiation-free myeloablative conditioning regimen, in pediatric cell therapy department of Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Tehran, Iran, between December 2014 and December 2021. Associations between risk factors and outcomes were examined by univariable and multivariable logistic regression models. RESULTS A total of 46 patients (23%) had developed HC during the study period. The median onset of HC was 29 (IQR: 24-37) days post-transplant, and it persisted for a median of 33 (7-270) days. The incidence of HC in our patients was estimated to be 3 in 1000 cases (95% CI: 2-4). The results of multivariable logistic model shows that the chance of HC in T-cell acute lymphoblastic leukemia (ALL) compared to B-cell All is nearly five times more (OR = 4.88; 95%CI: (1.51-15.78), P = 0.008). The incidence of HC in patients who underwent HSCT from haploidentical donors was significantly higher than full matched donors (P < 0.001). Undergoing transplant from a matched unrelated and haploidentical donor both augment the chance of HC in about six times more than matched related donors (OR = 6.36; 95%CI: (1.58-25.49), P = 0.009 and OR = 5.7; 95%CI: (1.83-17.75), P = 0.003, respectively). In patients who developed HC compared to non-HC group, overall survival was much worse (P < 0.001). DISCUSSION Most studies have failed to demonstrate any relationship between late-onset HC and the dose of cyclophosphamide. In our study, although the dose of cyclophosphamide was similar in HSCT from MRD and MUD, the hazard of HC incidence was significantly higher in the latter group. This could be accredited to ATG, as in patients in the MRD group who had not received any ATG, the incidence of HC was much lower than the patients who had underwent HSCT from MUD or haploidentical donor group. CONCLUSIONS Patients with T-cell ALL and those who under haploidentical HSCT had the highest incidence of HC.
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Affiliation(s)
- Tahereh Rostami
- Department of Pediatric Cell Therapy, Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Sohrab Aghabeigi
- Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Azadeh Kiumarsi
- Department of Pediatric Cell Therapy, Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Amir Kasaeian
- Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran; Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mehdi Kardoust Parizi
- Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Urology, Medical University of Vienna, Vienna, Austria.
| | - Amirhosein Mirhosseini
- Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Mohammad Reza Rostami
- Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Davoud Babakhani
- Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Farnaz Tavakoli
- Department of Nephrology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
| | - Ghasem Janbabai
- Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Seied Asadollah Mousavi
- Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Shariati Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
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Voisot A, Triffaux F, Roland I, Meex C, Detrembleur N, Baron F, Willems E, David W, Beguin Y, Servais S. Endovesical instillation of Cidofovir in the treatment of BK polyomavirus hemorrhagic cystitis after allogeneic hematopoietic cell transplantation. Curr Res Transl Med 2023; 71:103366. [PMID: 36427417 DOI: 10.1016/j.retram.2022.103366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 08/04/2022] [Accepted: 09/19/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hemorrhagic cystitis (HC) with BK polyomavirus (BKPyV) is a common complication after allogeneic hematopoietic cell transplantation (alloHCT) that may lead to severe discomfort for the patient and significant morbidity (urinary obstruction, increased transfusion requirements and prolonged hospitalization). So far, there is no clear consensus on how to manage this complication. PATIENTS AND METHODS Here, we report a single-center case series of 9 patients (4 children and 5 adults) treated with cidofovir endovesical (EV) instillation(s) for BKPyV-HC after alloHCT. EV Cidofovir was administered at a dose of 5 mg/kg, for 1 to 3 instillations (with a minimum delay between 2 successive doses of 5 days). RESULTS Eight out of the 9 treated patients with EV Cidofovir achieved a complete resolution of HC after 1-3 instillation(s), without recurrence of symptomatic infection within the next 3 months. Only 1 adult patient did not improve after treatment and developed severe morbidity (emphysematous cystitis). CONCLUSION Although this single-center case series of EV cidofovir for BKPyV HC after alloHCT shows encouraging results, only large prospective studies will definitively establish the effectiveness of this therapy.
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Affiliation(s)
- Adrien Voisot
- Department of Clinical Hematology, University Hospital of Liège, CHU Sart-Tilman, 4000 Liège, Belgium
| | - François Triffaux
- Department of Urology, University Hospital of Liège, CHU Sart-Tilman, 4000 Liège, Belgium
| | - Isabelle Roland
- Department of Pharmacy, University Hospital of Liège, CHU Sart-Tilman, 4000 Liège, Belgium
| | - Cecile Meex
- Laboratory of Microbiology, University Hospital of Liège, CHU Sart-Tilman, 4000 Liège, Belgium
| | - Nancy Detrembleur
- Department of Pathology, University Hospital of Liège, CHU Sart-Tilman, 4000 Liège, Belgium
| | - Fréderic Baron
- Department of Clinical Hematology, University Hospital of Liège, CHU Sart-Tilman, 4000 Liège, Belgium; Hematology Research Unit GIGA-I3, University of Liège, CHU Sart-Tilman, 4000 Liège, Belgium
| | - Evelyne Willems
- Department of Clinical Hematology, University Hospital of Liège, CHU Sart-Tilman, 4000 Liège, Belgium
| | - Waltregny David
- Department of Urology, University Hospital of Liège, CHU Sart-Tilman, 4000 Liège, Belgium
| | - Yves Beguin
- Department of Clinical Hematology, University Hospital of Liège, CHU Sart-Tilman, 4000 Liège, Belgium; Hematology Research Unit GIGA-I3, University of Liège, CHU Sart-Tilman, 4000 Liège, Belgium
| | - Sophie Servais
- Department of Clinical Hematology, University Hospital of Liège, CHU Sart-Tilman, 4000 Liège, Belgium; Hematology Research Unit GIGA-I3, University of Liège, CHU Sart-Tilman, 4000 Liège, Belgium.
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Lionel S, Abraham A, Mathews V, Lakshmi K, Abraham A, George B. BK polyomavirus hemorrhagic cystitis in hematopoietic cell transplant recipients. J Glob Infect Dis 2022; 14:17-23. [PMID: 35418731 PMCID: PMC8996450 DOI: 10.4103/jgid.jgid_139_21] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 09/23/2021] [Accepted: 09/30/2021] [Indexed: 12/03/2022] Open
Abstract
Introduction: BK polyomavirus-associated hemorrhagic cystitis (BKPyV-HC) is a well-recognized infective complication of hematopoietic cell transplant (HCT) with increased organ dysfunction and mortality. This study was performed to describe the local incidence, risk factors, and outcomes of BKPyV infection. Methods: This retrospective case–control study was conducted between 2007 and 2016 from a tertiary hospital in South India. We identified HCT recipients diagnosed with BKPyV-HC and compared them with recipients over the same period who did not develop BK virus infection matched for age, sex, diagnosis, and donor type. We collected data from central electronic medical records and databases maintained in the departments of hematology and virology. Results: Over the study period, 1276 transplants were performed, of which 262 patients (20.5%) developed HC and 105 (8.2%) were BKPyV-positive. Grade 3 HC was most commonly (57.1%) seen, and the median time to develop BKPyV-HC was 35 (range 0–858) days. Survival was significantly lower in the cases (42.9% vs. 61%, P < 0.05). On univariate analysis, the protective effect of nonmyeloablative conditioning (P = 0.04), residual disease at the time of transplant in malignant conditions (P = 0.001), lower CD34 dose (P = 0.006), presence of acute graft versus host disease (GVHD, P < 0.001), reactivation of cytomegalovirus infection (P < 0.001), and presence of bacterial urinary tract infection (UTI) (P < 0.001) were significant factors. Multivariate logistic regression confirmed the presence of acute GVHD (P = 0.041), bacterial UTI (P < 0.001), and residual disease (P = 0.009) at HCT as significant risk factors for BKPyV-HC. Conclusions: Our study affirms the homogeneity of BKPyV-HC disease in low- and middle-income HCT settings with prior reports and the need for therapeutic strategies to reduce its resultant mortality.
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Gupta S, Portales-Castillo I, Daher A, Kitchlu A. Conventional Chemotherapy Nephrotoxicity. Adv Chronic Kidney Dis 2021; 28:402-414.e1. [PMID: 35190107 DOI: 10.1053/j.ackd.2021.08.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 08/06/2021] [Accepted: 08/09/2021] [Indexed: 12/27/2022]
Abstract
Conventional chemotherapies remain the mainstay of treatment for many malignancies. Kidney complications of these therapies are not infrequent and may have serious implications for future kidney function, cancer treatment options, eligibility for clinical trials, and overall survival. Kidney adverse effects may include acute kidney injury (via tubular injury, tubulointerstitial nephritis, glomerular disease and thrombotic microangiopathy), long-term kidney function loss and CKD, and electrolyte disturbances. In this review, we summarize the kidney complications of conventional forms of chemotherapy and, where possible, provide estimates of incidence, and identify risk factors and strategies for kidney risk mitigation. In addition, we provide recommendations regarding kidney dose modifications, recognizing that these adjustments may be limited by available supporting pharmacokinetic and clinical outcomes data. We discuss management strategies for kidney adverse effects associated with these therapies with drug-specific recommendations. We focus on frequently used anticancer agents with established kidney complications, including platinum-based chemotherapies (cisplatin, carboplatin, oxaliplatin), cyclophosphamide, gemcitabine, ifosfamide, methotrexate and pemetrexed, among others.
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Palacio D, Prakash K, Riedel DJ. Review of Intravesicular Cidofovir for BK Virus Hemorrhagic Cystitis. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2021. [DOI: 10.1007/s40506-021-00251-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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BK virus-specific T-cell immune reconstitution after allogeneic hematopoietic cell transplantation. Blood Adv 2021; 4:1881-1893. [PMID: 32374880 DOI: 10.1182/bloodadvances.2019001120] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 03/26/2020] [Indexed: 12/13/2022] Open
Abstract
Clinical disease caused by BK virus reactivation is a frequent complication of allogeneic hematopoietic cell transplantation (HCT). Because of the lack of effective antiviral agents, BK virus-specific T cells are emerging as a potential therapy for BK virus disease, but the immune response to BK virus after allogeneic HCT has not been well characterized. Our study describes reconstitution of BK virus-specific T-cell immunity in 77 adult patients after HCT. All patients had urinary symptoms, and urine was tested for BK virus replication; 33 patients were positive for BK virus (cases), and 44 were negative (controls). In BK virus cases, the median time to first positive test was 75 days (range, 2-511). BK virus cases had lower CD4 T-cell counts 3 to 9 months after transplant, but CD8 T-cell counts were similar in cases and controls. BK virus-specific T cells were identified by cytokine flow cytometry in cryopreserved samples collected prospectively. BK virus-specific CD4 T cells producing T helper 1 (Th1) cytokines recovered quickly after HCT. BK virus-specific T cells were detected more frequently in patients with BK virus reactivation at most time points, and CD4 T cells producing Th1 cytokines were more frequent than BK virus-specific cytolytic CD8 T cells. Early detection of interferon-γ+ and cytolytic BK virus-specific CD4 T cells was associated with lower rates of hematuria among cases. Overall, our study describes recovery of BK virus-specific T cells after HCT and the distinct roles for BK virus-specific T cells in the development and resolution of clinical symptoms.
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Yazısız H, Uygun V, Çolak D, Mutlu D, Hazar V, Öğünç D, Öngüt G, Küpesiz FT. Incidence of BKV in the urine and blood samples of pediatric patients undergoing HSCT. Pediatr Transplant 2021; 25:e13894. [PMID: 33136312 DOI: 10.1111/petr.13894] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 08/20/2020] [Accepted: 09/28/2020] [Indexed: 11/27/2022]
Abstract
The aims were to investigate the incidence of BKV infection and the presence of HC in pediatric patients undergoing HSCT. Twenty-four children patients (M/F: 17/7) undergoing HSCT in a single center over a period of 1 year were included in the study. The presence of BKV DNA was determined by quantitative real-time PCR in plasma and urine samples at the following times: before transplantation, twice a week until engraftment time, and weekly for + 100 days. The mean age of the patients was 7.79 ± 5.03 years, the mean follow-up time was 95.6 ± 25.9 days, and the average number of samples per patient was 15.8 ± 3.2. BKV DNA was detected in at least one urine sample in 91.6% (n: 22) and at least one plasma sample in 75% (n:18) of the patients. The median time to the first BKV DNA positivity in urine and plasma samples was 11 (range: 1-80) and 32 days (range: 2-79), respectively. The median value of BKV DNA copies in urine and plasma were 1.7 × 106 (range: 2.8 × 101 -1.2 × 1014 ) and 1.9 × 103 copies/mL (range: 3-2.1 × 106 ), respectively. Thirteen patients (54.2%) had hematuria with BKV viruria; 8 (33.3%) patients had viremia. The median value of the BKV DNA copies in urine and plasma was 4.4 × 107 (range: 65-1 × 1011 ) and 2.9 × 103 (range: 7-7.8 × 104 ) copies/mL in these patients. Two (15.4%) of the 13 patients with BKV viruria and hematuria were diagnosed with BKV-related HC. BKV DNA viral load monitoring of urine and plasma in pediatric HSCT patients with a high risk for viral infections is valuable for understanding the development of BKV-related HC.
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Affiliation(s)
- Hatice Yazısız
- Department of Medical Microbiology, Akdeniz University Medical Faculty, Antalya, Turkey
| | - Vedat Uygun
- Department of Pediatric Hematology & Oncology, Medical Park Antalya Hospital, Antalya, Turkey
| | - Dilek Çolak
- Department of Medical Microbiology, Akdeniz University Medical Faculty, Antalya, Turkey
| | - Derya Mutlu
- Department of Medical Microbiology, Akdeniz University Medical Faculty, Antalya, Turkey
| | - Volkan Hazar
- Department of Pediatric Hematology & Oncology, MSG Medstar Yıldız Hospital, Antalya, Turkey
| | - Dilara Öğünç
- Department of Medical Microbiology, Akdeniz University Medical Faculty, Antalya, Turkey
| | - Gözde Öngüt
- Department of Medical Microbiology, Akdeniz University Medical Faculty, Antalya, Turkey
| | - Funda Tayfun Küpesiz
- Department of Pediatric Hematology & Oncology, Akdeniz University Medical Faculty, Antalya, Turkey
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Superselective Vesical Artery Embolization for Intractable Hemorrhagic Cystitis Following Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Study in 26 Patients. Cardiovasc Intervent Radiol 2021; 44:943-951. [PMID: 33608760 DOI: 10.1007/s00270-021-02786-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 01/23/2021] [Indexed: 10/22/2022]
Abstract
PURPOSE To evaluate the safety and efficacy of superselective vesical artery embolization (SVAE) in the treatment of intractable hemorrhagic cystitis (HC) following hematopoietic stem cell transplantation (HSCT). METHODS From January 2010 to December 2018, 26 patients with hematologic malignancy who underwent SVAE for treatment of intractable HC following HSCT were retrospectively reviewed. SVAE was performed with 300-500 μm gelatin-sponge particles initially. Technical success was defined as achieving bilateral SVAE for all the prominent vesical arteries. Therapeutic efficacy was defined as: Complete response (CR): macroscopic hematuria completely disappeared on more than 2 consecutive days after SVAE; Partial response (PR): macroscopic hematuria reduced after SVAE or briefly disappeared after SVAE but reappeared soon within 2 days; No response: no response to SVAE or hematuria aggravated after SVAE; Recurrence: macroscopic hematuria relapsed on follow-up after achieving an initial CR. Adverse events were also registered. RESULTS There was a mean follow-up of 11.4 months (range, 0.5-83.7). The mean interval for the onset of HC after HSCT was 39.7 ± 19.0 days, and mean duration of hematuria before embolization was 14.9 ± 15.7 days. SVAE was technically successful in all patients. After embolization, macroscopic hematuria regressed within 48 h for all patients. The mean urine erythrocyte counts dropped from 14,213.2 ± 20,999.0/uL before SVAE to 6072.9 ± 12,720.7/uL on 3d after SVAE (P = 0.002) and 3720.2 ± 8988.9/uL on 7 d after SVAE (P = 0.001), respectively. Hematuria completely disappeared prior to discharge in 23 (88.5%) patients (including 20 with one embolization and 3 with 2 embolizations) and remainder 3 patients had PR. No major procedure-related complications were noted, except for post-embolization syndrome in 8 patients, which resolved with symptomatic treatment. On follow-up monthly, hematuria recurrence was seen in 4/23 patients (17.4%) and was managed conservatively in 2 patients and with repeat embolization in the remainder 2 patients. CONCLUSION For fragile patients with hematologic malignancy, SVAE is safe and effective to treat HC following HSCT, even though repeat embolization may be required to achieve a sustained complete remission of the hematuria.
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Jandial A, Mishra K, Sandal R, Kant Sahu K. Management of BK virus-associated haemorrhagic cystitis in allogeneic stem cell transplant recipients. Ther Adv Infect Dis 2021; 8:2049936121991377. [PMID: 33614030 PMCID: PMC7871057 DOI: 10.1177/2049936121991377] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 01/04/2021] [Indexed: 12/18/2022] Open
Abstract
BK virus (BKV)-related haemorrhagic cystitis (HC) is an important cause of morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). The various risk factors include high-level BKV viruria and/or viremia, myeloablative conditioning, acute graft versus host disease (GVHD), cytomegalovirus viremia, and unrelated or HLA-mismatched donor. The presence of high plasma BK viral load and cytopenias have been implicated as important predictors for protracted disease course. These patients frequently require hospitalisation which may extend for several weeks. Supportive measures in the form of analgesics, intravenous hydration, bladder irrigation, and transfusion support remain the mainstay of management. Various drugs have been used with limited success in this setting. These include antiviral drugs, fluoroquinolones, leflunomide, growth factors, clotting factors, estrogens, and prostaglandins. The role of adoptive cellular immunotherapy has also been explored but lacks clinical validation. The strategies aimed at expediting urothelial repair like hyperbaric oxygen therapy (HBOT), intravesical fibrin glue and platelet-rich plasma (PRP) are emerging. Some patients with severe disease do require surgical intervention to relieve urinary obstruction. The frequent co-occurrence of acute GVHD and CMV disease further complicates the management in such patients. There is an unmet need for effective and evidence-based options for the prevention and management of this disease. Due to lack of robust data supported by randomised trials, the acceptability of the available guidelines to simplify the treatment is expected to be low. Despite the availability of various treatment options, the management of BKV-related HC in day-to-day practice continues to be a challenge. The aim of this article is to put forward an up-to-date review of the preventive and therapeutic strategies for BKV-related HC.
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Affiliation(s)
- Aditya Jandial
- Department of Internal Medicine (Adult Clinical Hematology Division), Postgraduate Institute of Medical Education and Research, Chandigarh (Union Territory), India
| | - Kundan Mishra
- Department of Clinical Hematology and Stem Cell Transplant, Army Hospital (Research & Referral) New Delhi, India
| | - Rajeev Sandal
- Department of Radiotherapy and Oncology, Indira Gandhi Medical College Shimla, Himachal Pradesh, India
| | - Kamal Kant Sahu
- Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA 01608, USA
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Prezioso C, Van Ghelue M, Moens U, Pietropaolo V. HPyV6 and HPyV7 in urine from immunocompromised patients. Virol J 2021; 18:24. [PMID: 33482864 PMCID: PMC7821732 DOI: 10.1186/s12985-021-01496-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 01/12/2021] [Indexed: 12/20/2022] Open
Abstract
Background Human polyomavirus 6 (HPyV6) and HPyV7 are two of the novel polyomaviruses that were originally detected in non-diseased skin. Serological studies have shown that these viruses are ubiquitous in the healthy adult population with seroprevalence up to 88% for HPyV6 and 72% for HPyV7. Both viruses are associated with pruritic skin eruption in immunocompromised patients, but a role with other diseases in immunoincompetent patients or malignancies has not been established. Methods PCR was used to determine the presence of HPyV6 and HPyV7 DNA in urine samples from systemic lupus erythematosus (n = 73), multiple sclerosis (n = 50), psoriasis vulgaris (n = 15), arthritic psoriasis (n = 15) and HIV-positive patients (n = 66). In addition, urine from pregnant women (n = 47) and healthy blood donors (n = 20) was investigated. Results HPyV6 DNA was detected in 21 (28.8%) of the urine specimens from SLE patients, in 6 (9.1%) of the urine samples from the HIV-positive cohort, and in 19 (40.4%) samples from pregnant women. HPyV7 DNA was only found in 6 (8.2%) of the urine specimens from SLE patients and in 4 (8.5%) samples from pregnant women. No HPyV6 and HPyV7 viruria was detected in the urine samples from the other patients. Conclusions HPyV6, and to a lesser extend HPyV7, viruria seems to be common in SLE and HIV-positive patients, and pregnant women. Whether these viruses are of clinical relevance in these patients is not known.
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Affiliation(s)
- Carla Prezioso
- Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy.,Microbiology of Chronic Neuro-Degenerative Pathologies, IRCSS San Raffaele Pisana, Rome, Italy
| | - Marijke Van Ghelue
- Department of Medical Genetics, Division of Child and Adolescent Health, University Hospital of North Norway, Tromsø, Norway.,Department of Clinical Medicine Faculty of Health Sciences, University of Tromsø - The Arctic University of Norway, Tromsø, Norway
| | - Ugo Moens
- Department of Medical Biology, Faculty of Health Sciences, University of Tromsø - The Arctic University of Norway, Tromsø, Norway.
| | - Valeria Pietropaolo
- Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy.
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Onda Y, Kanda J, Hanaoka N, Watanabe M, Arai Y, Hishizawa M, Kondo T, Yamashita K, Nagao M, Fujimoto T, Takaori-Kondo A. Possible nosocomial transmission of virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Ann Hematol 2021; 100:753-761. [PMID: 33439306 DOI: 10.1007/s00277-021-04414-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 01/06/2021] [Indexed: 12/01/2022]
Abstract
Adenovirus (ADV)- or BK virus (BKV)-associated hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several risk factors have been previously reported; however, it is unclear whether virus-associated HC can be transmitted. To clarify this point, we performed a retrospective cohort study on 207 consecutive patients who underwent allo-HSCT at Kyoto University Hospital between 2012 and 2018. We evaluated the incidence and risk factors of virus-associated HC and performed a phylogenetic analysis of the ADV partial sequence. The median age at transplantation was 50 (range, 17-68) years. Fifty-eight patients (28%) developed HC. ADVs were detected in 18 cases, BKVs were detected in 51, both were detected in 12, and only John Cunningham virus (JCV) was detected in 1 case. No factor was significantly associated with HC. However, both ADV- and BKV-HC occurred intensively between April 2016 and September 2017, which suggested possible nosocomial transmission of ADV and BKV. Genome sequencing of the hexon, E3, and penton regions of detected ADVs identified 7 cases of ADV type 11, 2 cases of type 35, and 3 cases of a type 79-related strain. A sequence analysis revealed that these strains in each type were almost identical, except for one case of a type 79-related strain. In conclusion, ADV-HCs with possible nosocomial transmission were described based on genotyping of the virus and partial sequencing of the viral genome. Although viral HC after allo-HSCT is thought to mainly be due to reactivation of a latent virus, nosocomial transmission of ADV or BKV should also be considered.
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Affiliation(s)
- Yoshiyuki Onda
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Junya Kanda
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Nozomu Hanaoka
- Center for Infectious Disease Risk Management, National Institute of Infectious Diseases, Tokyo, Japan
| | - Mizuki Watanabe
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Yasuyuki Arai
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Masakatsu Hishizawa
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Tadakazu Kondo
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Kouhei Yamashita
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Miki Nagao
- Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tsuguto Fujimoto
- Center for Infectious Disease Risk Management, National Institute of Infectious Diseases, Tokyo, Japan
| | - Akifumi Takaori-Kondo
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
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Bush R, Johns F, Betty Z, Goldstein S, Horn B, Shoemaker L, Upadhyay K. BK virus encephalitis and end-stage renal disease in a child with hematopoietic stem cell transplantation. Pediatr Transplant 2020; 24:e13739. [PMID: 32412694 DOI: 10.1111/petr.13739] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 03/09/2020] [Accepted: 04/20/2020] [Indexed: 01/07/2023]
Abstract
BK virus encephalitis after HSCT is uncommon. Several reports of native kidney BKVN in patients with HSCT, hematologic malignancies, human immunodeficiency virus infection, and non-renal solid organ transplantation have been described. However, an uncommon combination of BK encephalitis and ESRD of native kidneys secondary to BK virus in a child with HSCT has not been described. We report a 10-year-old boy who presented with a gradually rising serum creatinine during treatment for severe autoimmune hemolytic anemia, which he developed 9 months after receiving an allogeneic HSCT for aplastic anemia. There was no proteinuria or hematuria present. Serum BK virus load was 5 × 106 copies/mL. A renal biopsy showed evidence of BKVN. He developed fever, seizures, and confusion, and the (CSF) showed significant presence of the BK virus (1 × 106 copies/mL) along with biochemical evidence of viral encephalitis. Cerebrospinal fluid cultures were negative. Despite significant clinical symptoms and presence of BK virus in CSF, the magnetic resonance brain imaging findings were minimal. With reduction of immunosuppression, there was resolution of BK encephalitis but BKVN remained resistant to multiple anti-BK virus agents, including leflunomide and cidofovir. He eventually became dialysis-dependent and, 6 years later, received a renal transplant from his mother. This case illustrates that BK virus in severely immunocompromised HSCT recipient may lead to BK encephalitis and BKVN of native kidneys, even without hemorrhagic cystitis, leading to ESRD. Knowledge of such is important for appropriate timely evaluation and management.
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Affiliation(s)
- Rachel Bush
- Division of Pediatric Nephrology, Department of Pediatrics, University of Florida, Gainesville, FL, USA
| | - Felicia Johns
- Division of Pediatric Nephrology, Department of Pediatrics, University of Florida, Gainesville, FL, USA
| | - Zachary Betty
- Division of Pediatric Nephrology, Department of Pediatrics, University of Florida, Gainesville, FL, USA
| | - Steven Goldstein
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA
| | - Biljana Horn
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Florida, Gainesville, FL, USA
| | - Lawrence Shoemaker
- Division of Pediatric Nephrology, Department of Pediatrics, University of Florida, Gainesville, FL, USA
| | - Kiran Upadhyay
- Division of Pediatric Nephrology, Department of Pediatrics, University of Florida, Gainesville, FL, USA
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Atilla E, Ateş C, Uslu A, Ataca Atilla P, Dolapçı I, Tekeli A, Topçuoğlu P. Prospective Analysis of Hemorrhagic Cystitis and BK Viremia in Allogeneic Hematopoietic Stem Cell Transplantation. Turk J Haematol 2020; 37:186-192. [PMID: 31852035 PMCID: PMC7463211 DOI: 10.4274/tjh.galenos.2019.2019.0296] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 12/18/2019] [Indexed: 02/07/2023] Open
Abstract
Objective BK virus (BKV) infection has been shown to be related to hemorrhagic cystitis (HC) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). There are conflicting data regarding the association between BKV titers in plasma and clinical disease as well as the risk factors for BKV-related HC. Our aim is to study the risk factors and relationship with plasma BK viral load for development of HC in a prospective analysis. Materials and Methods We prospectively evaluated 59 patients who received allo-HSCT between 2014 and 2016 by quantitative BK virus polymerase chain reaction (PCR) (Altona Diagnostics, Germany) from blood samples at days 0, 30, 60, and 90 after allo-HSCT. The patients were monitored for signs and symptoms of HC. Results HC was diagnosed in 22 patients (37%) at a mean of 100 days (range: 0-367 days). In multivariate analysis, the usage of cyclophosphamide (sub-distribution hazard ratio [sdHR]: 7.82, confidence interval [CI]: 1.375-39.645, p=0.02), reactivated CMV (sdHR: 6.105, CI: 1.614-23.094, p=0.008), and positive BKV viremia (sdHR: 2.15, CI: 1.456-22.065, p=0.01) significantly increased the risk of developing HC. Patients with higher viral loads at day 30 and day 60 were diagnosed with more severe HC (p<0.001). Median BK viral loads of >101.5 copies/mL at day 0 (sensitivity 0.727, specificity 0.875), >98.5 copies/mL at day 30 (sensitivity 0.909, specificity 0.875), and >90.0 copies/mL at day 60 (sensitivity 0.909, specificity 0.875) were indicative of HC. Conclusion Our study showed that administration of cyclophosphamide, CMV reactivation, and BK virus positivity were associated with HC. Plasma BK virus PCR titers at days 0, 30, and 60 after transplant were sensitive tools for predicting clinically proven HC.
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Affiliation(s)
- Erden Atilla
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Can Ateş
- Van Yüzüncü Yıl University Faculty of Medicine, Department of Biostatistics, Van, Turkey
| | - Atilla Uslu
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Pınar Ataca Atilla
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Istar Dolapçı
- Ankara University Faculty of Medicine, Department of Microbiology, Ankara, Turkey
| | - Alper Tekeli
- Ankara University Faculty of Medicine, Department of Microbiology, Ankara, Turkey
| | - Pervin Topçuoğlu
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
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21
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Ito Y, Hino T, Honda A, Kurokawa M. Fluoroquinolones for BK viral complication after transplantation: Meta-analysis. Transpl Infect Dis 2020; 22:e13433. [PMID: 32744404 DOI: 10.1111/tid.13433] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 07/24/2020] [Accepted: 07/24/2020] [Indexed: 12/15/2022]
Abstract
OBJECTIVES BK polyomavirus (BKV) causes two distinct complications after transplantation, hemorrhagic cystitis (BKV-HC) after hematopoietic stem cell transplantation (HSCT), and BKV-associated nephropathy (BKVAN) after kidney transplantation (KT). Although fluoroquinolones show efficacy against BKV proliferation in vitro, the clinical effect remains uncertain; thus, we performed meta-analysis to assess its efficacy in the prophylaxis. METHODS Articles published before March 2020 were searched from PubMed, the Cochrane Library, ISRCTN registry, and ClinicalTrials.gov. Primary outcomes were BKV-HC after HSCT and BKVAN after KT. Secondary outcomes were BK viremia, viruria after KT, and fluoroquinolone-related adverse events. RESULTS Three trials with 281 patients post-HSCT and 11 trials with 1882 patients post KT were included as for prophylaxis. Fluoroquinolone prophylaxis did not show effects on BKV-HC (OR 0.54, 95% CI 0.13-2.25), BKVAN (OR 0.74, 95% CI 0.35-1.55), and BK viremia (OR 0.79, 95% CI 0.49-1.28), but significantly decreased BK viruria (OR 0.64, 95% CI 0.45-0.91). Fluoroquinolone prophylaxis was associated with the higher percentage of fluoroquinolone-resistant infection among identified bacteria (OR 2.38, 95% CI 1.16-4.88), but the incidence of fluoroquinolone-resistant infection was similar (OR 1.15, 95% CI 0.71-1.86), due to the decrease of infection itself (OR 0.52, 95% CI 0.34-0.81). CONCLUSIONS This meta-analysis showed that fluoroquinolones did not prevent BKV-HC after HSCT or BKVAN after KT, although the effect against BKV-HC should be further investigated by randomized controlled trials. Fluoroquinolones could reduce the rate of BK viruria to some extent but may not have clinically sufficient effects.
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Affiliation(s)
- Yusuke Ito
- Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Bunkyo City, Japan
| | - Toshiya Hino
- Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Bunkyo City, Japan
| | - Akira Honda
- Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Bunkyo City, Japan
| | - Mineo Kurokawa
- Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Bunkyo City, Japan.,Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, Bunkyo City, Japan
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22
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Santos CAQ, Rhee Y, Czapka MT, Kazi AS, Proia LA. Make Sure You Have a Safety Net: Updates in the Prevention and Management of Infectious Complications in Stem Cell Transplant Recipients. J Clin Med 2020; 9:jcm9030865. [PMID: 32245201 PMCID: PMC7141503 DOI: 10.3390/jcm9030865] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 03/11/2020] [Indexed: 12/11/2022] Open
Abstract
Hematopoietic stem cell transplant recipients are at increased risk of infection and immune dysregulation due to reception of cytotoxic chemotherapy; development of graft versus host disease, which necessitates treatment with immunosuppressive medications; and placement of invasive catheters. The prevention and management of infections in these vulnerable hosts is of utmost importance and a key “safety net” in stem cell transplantation. In this review, we provide updates on the prevention and management of CMV infection; invasive fungal infections; bacterial infections; Clostridium difficile infection; and EBV, HHV-6, adenovirus and BK infections. We discuss novel drugs, such as letermovir, isavuconazole, meropenem-vaborbactam and bezlotoxumab; weigh the pros and cons of using fluoroquinolone prophylaxis during neutropenia after stem cell transplantation; and provide updates on important viral infections after hematopoietic stem cell transplant (HSCT). Optimizing the prevention and management of infectious diseases by using the best available evidence will contribute to better outcomes for stem cell transplant recipients, and provide the best possible “safety net” for these immunocompromised hosts.
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23
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Tong J, Liu H, Zheng C, Zhu X, Tang B, Wan X, Yao W, Song K, Zhang L, Zhang X, Sun Z. Effects and long-term follow-up of using umbilical cord blood-derived mesenchymal stromal cells in pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis after unrelated cord blood transplantation. Pediatr Transplant 2020; 24:e13618. [PMID: 31944495 DOI: 10.1111/petr.13618] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 10/27/2019] [Accepted: 11/07/2019] [Indexed: 01/05/2023]
Abstract
This is a retrospective study to evaluate the efficacy and safety of umbilical cord blood-derived mesenchymal stromal cells (MSCs) for the treatment of pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis (BKV-HC) after unrelated cord blood transplantation (UCBT). Thirteen pediatric patients with severe BKV-HC from December 2013 to December 2015 were treated with MSCs. The number of MSCs transfused in each session was 1 × 106 /kg once a week until the symptoms improved. The median follow-up time was 1432 (89-2080) days. The median frequency of MSC infusion was 2 (1-3), with eight cured cases and five effective cases; the total efficacy rate was 100%. The copy number of urine BKV DNA was 4.43 (0.36-56.9) ×108 /mL before MSC infusion and 2.67 (0-56.3) ×108 /mL after MSC infusion; the difference was not significant (P = .219). There were no significant differences in the overall survival, disease-free survival, and the incidence of relapse and acute and chronic graft-versus-host disease between the MSC infusion group and non-MSC infusion group. There was also no significant difference in the cytomegalovirus, Epstein-Barr virus (EBV), and fungal and bacterial infection rates between the two groups. Although umbilical cord blood-derived MSCs do not reduce the number of BKV DNA copies in the urine, the cells have a high efficacy rate and minimal side effects in treating severe BKV-HC after UCBT among pediatric patients. MSCs do not affect the rates of relapse, long-term infection, or survival of patients with leukemia.
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Affiliation(s)
- Juan Tong
- Department of Hematology of Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - HuiLan Liu
- Department of Hematology of Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - ChangCheng Zheng
- Department of Hematology of Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - XiaoYu Zhu
- Department of Hematology of Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - BaoLin Tang
- Department of Hematology of Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Xiang Wan
- Department of Hematology of Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Wen Yao
- Department of Hematology of Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - KaiDi Song
- Department of Hematology of Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Lei Zhang
- Department of Hematology of Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - XuHan Zhang
- Department of Hematology of Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - ZiMin Sun
- Department of Hematology of Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
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24
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Impact of extended infusional mesna prophylaxis on the incidence of BK viruria and hemorrhagic cystitis following post-transplantation cyclophosphamide and CTLA4Ig-based haploidentical transplantation. Ann Hematol 2020; 99:839-845. [PMID: 32025839 DOI: 10.1007/s00277-020-03930-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 01/18/2020] [Indexed: 12/19/2022]
Abstract
Hemorrhagic cystitis (HC) has been reported with increased frequency following post-transplantation cyclophosphamide (PTCy)-based haploidentical hematopoietic cell transplantation (HCT) along with a strong association with BK viruria. We prospectively evaluated the incidence of BK viruria and HC in 115 patients (median age 20 years, 2-65) undergoing PTCy-based haploidentical HCT with (n = 71) or without (n = 44) CTLA4Ig. HC prophylaxis consisted of a continuous infusion of mesna 30 min prior and 48 h post-PTCy. The overall incidence of BK viruria was 65.7%. None with BK viruria < 104 copies/ml developed clinical symptoms (n = 65). The incidence of BK viruria ≥ 104 copies/ml was 7.1% (n = 8) and 75% developed HC. The incidence of HC was 5.4% at a median of 30 days. Both BK viruria ≥ 104 copies/ml and HC were strongly associated with acute GVHD (p < 0.001). A higher NRM was observed in those with BK viruria ≥ 104 copies/ml, related to GVHD and its complications (41.7% vs 12.6%, p = 0.04). The incidences of acute GVHD, vis-à-vis, overall BK viruria, BK viruria ≥ 104 copies/ml, and HC, tended to be lower in patients receiving CTLA4Ig. Thus, extended infusional mesna, coupled with significant reduction in alloreactivity along with possible preservation of antiviral immunity associated with the use of CTLA4Ig, was probably responsible for a much lower incidence of BK viruria and resultant HC than reported previously following PTCy-based haploidentical HCT.
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25
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Aldiwani M, Tharakan T, Al-Hassani A, Gibbons N, Pavlu J, Hrouda D. BK Virus Associated Haemorrhagic Cystitis. A systematic review of current prevention and treatment strategies. Int J Surg 2019; 63:34-42. [PMID: 30711618 DOI: 10.1016/j.ijsu.2019.01.019] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 01/29/2019] [Indexed: 12/30/2022]
Abstract
BACKGROUND BK virus is a major cause of late onset haemorrhagic cystitis in patients undergoing Haematopoietic Cell Transplantation (HCT). The evidence for the management of BK Virus Associated Haemorrhagic Cystitis (BKV-HC) is limited. Much of the published data consists of non-randomised case series and case reports. To our knowledge this is the first systematic review for the management of BKV-HC in both paediatric and adult populations. Our primary outcome was to examine the evidence for strategies of 1) prevention and 2) cessation of haematuria associated with BKV. Secondary outcomes were to assess the toxicity of treatment strategies and devise management recommendations for clinicians. MATERIALS AND METHODS We performed a systematic review of the PubMed and Central databases to evaluate the current evidence. A search protocol was prepared and registered with the PROSPERO database (CRD42017082442). The review was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement and AMSTAR (Assessing the methodological quality of systematic reviews) guidelines. Results were classified by treatment type. Qualitative analysis of included articles was performed, and grades of recommendations were devised for each treatment. RESULTS Of 896 titles screened, 44 articles were included for qualitative analysis. The overall quality of evidence was low. There is insufficient evidence to recommend prophylactic quinolones. 40 studies evaluated treatments for established BKV-HC. There are no high-quality comparative studies. Cidofovir is the most studied treatment but quality of evidence is low, and grade of recommendation is weak. Hyperbaric oxygen therapy, Fibrin glue, Leflunomide, Sodium Pentosan Polysulfate, Intravesical Alum and Radiological embolisation have all been described but the effectiveness of these treatments is unclear. CONCLUSION There remains no clear specific treatment for BKV-HC. An effective multi-disciplinary approach leading to early recognition and initiation of treatment is encouraged. The development of novel therapies followed by well-designed clinical studies are urgently needed.
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Affiliation(s)
- M Aldiwani
- Dept of Urology, Imperial College NHS Trust, UK.
| | - T Tharakan
- Dept of Urology, Imperial College NHS Trust, UK
| | - A Al-Hassani
- Dept of Haematology, University College London, UK
| | - N Gibbons
- Dept of Urology, Imperial College NHS Trust, UK
| | - J Pavlu
- Centre for Haematology, Imperial College London, UK
| | - D Hrouda
- Dept of Urology, Imperial College NHS Trust, UK
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26
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Mo XD, Zhang XH, Xu LP, Wang Y, Yan CH, Chen H, Chen YH, Han W, Wang FR, Wang JZ, Liu KY, Huang XJ. Treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: the role of corticosteroids. Ann Hematol 2018. [PMID: 29532160 PMCID: PMC7080199 DOI: 10.1007/s00277-018-3290-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
We aimed to evaluate the treatments, particularly the role of corticosteroids, in patients with late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). One hundred and sixty-three consecutive patients who underwent non-T-cell-depleted allo-HSCT and met the criterion of LOHC after allo-HSCT were enrolled in this study. The median time from allo-HSCT to the occurrence of LOHC was 29 (range, 4–155) days. Pathogens identified in blood and/or urine samples from 143 patients were mostly viruses. All of the patients with LOHC received intravenous fluid hydration, alkalization, and forced diuresis, of which 2 patients achieved complete remission (CR) after these treatments. The remaining 161 patients received anti-infection therapies and 71 achieved CR after the therapies. Corticosteroids were additionally applied to 83 out of 90 patients who did not achieve CR after anti-infection therapies, and 88.0% (n = 73) of them showed a grade 3 to 4 LOHC at the beginning of corticosteroid therapy. Thirty-five patients showed an immediate response (CR or downgraded at least one grade) within 1 week after the beginning of the corticosteroid therapy. Sixty-four patients (77.1%) achieved CR after corticosteroid therapy, and the median period from the beginning of corticosteroid therapy to CR was 17 days. Thus, we observed that viruses were the most common pathogens in LOHC after allo-HSCT and that anti-infection therapies were critical. For patients not showing a satisfactory response to anti-infection therapies, additional corticosteroid therapy may help to achieve CR.
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Affiliation(s)
- Xiao-Dong Mo
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Xiao-Hui Zhang
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Lan-Ping Xu
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Yu Wang
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Chen-Hua Yan
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Huan Chen
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Yu-Hong Chen
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Wei Han
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Feng-Rong Wang
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Jing-Zhi Wang
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Kai-Yan Liu
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Xiao-Jun Huang
- Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China. .,Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
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27
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Atilla E, Yalciner M, Atilla PA, Ates C, Bozdag SC, Yuksel MK, Toprak SK, Gunduz M, Ozen M, Akan H, Demirer T, Arslan O, Ilhan O, Beksac M, Ozcan M, Gurman G, Topcuoglu P. Is cytomegalovirus a risk factor for haemorrhagic cystitis in allogeneic haematopoietic stem cell transplantation recipients? Antivir Ther 2018; 23:647-653. [DOI: 10.3851/imp3252] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2018] [Indexed: 10/28/2022]
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Graf L, Stern M. Acute phase after haematopoietic stem cell transplantation. Hamostaseologie 2017; 32:56-62. [DOI: 10.5482/ha-1176] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2011] [Accepted: 10/07/2011] [Indexed: 01/24/2023] Open
Abstract
SummaryThe transplantation of allogeneic or autologous haematopoietic stem cells is an established treatment for many malignant and non-malignant diseases of the bone marrow. Intensive cytoreductive regimens administered before transplantation induce prolonged and severe cytopenia of all haematopoietic lineages. Thrombocytopenia leads to an increased risk of bleeding, which may be further aggravated by consumption of plasmatic factors as a result of tumour lysis or after antibody administration. At the same time, patients after transplantation are also at increased risk of thrombotic complications. Endothelial damage induced by radio-and chemotherapy, indwelling catheters, prolonged immobilization and a high incidence of systemic infection all contribute to the frequent occurrence of thromboembolic events in this population.This review discusses the incidence and risk factors for haemorrhagic and thrombotic complications after stem cell transplantation. Special emphasis is given to complications occurring specifically in the context of transplantation such as diffuse alveolar haemorrhage, haemorrhagic cystitis, veno-occlusive disease, and transplant associated microangiopathy.
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Park SS, Kwak DH, Jeon YW, Yoon JH, Lee SE, Cho BS, Eom KS, Kim YJ, Kim HJ, Lee S, Min CK, Cho SG, Kim DW, Min WS, Lee JW. Beneficial Role of Low-Dose Antithymocyte Globulin in Unrelated Stem Cell Transplantation for Adult Patients with Acquired Severe Aplastic Anemia: Reduction of Graft-versus-Host Disease and Improvement of Graft-versus-Host Disease-Free, Failure-Free Survival Rate. Biol Blood Marrow Transplant 2017; 23:1498-1508. [PMID: 28554856 DOI: 10.1016/j.bbmt.2017.05.026] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 05/22/2017] [Indexed: 01/04/2023]
Abstract
Stem cell transplantation (SCT) from an unrelated donor (URD) is often considered in patients with severe aplastic anemia (SAA) whom immunosuppressive therapy failed and matched sibling donor is not available. To reduce the incidence of graft-versus-host disease (GVHD) in URD SCT, introducting antithymocyte globulin (ATG) into the conditioning regimen has been proposed. Although ATG was shown to play a role in reducing GVHD in a cohort with diverse hematologic diseases, its role in SAA remains uncertain. The aim of this study was to determine the efficacy and toxicity of ATG in URD SCT for adult patients with SAA. We investigated 83 adult patients with SAA who underwent URD SCT between 2003 and 2014. The transplantation strategy consisted of total body irradiation (total 800 cGy) and cyclophosphamide (total 100 mg/kg to 120 mg/kg), followed by tacrolimus and a short-term methotrexate. We divided patients into 2 groups: group 1 (n = 25), which received HLA-matched (8/8) bone marrow (BM) without ATG, and group 2 (n = 58), which received SCT from either an HLA-mismatched donor or peripheral blood (PB). Thereafter, group 2 was subdivided according to ATG use into group 2A (without ATG, n = 26), which served as a historical cohort, and group 2B (with ATG, n = 32). Rabbit ATG (Thymoglobulin; Genzyme-Sanofi, Lyon, France) was used in group 2B at a dose of 2.5 mg/kg. The median age of all patients was 30 years (range, 17 to 59 years). The incidence of GVHD was significantly lower in group 2B than group 2A, as demonstrated by the rate of grade II to IV acute GVHD at day 100 (31.2% versus 61.5%, P = .003) and the rate of chronic GVHD at 3 years (21.9% versus 65.4%, P = .002). The overall survival rates of the 3 groups were similar. However, GVHD-free, failure-free survival (GFFS) was significantly higher in group 2B than group 2A (P = .034). A multivariable model identified use of ATG as an independent factor affecting grades II to IV acute GVHD (hazard ratio [HR], 2.902; 95% confidence interval [CI], 1.417 to 5.942; P = .004), chronic GVHD (HR , 3.005; 95% CI, 1.279 to 7.059; P = .012), and GFFS (HR, 2.363; 95% CI, 1.162 to 4.805; P = .014). Toxicities, including infectious complications, were not different among the 3 groups. In conclusion, low-dose ATG (2.5 mg/kg) can reduce the incidence of acute and chronic GVHD and improve the quality of life in patients with SAA who receive stem cells from either an HLA-mismatched donor or PB; importantly, these benefits are achieved without increased toxicity. Furthermore, ATG can be considered in URD SCT from HLA-matched BM cells.
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Affiliation(s)
- Sung-Soo Park
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dae Hun Kwak
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Young-Woo Jeon
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jae-Ho Yoon
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung-Eun Lee
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Byung-Sik Cho
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki-Seong Eom
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yoo-Jin Kim
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hee-Je Kim
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seok Lee
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chang-Ki Min
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seok-Goo Cho
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dong-Wook Kim
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Woo-Sung Min
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jong Wook Lee
- Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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Uppugunduri CRS, Storelli F, Mlakar V, Huezo-Diaz Curtis P, Rezgui A, Théorêt Y, Marino D, Doffey-Lazeyras F, Chalandon Y, Bader P, Daali Y, Bittencourt H, Krajinovic M, Ansari M. The Association of Combined GSTM1 and CYP2C9 Genotype Status with the Occurrence of Hemorrhagic Cystitis in Pediatric Patients Receiving Myeloablative Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation. Front Pharmacol 2017; 8:451. [PMID: 28744217 PMCID: PMC5504863 DOI: 10.3389/fphar.2017.00451] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Accepted: 06/22/2017] [Indexed: 12/01/2022] Open
Abstract
Hemorrhagic cystitis (HC) is one of the complications of busulfan-cyclophosphamide (BU-CY) conditioning regimen during allogeneic hematopoietic stem cell transplantation (HSCT) in children. Identifying children at high risk of developing HC in a HSCT setting could facilitate the evaluation and implementation of effective prophylactic measures. In this retrospective analysis genotyping of selected candidate gene variants was performed in 72 children and plasma Sulfolane (Su, water soluble metabolite of BU) levels were measured in 39 children following treatment with BU-CY regimen. The cytotoxic effects of Su and acrolein (Ac, water soluble metabolite of CY) were tested on human urothelial cells (HUCs). The effect of Su was also tested on cytochrome P 450 (CYP) function in HepaRG hepatic cells. Cumulative incidences of HC before day 30 post HSCT were estimated using Kaplan–Meier curves and log-rank test was used to compare the difference between groups in a univariate analysis. Multivariate Cox regression was used to estimate hazard ratios with 95% confidence intervals (CIs). Multivariate analysis included co-variables that were significantly associated with HC in a univariate analysis. Cumulative incidence of HC was 15.3%. In the univariate analysis, HC incidence was significantly (p < 0.05) higher in children older than 10 years (28.6 vs. 6.8%) or in children with higher Su levels (>40 vs. <11%) or in carriers of both functional GSTM1 and CYP2C9 (33.3 vs. 6.3%) compared to the other group. In a multivariate analysis, combined GSTM1 and CYP2C9 genotype status was associated with HC occurrence with a hazards ratio of 4.8 (95% CI: 1.3–18.4; p = 0.02). Ac was found to be toxic to HUC cells at lower concentrations (33 μM), Su was not toxic to HUC cells at concentrations below 1 mM and did not affect CYP function in HepaRG cells. Our observations suggest that pre-emptive genotyping of CYP2C9 and GSTM1 may aid in selection of more effective prophylaxis to reduce HC development in pediatric patients undergoing allogeneic HSCT. Article summary: (1) Children carrying functional alleles in GSTM1 and CYP2C9 are at high risk for developing hemorrhagic cystitis following treatment with busulfan and cyclophosphamide based conditioning regimen. (2) Identification of children at high risk for developing hemorrhagic cystitis in an allogeneic HSCT setting will enable us to evaluate and implement optimal strategies for its prevention. Trial registration: This study is a part of the trail “clinicaltrials.gov identifier: NCT01257854.”
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Affiliation(s)
- Chakradhara Rao S Uppugunduri
- Onco-Hematology Unit, Geneva University Hospital, Department of PediatricsGeneva, Switzerland.,CANSEARCH Research Laboratory, Department of Pediatrics, Faculty of Medicine, University of GenevaGeneva, Switzerland
| | - Flavia Storelli
- Clinical Pharmacology and Toxicology Service, Geneva University HospitalGeneva, Switzerland
| | - Vid Mlakar
- Onco-Hematology Unit, Geneva University Hospital, Department of PediatricsGeneva, Switzerland.,CANSEARCH Research Laboratory, Department of Pediatrics, Faculty of Medicine, University of GenevaGeneva, Switzerland
| | - Patricia Huezo-Diaz Curtis
- Onco-Hematology Unit, Geneva University Hospital, Department of PediatricsGeneva, Switzerland.,CANSEARCH Research Laboratory, Department of Pediatrics, Faculty of Medicine, University of GenevaGeneva, Switzerland
| | - Aziz Rezgui
- CHU Sainte-Justine Research Center, Charles-Bruneau Cancer Center, MontrealQC, Canada
| | - Yves Théorêt
- Clinical Pharmacology Unit, CHU Sainte-Justine, MontrealQC, Canada
| | - Denis Marino
- CANSEARCH Research Laboratory, Department of Pediatrics, Faculty of Medicine, University of GenevaGeneva, Switzerland
| | | | - Yves Chalandon
- Division of Hematology, Department of Medical Specialties, Geneva University HospitalGeneva, Switzerland
| | - Peter Bader
- Division for Stem Cell Transplantation and Immunology, University Hospital FrankfurtFrankfurt, Germany
| | - Youssef Daali
- Clinical Pharmacology and Toxicology Service, Geneva University HospitalGeneva, Switzerland
| | - Henrique Bittencourt
- Department of Pediatrics, Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, MontrealQC, Canada
| | - Maja Krajinovic
- CHU Sainte-Justine Research Center, Charles-Bruneau Cancer Center, MontrealQC, Canada.,Clinical Pharmacology Unit, CHU Sainte-Justine, MontrealQC, Canada.,Department of Pediatrics, Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, MontrealQC, Canada
| | - Marc Ansari
- Onco-Hematology Unit, Geneva University Hospital, Department of PediatricsGeneva, Switzerland.,CANSEARCH Research Laboratory, Department of Pediatrics, Faculty of Medicine, University of GenevaGeneva, Switzerland
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Abstract
Similarly to the general population, genitourinary tract infections are common conditions in theimmunocompromised host. They can be furthermore divided into infections of the urinary tract and genital tract infections. Transplant recipients are more likely to have infections of the urinary tract infections while persons with human immunodeficiency virus (HIV) are at higher risk for the second group of infections, especially sexually transmitted infections (STIs). Manifestations of these diseases can be associated with more complications and can be more severe. We provide an overview of manifestations, diagnosis, and management of these disorders.
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Dosin G, Aoun F, El Rassy E, Assi T, Lewalle P, Blanc J, van Velthoven R, Bron D. Viral-induced Hemorrhagic Cystitis After Allogeneic Hematopoietic Stem Cell Transplant. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2017; 17:438-442. [DOI: 10.1016/j.clml.2017.05.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Revised: 02/28/2017] [Accepted: 05/04/2017] [Indexed: 10/19/2022]
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Höller K, Fabeni L, Herling M, Holtick U, Scheid C, Knops E, Lübke N, Kaiser R, Pfister H, Di Cristanziano V. Dynamics of BKPyV reactivation and risk of hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Eur J Haematol 2017; 99:133-140. [DOI: 10.1111/ejh.12895] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2017] [Indexed: 12/20/2022]
Affiliation(s)
| | - Lavinia Fabeni
- National Institute for Infectious Diseases L. Spallanzani - IRCCS; Rome Italy
| | - Marco Herling
- Department I of Internal Medicine; Center for Integrated Oncology (CIO) Köln-Bonn and Excellence Cluster for Cellular Stress Response and Aging-Associated Diseases (CECAD); University Hospital of Cologne; Cologne Germany
| | - Udo Holtick
- Department I of Internal Medicine; Center for Integrated Oncology (CIO) Köln-Bonn and Excellence Cluster for Cellular Stress Response and Aging-Associated Diseases (CECAD); University Hospital of Cologne; Cologne Germany
| | - Christof Scheid
- Department I of Internal Medicine; Center for Integrated Oncology (CIO) Köln-Bonn and Excellence Cluster for Cellular Stress Response and Aging-Associated Diseases (CECAD); University Hospital of Cologne; Cologne Germany
| | - Elena Knops
- Institute of Virology; University of Cologne; Cologne Germany
| | - Nadine Lübke
- Institute of Virology; University of Cologne; Cologne Germany
| | - Rolf Kaiser
- Institute of Virology; University of Cologne; Cologne Germany
| | - Herbert Pfister
- Institute of Virology; University of Cologne; Cologne Germany
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34
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Bladder Rupture After Chronic Hemorrhagic Cystitis in a Stem Cell Transplantation Recipient. Transplantation 2017; 101:e280-e281. [PMID: 28471873 DOI: 10.1097/tp.0000000000001810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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35
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Marr KA. Infections in Hematopoietic Stem Cell Transplant Recipients. Infect Dis (Lond) 2017. [DOI: 10.1016/b978-0-7020-6285-8.00080-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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36
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First detection and complete genome sequence of a phylogenetically distinct human polyomavirus 6 highly prevalent in human bile samples. J Infect 2016; 74:50-59. [PMID: 27840269 DOI: 10.1016/j.jinf.2016.11.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 11/04/2016] [Accepted: 11/04/2016] [Indexed: 12/28/2022]
Abstract
Oncovirus-associated malignancies are potentially preventable diseases with major public health significance. Human polyomaviruses (HPyVs) may be associated with oncogenesis or symptomatic illnesses in immunocompromised patients, but the site of viral shedding of most recently discovered HPyVs remains obscure. Using real-time PCR assay using specific primers targeting the HPyV6 large tumor antigen gene, we detected a phylogenetically distinct HPyV6 which was highly prevalent in the bile samples of patients with malignant biliary obstruction (18.8%) and acute gallstone cholangitis (5.5%). The prevalence rate and mean viral load of this HPyV6 were highest in the cholangiocarcinoma subgroup (27.6% and 2.41 × 104copies/ml). These findings were confirmed with another real-time PCR assay using specific primers targeting the HPyV6 viral capsid protein 2 gene. These bile HPyV6 strains may represent a novel clade of HPyV6 as they formed a distinct cluster from the other HPyV6s and exhibited >2% differences in amino acid sequences in their major proteins. While HPyV6 was unlikely the cause of the patients' acute symptoms and liver dysfunction, the virus may be related to immunosuppression in patients with malignancy and/or important in the oncogenesis of cholangiocarcinoma in patients without coinfection with other oncogenic microbes. Further studies to ascertain a causative role of HPyV6 in cholangiocarcinoma should be conducted.
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37
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Vigil D, Konstantinov NK, Barry M, Harford AM, Servilla KS, Kim YH, Sun Y, Ganta K, Tzamaloukas AH. BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection. World J Transplant 2016; 6:472-504. [PMID: 27683628 PMCID: PMC5036119 DOI: 10.5500/wjt.v6.i3.472] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 08/25/2016] [Accepted: 09/08/2016] [Indexed: 02/05/2023] Open
Abstract
Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy (BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.
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38
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Philippe M, Ranchon F, Gilis L, Schwiertz V, Vantard N, Ader F, Labussiere-Wallet H, Thomas X, Nicolini FE, Wattel E, Ducastelle-Leprêtre S, Barraco F, Lebras L, Salles G, Michallet M, Rioufol C. Cidofovir in the Treatment of BK Virus–Associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2016; 22:723-730. [DOI: 10.1016/j.bbmt.2015.12.009] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Accepted: 12/15/2015] [Indexed: 12/16/2022]
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39
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Risk Factors Associated with Severity and Outcomes in Pediatric Patients with Hemorrhagic Cystitis. J Urol 2016; 195:1312-7. [PMID: 26926552 DOI: 10.1016/j.juro.2015.11.035] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/17/2015] [Indexed: 11/20/2022]
Abstract
PURPOSE Hemorrhagic cystitis is a complication of treatment of pediatric cancer with considerable variation in severity and morbidity. This study presents an analysis of hemorrhagic cystitis severity and treatment outcomes in a large pediatric population. MATERIALS AND METHODS Patients with hemorrhagic cystitis treated at St. Jude Children's Research Hospital® were identified from 1990 to 2010. Demographic data were gathered along with information pertaining to initial primary diagnosis, hemorrhagic cystitis diagnosis and treatment, and mortality. Statistical analyses were performed to evaluate associations between risk factors and severity of hemorrhagic cystitis as well as treatment outcomes. RESULTS Of the 285 patients who met inclusion criteria 54% were male. Mean age was 11.41 years. Mean time from initial primary diagnosis to hemorrhagic cystitis onset was 29 months. Noninvasive treatment was performed in 246 patients (86%) and operative intervention was required in 14 (4.9%). Bivariate analysis demonstrated that pelvic radiation therapy (p = 0.0002), any radiation therapy (p = 0.005), acute lymphocytic leukemia (p = 0.01), bone marrow transplantation (p = 0.0225), cyclophosphamide exposure (p = 0.0419) and BK virus positivity (p = 0.0472) were predictors of higher grade hemorrhagic cystitis. Factors correlating with the need for invasive management on bivariate analysis included pelvic radiation therapy (p = 0.0266), bone marrow transplantation (p = 0.0007), hematological malignancy (p = 0.0066), ifosfamide exposure (p = 0.0441) and male gender (p = 0.0383). Multivariate analysis showed independent effects of pelvic radiation therapy (p = 0.001) and delayed onset of hemorrhagic cystitis (p = 0.0444). CONCLUSIONS Severity of hemorrhagic cystitis and failure of noninvasive management correlate with several identifiable risk factors. Prospective identification of patients with these risk factors may allow for targeted early intervention in those at highest risk.
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40
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Peterson L, Ostermann H, Fiegl M, Tischer J, Jaeger G, Rieger CT. Reactivation of polyomavirus in the genitourinary tract is significantly associated with severe GvHD and oral mucositis following allogeneic stem cell transplantation. Infection 2016; 44:483-90. [PMID: 26792012 DOI: 10.1007/s15010-016-0872-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Accepted: 01/04/2016] [Indexed: 12/16/2022]
Abstract
PURPOSE BK-virus and JC-virus are the most common polyomaviridae associated with hemorrhagic cystitis in the allogeneic transplant setting. Hemorrhagic cystitis and symptomatic viruria caused by these viruses are a major cause of morbidity in patients undergoing allogeneic stem cell transplantation. METHODS We performed a retrospective evaluation on a highly uniform study population of 73 patients receiving allogeneic stem cell transplantation. Patients were treated according to the FLAMSA-RIC-protocol, and were examined for the incidence of BK-/JC-viruria and late-onset BK-positive hemorrhagic cystitis within a two-year period. RESULTS The occurrence of BK-viruria was correlated with published risk factors (acute GvHD, oral mucositis, donor type, conditioning, age, gender). Thirty patients (41 %) were found to excrete either BK-virus (n = 17), JC-virus (n = 3) or both (n = 10), of whom 18 patients (60 %) developed higher-grade hemorrhagic cystitis as opposed to none in the virus-negative control group. Higher grade GvHD (grade B-D) was more common in patients with viruria (p = 0.013) and also more common in patients with manifest hemorrhagic cystitis (p = 0.048). Similarly, oral mucositis was associated both with viruria (p = 0.014) and hemorrhagic cystitis (p = 0.005). Manifest cystitis but not viruria was significantly associated with male gender (p = 0.016). No significant correlation was found with age, conditioning with busulfane vs total body irradiation or related vs unrelated donor. CONCLUSIONS Severe GvHD and oral mucositis are significantly associated with reactivation of polyomaviridae in the genitourinary-tract already at the level of asymptomatic viruria.
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Affiliation(s)
- Lisa Peterson
- Department of Internal Medicine III, University of Munich, Munich, Germany
| | - Helmut Ostermann
- Department of Internal Medicine III, University of Munich, Munich, Germany
| | - Michael Fiegl
- Department of Internal Medicine III, University of Munich, Munich, Germany
| | - Johanna Tischer
- Department of Internal Medicine III, University of Munich, Munich, Germany
| | - Gundula Jaeger
- Max-von-Pettenkofer-Institut, University of Munich, Munich, Germany
| | - Christina T Rieger
- Department of Internal Medicine III, University of Munich, Munich, Germany. .,Internistische Lehrpraxis der LMU Germering, Ludwig-Maximilians-University Munich, Munich, Germany.
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41
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Hayden RT, Gu Z, Liu W, Lovins R, Kasow K, Woodard P, Srivastava K, Leung W. Risk factors for hemorrhagic cystitis in pediatric allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis 2015; 17:234-41. [PMID: 25648430 DOI: 10.1111/tid.12364] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Revised: 12/04/2014] [Accepted: 01/18/2015] [Indexed: 11/29/2022]
Abstract
BACKGROUND Hemorrhagic cystitis (HC) results in significant morbidity among hematopoietic stem cell transplant (HSCT) recipients. Several potential causes for HC have been postulated, including viral infection, but definitive evidence is lacking, particularly in pediatric HSCT patients. METHODS Ninety pediatric HSCT recipients were prospectively tested on a weekly basis for adenovirus (ADV) and BK virus (BKV) by quantitative real-time polymerase chain reaction in blood and urine samples. Results were correlated with the occurrence of grade II-IV HC. The odds ratio (OR) of HC (95% confidence interval) for BKV ≥1 × 10(9) copies/mL of urine was 7.39 (1.52, 35.99), with a P-value of 0.013. Those with acute graft-versus-host disease (aGVHD) also had higher odds of developing HC, with an OR of 5.34. Given a 20% prevalence rate of HC, positive and negative predictive values of 29% and 95% were seen with a cutoff of 10(9) copies/mL. RESULTS BK viremia did not reach significance as a risk factor for development of HC (P = 0.06). Only 8 patients showed ADV viruria and 7 showed ADV viremia; all had low viral loads and 4 had no evidence of HC. CONCLUSION HC in pediatric HSCT is correlated most strongly to elevated urinary viral load of BKV and to aGVHD, but less strongly to BK viremia.
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Affiliation(s)
- R T Hayden
- Pathology Department, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
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42
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Correlation of the clinical parameters with sonographic findings of hemorrhagic cystitis in pediatric hematooncology patients. SPRINGERPLUS 2015; 4:577. [PMID: 26543712 PMCID: PMC4628028 DOI: 10.1186/s40064-015-1380-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 09/27/2015] [Indexed: 11/10/2022]
Abstract
To find a relationship between clinical and sonographic appearance of hemorrhagic cystitis (HC) in pediatric hematooncology patients. Clinical and sonographic findings of 31 children (M:F = 18:13; mean age, 12.7 years) with HC in pediatric hematooncology patients were reviewed. For each patient, the onset of HC after transplantation, use of bladder-toxic agent, presence of BK viruria, and duration of disease were reviewed. Sonographic findings including bladder wall thickness (BWT), the type of bladder wall thickening (nodular vs. diffuse), occurrence of hydronephrosis or pyelonephritis were reviewed. We analyzed sonographic appearance and clinical manifestations of HC. HC occurred within 4 months after HSCT/BMT. 27 patients (87.0 %) were positive for BK viruria and 24 patients (77.4 %) took bladder-toxic agents. On sonography, nodular type bladder wall thickening was more frequent (54.8 %), and BWT was thicker in this group (p = 0.003). There was a positive correlation between the BWT on initial sonography and duration of cystitis (r2 = 0.340). Hydronephrosis developed in 25.8 % of patients with HC, and as HC persisted longer, hydronephrosis occurred more (p = 0.004). In patients with HC after HSCT/BMT, the BWT on initial sonography correlates well with the duration of cystitis. And, longer time of HC develops the risk of hydronephrosis.
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43
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Moro JC, Junior ESB, Riccetto CLZ, Palma P. Fulminating Hemorrhagic Cystitis: New Trends from Etiology to Treatment. CURRENT BLADDER DYSFUNCTION REPORTS 2015. [DOI: 10.1007/s11884-015-0305-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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44
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Cesaro S, Tridello G, Pillon M, Calore E, Abate D, Tumino M, Carucci N, Varotto S, Cannata E, Pegoraro A, Barzon L, Palù G, Messina C. A Prospective Study on the Predictive Value of Plasma BK Virus-DNA Load for Hemorrhagic Cystitis in Pediatric Patients After Stem Cell Transplantation. J Pediatric Infect Dis Soc 2015; 4:134-42. [PMID: 26407413 DOI: 10.1093/jpids/piu043] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2013] [Accepted: 03/11/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND In hematopoietic stem cell transplantation (HSCT), late hemorrhagic cystitis (HC) has been associated with BK virus (BKV) infection. We assessed the value of plasma BKV load in predicting HC. METHODS Plasma and urine BKV-DNA load were assessed prospectively in 107 pediatric patients. RESULTS Twenty patients developed grade II and III HC, with 100-day cumulative incidence of 18.8%. At diagnosis of HC, the median load of BKV DNA was 2.3 × 10(3) copies/mL. A plasma BKV-DNA load of 10(3) copies/mL had a sensitivity of 100% and a specificity of 86% with a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 39% for HC. A urine BKV-DNA load of >10(7) copies/mL had a sensitivity of 86% and a specificity of 60% with a NPV of 98% and a PPV of 14% for HC. A BKV load of 10(3) copies/mL on plasma was significantly associated with HC in multivariate analysis (hazard ratio [HR], 6.1; P = .0006). Patients with HC had a significantly higher risk of mortality than patients who did not have HC (HR, 2.6; P = .018). CONCLUSIONS The above values were used to monitor plasma BKV-DNA load, and they provided a better prediction of patients at risk of HC than urine BKV-DNA load.
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Affiliation(s)
- Simone Cesaro
- Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy Pediatric Hematology Oncology, Department of Pediatrics
| | - Gloria Tridello
- Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy Pediatric Hematology Oncology, Department of Pediatrics
| | - Marta Pillon
- Pediatric Hematology Oncology, Department of Pediatrics
| | | | - Davide Abate
- Department of Molecular Medicine, University of Padova, Italy
| | | | | | | | - Elisa Cannata
- Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | - Anna Pegoraro
- Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | - Luisa Barzon
- Department of Molecular Medicine, University of Padova, Italy
| | - Giorgio Palù
- Department of Molecular Medicine, University of Padova, Italy
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Brincidofovir (CMX001) inhibits BK polyomavirus replication in primary human urothelial cells. Antimicrob Agents Chemother 2015; 59:3306-16. [PMID: 25801568 DOI: 10.1128/aac.00238-15] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Accepted: 03/17/2015] [Indexed: 02/08/2023] Open
Abstract
BK polyomavirus (BKPyV)-associated hemorrhagic cystitis (PyVHC) complicates 5 to 15% of allogeneic hematopoietic stem cell transplantations. Targeted antivirals are still unavailable. Brincidofovir (BCV; previously CMX001) has shown inhibitory activity against diverse viruses, including BKPyV in a primary human renal tubule cell culture model of polyomavirus-associated nephropathy. We investigated the effects of BCV in BKPyV-infected and uninfected primary human urothelial cells (HUCs), the target cells of BKPyV in PyVHC. The BCV concentrations causing 50 and 90% reductions (EC50 and EC90) in the number of intracellular BKPyV genome equivalents per cell (icBKPyV) were 0.27 μM and 0.59 μM, respectively. At 0.63 μM, BCV reduced viral late gene expression by 90% and halted progeny release. Preinfection treatment for only 24 h reduced icBKPyV similarly to treatment from 2 to 72 h postinfection, while combined pre- and postinfection treatment suppressed icBKPyV completely. After investigating BCV's effects on HUC viability, mean selectivity indices at 50 and 90% inhibition (SI50 and SI90) calculated for cellular DNA replication were 2.7 and 2.9, respectively, those for mitochondrial activity were 8.9 and 10.4, those for total ATP were 8.6 and 8.2, and those for membrane integrity were 25.9 and 16.7. The antiviral and cytostatic effects, but less so the cytotoxic effects, were inversely related to cell density. The cytotoxic effects at concentrations of ≥10 μM were rapid and likely related to BCV's lipid moiety. After carefully defining the antiviral, cytostatic, and cytotoxic properties of BCV in HUCs, we conclude that a preemptive or prophylactic approach in PyVHC is likely to give the best results.
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46
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Han SB, Cho B, Kang JH. BK virus-associated hemorrhagic cystitis after pediatric stem cell transplantation. KOREAN JOURNAL OF PEDIATRICS 2014; 57:514-9. [PMID: 25653684 PMCID: PMC4316594 DOI: 10.3345/kjp.2014.57.12.514] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Accepted: 10/08/2014] [Indexed: 02/08/2023]
Abstract
Hemorrhagic cystitis is a common stem cell transplantation-related complication. The incidence of early-onset hemorrhagic cystitis, which is related to the pretransplant conditioning regimen, has decreased with the concomitant use of mesna and hyperhydration. However, late-onset hemorrhagic cystitis, which is usually caused by the BK virus, continues to develop. Although the BK virus is the most common pathogenic microorganism of poststem cell transplantation late-onset hemorrhagic cystitis, pediatricians outside the hemato-oncology and nephrology specialties tend to be unfamiliar with hemorrhagic cystitis and the BK virus. Moreover, no standard guidelines for the early diagnosis and treatment of BK virus-associated hemorrhagic cystitis after stem cell transplantation have been established. Here, we briefly introduce poststem cell transplantation BK virus-associated hemorrhagic cystitis.
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Affiliation(s)
- Seung Beom Han
- Department of Pediatrics, The Catholic University of Korea College of Medicine, Seoul, Korea. ; The Vaccine Bio Research Institute, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Bin Cho
- Department of Pediatrics, The Catholic University of Korea College of Medicine, Seoul, Korea. ; The Catholic Blood and Marrow Transplantation Center, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jin Han Kang
- Department of Pediatrics, The Catholic University of Korea College of Medicine, Seoul, Korea. ; The Vaccine Bio Research Institute, The Catholic University of Korea College of Medicine, Seoul, Korea
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47
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Satyanarayana G, Hammond SP, Broge TA, Mackenzie MR, Viscidi R, Politikos I, Koralnik IJ, Cutler CS, Ballen K, Boussiotis V, Marty FM, Tan CS. BK polyomavirus reactivation after reduced-intensity double umbilical cord blood cell transplantation. Transpl Immunol 2014; 32:116-20. [PMID: 25536223 DOI: 10.1016/j.trim.2014.12.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Revised: 12/11/2014] [Accepted: 12/11/2014] [Indexed: 12/28/2022]
Abstract
Serial serum samples from 27 patients who underwent double umbilical cord blood transplantation (dUCBT) were analyzed for BK polyomavirus (BKPyV) DNA by real-time PCR and BKPyV-specific immune globulin by ELISA. Clinical data were collected on all patients. All pre-transplant sera had detectable anti-BKPyV IgG. Fifteen patients (56%) had detectable serum BKPyV DNA (median 8.9 × 10(4) copies/ml; range 4.1 × 10(3)-7.9 × 10(6) copies/ml) a median of 40 days (range, 27-733 days) after dUCBT, with highest viral loads on Day 100 assessment. The cumulative probability of developing BKPyV viremia by Day 100 was 0.52 (95% CI, 0.33-0.71). Six of 15 patients with BKPyV viremia experienced hemorrhagic cystitis by Day 100. By Day 100, there was a trend towards higher BKPyV viral loads in sera of patients with hemorrhagic cystitis than in those BKPyV viremic patients without hemorrhagic cystitis (p = 0.06). BKPyV viremia was associated with significantly higher anti-BKPyV IgM values at 6 months post-dUCBT (P = 0.003). BKPyV viremia occurs early after dUBCT and is associated with a detectable humoral immune response by 6 months post-dUBCT.
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Affiliation(s)
- Gowri Satyanarayana
- Division of Infectious Disease, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA; Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Sarah P Hammond
- Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Thomas A Broge
- Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Neurovirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Matthew R Mackenzie
- Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Neurovirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Raphael Viscidi
- Division of Developmental Neurovirology, Johns Hopkins University Medical Center, Baltimore, MD, USA
| | - Ioannis Politikos
- Division of Neurovirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Igor J Koralnik
- Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Neurovirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Corey S Cutler
- Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Karen Ballen
- Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Vassiliki Boussiotis
- Division of Neurovirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Francisco M Marty
- Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Chen Sabrina Tan
- Division of Infectious Disease, Beth Israel Deaconess Medical Center, Boston, MA, USA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Neurovirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
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48
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Wang Y, Chen F, Gu B, Chen G, Chang H, Wu D. Mesenchymal stromal cells as an adjuvant treatment for severe late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Acta Haematol 2014; 133:72-7. [PMID: 25139500 DOI: 10.1159/000362530] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Accepted: 03/30/2014] [Indexed: 12/14/2022]
Abstract
The management of severe late-onset hemorrhagic cystitis (LO-HC) after allogeneic hematopoietic stem cell transplantation (HSCT) is still challenging. Because mesenchymal stromal cells (MSCs) possess anti-inflammatory and tissue repair-promoting properties, we retrospectively analyzed the efficacy and safety of MSC infusions in 7 of 33 patients with severe LO-HC after allogeneic HSCT. During treatment, each patient received at least one MSC infusion of Wharton's jelly derived from the umbilical cord of a third-party donor. In 6 patients, MSC treatment was initiated within 3 days of gross hematuria onset, while the 7th patient received an infusion 40 days later. The median dose was 1.0 (0.8-1.6) × 10(6)/kg. Five of 7 patients responded to treatment. Notably, gross hematuria promptly disappeared in 3 patients after 1 infusion, with a time to remission not seen in patients without MSC infusion. Two patients showed no response even after several infusions. No acute or late complications were recorded. Our findings indicate that MSC transfusion might be a feasible and safe supplemental therapy for patients with severe LO-HC after allogeneic HSCT.
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Affiliation(s)
- Ying Wang
- Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, PR China
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49
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The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD. Bone Marrow Transplant 2014; 49:1528-34. [PMID: 25111517 DOI: 10.1038/bmt.2014.181] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2014] [Revised: 06/16/2014] [Accepted: 06/18/2014] [Indexed: 01/13/2023]
Abstract
Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic SCT (allo-HSCT). Several risk factors have been suggested including BU-containing myeloablative conditioning, unrelated donors and GVHD, but these have not been consistently reported. We conducted a retrospective study including 339 allo-HSCT recipients between 2009 and 2012. Of 339 patients, 79 (23.3%) developed HC with 2-year cumulative incidence of 24.0% (95% confidence interval, 19.4-28.9). The median onset time was 45 days (range, 16-430) after allo-HSCT. Sixty-two patients (84%) out of 74 evaluated for urine BK virus PCR testing showed a positive result (mean 2.0 × 10(10) copies of DNA per mL). In univariate analysis, myeloablative conditioning, HLA-mismatched donor, CMV viremia and acute GVHD (aGVHD) grade 3-4 were significantly associated with the risk of HC. Multivariate analysis confirmed all associating factors identified in univariate analysis except for HLA-mismatched donor: myeloablative conditioning (hazard ratio (HR) 2.63, P=0.003), CMV viremia (HR 1.88, P=0.014) and aGVHD grade 3-4 (HR 1.71, P=0.029). HC did not affect OS or non-relapse mortality. Symptomatic HC is a frequent complication following allo-HSCT, with a 2-year cumulative incidence of 24.0%. Three clinical factors associated with HC were identified including myeloablative conditioning, CMV viremia and severe aGVHD.
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50
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Van der Aa F, Beckley I, de Ridder D. Polyomavirus BK--a potential new therapeutic target for painful bladder syndrome/interstitial cystitis? Med Hypotheses 2014; 83:317-20. [PMID: 24973060 DOI: 10.1016/j.mehy.2014.06.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2014] [Revised: 06/04/2014] [Accepted: 06/06/2014] [Indexed: 01/08/2023]
Abstract
AIMS To investigate the role of urinary BK polyoma virus (BKPyV) in the pathophysiology and prognosis of patients with painful bladder syndrome/interstitial cystitis (PBS/IC). METHODS Urine samples were collected from 15 patients with PBS/IC and 8 control patients (with urolithiasis, overactive bladder and benign prostatic hyperplasia). BKPyV titres were quantitatively determined using real time PCR. Fisher's exact test was used to compare virus titre levels between the two groups. The PBS/IC patients subsequently underwent cystoscopy, hydrodistension and bladder biopsy. Finally, a chart review was performed in order to correlate PBS/IC subtype and treatment outcomes with BKPyV status. RESULTS Positive BKPyV titres were found in 11 out of 15 PBS/IC patients but none of the controls. Cystoscopy was performed in 13 of the 15 PBS/IC patients (in 2 BKPyV positive patients, cystoscopy was not performed). Bladder ulceration and glomerulations were observed in all 9 BKPyV positive PBS/IC patients but only 1 out of 4 BKPyV negative patients. None of the non-ulcerative PBS/IC patients had BKPyV positive urine. Viral titres were not predictive of the clinical course however, 3 patients with the highest viral titres eventually underwent cystectomy. CONCLUSIONS We identified BKPyV in the urine of virtually all our patients with ulcerative PBS/IC. This finding suggests there may be a pathophysiological association between the virus and the haemorrhagic manifestations of PBS/IC. Classifying PBS/IC patients into BKPyV positive or negative groups may prove useful in future research on markers of disease prognosis and the subtypes of PBS/IC. We believe that BKPyV may therefore have a role as a potential therapeutic target in PBS/IC.
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Affiliation(s)
- Frank Van der Aa
- Department of Urology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
| | - Ian Beckley
- Department of Urology, Pinderfields General Hospital, Aberford Road, Wakefield WF1 4DG, United Kingdom.
| | - Dirk de Ridder
- Department of Urology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
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