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Wei A, Jing Y, Zhu G, Wang B, Yang J, Jia C, Luo Y, Yan Y, Zheng J, Zhou X, Qin M, Wang T. Analysis of BK Virus Infection in Children After Hematopoietic Cell Transplantation: A Retrospective Single-center Study. J Pediatr Hematol Oncol 2024; 46:e487-e492. [PMID: 39008534 DOI: 10.1097/mph.0000000000002922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Accepted: 06/24/2024] [Indexed: 07/17/2024]
Abstract
BACKGROUND BK virus (BKV) is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT). Viruses can be found in urine and serum of immunocompromised patients. OBJECTIVE This study aimed to evaluate the incidence, clinical course, and risk factors for BKV infection in children undergoing HSCT. METHODS Retrospectively analyzed children who underwent HSCT at Beijing Children's Hospital, Capital Medical University from June 2020 to June 2022. Data related to the clinical manifestations, engraftment, and prognosis were extracted from medical records. Patients were divided into the case group and the control group, according to the BKV infection or not after HSCT. RESULTS A total of 149 patients were enrolled in this study, and 61 (40.9%) patients developed BKV infection after HSCT. Among the 61 patients, BKV load was detected in all patients in urine samples and 22 patients in blood samples. The median value of BKV DNA copies in urine and plasma were 9.50×10 7 (5.37×10 2 to 6.84×10 9 ) copies/mL and 2.97×10 3 (9.96×10 2 to 3.58×10 8 ) copies/mL, respectively. The median time from beginning of the conditioning regimen to BKV infection was 23 (0 to 273) days, and the first positive time of urinary BKV was earlier than that of blood (13.5 d [0.0 to 123.0 d] vs. 30.5 d [7.0 to 165.0 d], P =0.003). Among the patients with BKV infection, 36 (59.0%) patients met the diagnosis of hemorrhagic cystitis (HC), and the incidence was higher than that in the control group ( P <0.001). Similarly, 15 (24.6%) patients developed renal function damage in the case group and the proportion was higher than that in the control group. The median follow-up was 5.67 (0.03 to 24.90) months, and there was no significant difference in 1-year overall survival rate between the case group and the control group (84.2%±5.7% vs. 95.3%±2.3%, P =0.688), but the incidence of TA-TMA/VOD (31.1%) and diffuse alveolar hemorrhage (9.8%) in the case group was higher than that in the control group ( P =0.002 and 0.038, respectively). Multivariate analysis showed that age above 5 years old (OR=9.039, 95% CI: 3.561-24.333, P <0.001) and use of MMF (OR=2.708, 95% CI: 1.041-7.044, P <0.05) were independent risk factors for BKV infection after HSCT. CONCLUSION Among children after HSCT, the incidence of BKV infection was high and BKV infection was associated with an increased incidence of TA-TMA/VOD and diffuse alveolar hemorrhage. Patients older than 5 years of age at the time of HSCT and treated with MMF were more likely to develop BKV infection.
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Affiliation(s)
- Ang Wei
- Beijing Key Laboratory of Pediatric Hematology Oncology
- National Key Discipline of Pediatrics
- Department of Stem cell Transplantation, Beijing Children's Hospital, Capital Medical University
- Key Laboratory of Major Diseases in Children, Ministry of Education
- National Center for Children's Health, Beijing, China
| | - Yuanfang Jing
- Beijing Key Laboratory of Pediatric Hematology Oncology
- National Key Discipline of Pediatrics
- Department of Stem cell Transplantation, Beijing Children's Hospital, Capital Medical University
- Key Laboratory of Major Diseases in Children, Ministry of Education
- National Center for Children's Health, Beijing, China
| | - Guanghua Zhu
- Beijing Key Laboratory of Pediatric Hematology Oncology
- National Key Discipline of Pediatrics
- Department of Stem cell Transplantation, Beijing Children's Hospital, Capital Medical University
- Key Laboratory of Major Diseases in Children, Ministry of Education
- National Center for Children's Health, Beijing, China
| | - Bin Wang
- Beijing Key Laboratory of Pediatric Hematology Oncology
- National Key Discipline of Pediatrics
- Department of Stem cell Transplantation, Beijing Children's Hospital, Capital Medical University
- Key Laboratory of Major Diseases in Children, Ministry of Education
- National Center for Children's Health, Beijing, China
| | - Jun Yang
- Beijing Key Laboratory of Pediatric Hematology Oncology
- National Key Discipline of Pediatrics
- Department of Stem cell Transplantation, Beijing Children's Hospital, Capital Medical University
- Key Laboratory of Major Diseases in Children, Ministry of Education
- National Center for Children's Health, Beijing, China
| | - Chenguang Jia
- Beijing Key Laboratory of Pediatric Hematology Oncology
- National Key Discipline of Pediatrics
- Department of Stem cell Transplantation, Beijing Children's Hospital, Capital Medical University
- Key Laboratory of Major Diseases in Children, Ministry of Education
- National Center for Children's Health, Beijing, China
| | - Yanhui Luo
- Beijing Key Laboratory of Pediatric Hematology Oncology
- National Key Discipline of Pediatrics
- Department of Stem cell Transplantation, Beijing Children's Hospital, Capital Medical University
- Key Laboratory of Major Diseases in Children, Ministry of Education
- National Center for Children's Health, Beijing, China
| | - Yan Yan
- Beijing Key Laboratory of Pediatric Hematology Oncology
- National Key Discipline of Pediatrics
- Department of Stem cell Transplantation, Beijing Children's Hospital, Capital Medical University
- Key Laboratory of Major Diseases in Children, Ministry of Education
- National Center for Children's Health, Beijing, China
| | - Jie Zheng
- Beijing Key Laboratory of Pediatric Hematology Oncology
- National Key Discipline of Pediatrics
- Department of Stem cell Transplantation, Beijing Children's Hospital, Capital Medical University
- Key Laboratory of Major Diseases in Children, Ministry of Education
- National Center for Children's Health, Beijing, China
| | - Xuan Zhou
- Beijing Key Laboratory of Pediatric Hematology Oncology
- National Key Discipline of Pediatrics
- Department of Stem cell Transplantation, Beijing Children's Hospital, Capital Medical University
- Key Laboratory of Major Diseases in Children, Ministry of Education
- National Center for Children's Health, Beijing, China
| | - Maoquan Qin
- Beijing Key Laboratory of Pediatric Hematology Oncology
- National Key Discipline of Pediatrics
- Department of Stem cell Transplantation, Beijing Children's Hospital, Capital Medical University
- Key Laboratory of Major Diseases in Children, Ministry of Education
- National Center for Children's Health, Beijing, China
| | - Tianyou Wang
- Beijing Key Laboratory of Pediatric Hematology Oncology
- National Key Discipline of Pediatrics
- Department of Stem cell Transplantation, Beijing Children's Hospital, Capital Medical University
- Key Laboratory of Major Diseases in Children, Ministry of Education
- National Center for Children's Health, Beijing, China
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da Silva Selistre L, Renard C, Bacchetta J, Goutagny MP, Hu J, Carla de Souza V, Bertrand Y, Dubourg L, Domenech C. Teenagers and young adults with a past of allogenic hematopoietic stem cell transplantation are at significant risk of chronic kidney disease. Pediatr Nephrol 2022; 37:1365-1375. [PMID: 34735600 DOI: 10.1007/s00467-021-05319-x] [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: 07/15/2021] [Revised: 09/21/2021] [Accepted: 09/27/2021] [Indexed: 11/25/2022]
Abstract
BACKGROUND Allogenic hematopoietic stem cell transplantation (aHSCT) remains the treatment of choice for some malignant hemopathies in children, albeit with the risk of long-term consequences, including chronic kidney disease (CKD). METHODS In our single tertiary referral center, we retrospectively assessed the long-term renal outcome in a cohort of children and adolescents who had undergone aHSCT for malignant hemopathies between 2003 and 2017. We distinguished glomerular and tubular dysfunctions and assessed the accuracy of the most common formula(s) to estimate glomerular filtration rate (GFR) during standard clinical follow-up. RESULTS Among the 166 patients who had received aHSCT, 61 underwent kidney functional assessment 1 to 10 years post-transplantation. Twenty-seven patients (44.3%) had a CKD with glomerular impairment, including 20 patients with a GFR < 90 mL/min/1.73 m2, and among these, 5 patients < 60 mL/min/1.73 m2. Patients with tubular signs had a significantly higher baseline GFR: 112 mL/min/1.73 m2 [100; 120] versus 102 [99.0; 112.5] for patients without kidney involvement, and 76 [61; 86] for patients with CKD (p < 0.01). Schwartz, CKiDU25, and EKFC formulas significantly overestimated mGFR, with a P30% ≤ 30%, which could lead to overlooking CKD diagnosis in this population. No patient reached kidney failure. CONCLUSIONS In conclusion, our study shows that CKD represents an important long-term sequela for children and adolescents who undergo aHSCT for malignant hemopathies, either with glomerular dysfunction or with the more insidious tubular dysfunction which could potentially impact growth. These patients could benefit from specialized long-term nephrology follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Luciano da Silva Selistre
- Néphrologie, Dialyse, Hypertension et Exploration Fonctionnelle Rénale, Groupement Hospitalier Edouard-Herriot, Hospices Civils de Lyon, Lyon, France
- Universidade de Caxias Do Sul, Programa de Pós Graduação Em Ciências da Saúde, Caxias do Sul, Brazil
- Hospital Geral de Caxias Do Sul, Caxias do Sul, Brazil
| | - Cécile Renard
- Institut d'Hématologie et d'Oncologie Pédiatrique, Hospices Civils de Lyon, Université Lyon 1, 1 place Professeur Joseph Renault, 69008, Lyon, France
| | - Justine Bacchetta
- Centre de Référence Des Maladies Rénales Rares, Service de Néphrologie, Rhumatologie et Dermatologie Pédiatriques, Hospices Civils de Lyon, Université Lyon 1, Lyon, France
- Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, France
| | - Marie-Pierre Goutagny
- Institut d'Hématologie et d'Oncologie Pédiatrique, Hospices Civils de Lyon, Université Lyon 1, 1 place Professeur Joseph Renault, 69008, Lyon, France
| | - Julie Hu
- Institut d'Hématologie et d'Oncologie Pédiatrique, Hospices Civils de Lyon, Université Lyon 1, 1 place Professeur Joseph Renault, 69008, Lyon, France
| | - Vandréa Carla de Souza
- Universidade de Caxias Do Sul, Programa de Pós Graduação Em Ciências da Saúde, Caxias do Sul, Brazil
- Hospital Geral de Caxias Do Sul, Caxias do Sul, Brazil
| | - Yves Bertrand
- Institut d'Hématologie et d'Oncologie Pédiatrique, Hospices Civils de Lyon, Université Lyon 1, 1 place Professeur Joseph Renault, 69008, Lyon, France
- Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, France
| | - Laurence Dubourg
- Néphrologie, Dialyse, Hypertension et Exploration Fonctionnelle Rénale, Groupement Hospitalier Edouard-Herriot, Hospices Civils de Lyon, Lyon, France
- Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, France
| | - Carine Domenech
- Institut d'Hématologie et d'Oncologie Pédiatrique, Hospices Civils de Lyon, Université Lyon 1, 1 place Professeur Joseph Renault, 69008, Lyon, France.
- Faculté de Médecine Et de Maïeutique Lyon Sud, Université Claude Bernard Lyon 1, Lyon, France.
- Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052, CNRS 5286, Université Lyon 1, Lyon, France.
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Yozgat A, Bozkaya I, Aksu T, Isik P, Kanbur M, Tiryaki T, Yarali N, Özbek N. Analysis of hemorrhagic cystitis and BK viremia in children after hematopoietic stem cell transplantation. INDIAN JOURNAL OF TRANSPLANTATION 2022. [DOI: 10.4103/ijot.ijot_84_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Bezruk VV, Bezruk TO, Godovanets OS, Sheremet MI, Yurniuk SV, Velia MI, Makarova OV, Yurkiv OI, Maksymiv OO. Peculiarities of the regional dynamics of the prevalence and incidence of cystitis in children. J Med Life 2021; 14:210-215. [PMID: 34104244 PMCID: PMC8169140 DOI: 10.25122/jml-2020-0121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
In a child, cystitis (non-specific microbial inflammation of the mucous membrane of the bladder) is considered to be a dangerous disease; the prolongation of the process is usually associated with a delayed diagnosis. The aim of this work was to analyze the health status of the child population of the Chernivtsi region, especially the dynamics of the prevalence and incidence of cystitis. The official statistical data have been studied (reports on the state of medical care for children in the Chernivtsi region and data from the Center of Medical Statistics of the Ministry of Healthcare from 2006 to 2017); information-analytical and statistical methods have been used for the purpose of this study. Attention should be drawn to the significantly high prevalence of cystitis among children aged 15–17 years, especially in the Chernivtsi region as during period I (8.7±0.6 vs. 4.3±0.3 in Ukraine) and II (11.7±1.0 and 5.7±0.4, respectively, per 1000 people). Moreover, over the years, the growth of indicators acquires intensity, while this process is more than twice as pronounced in Chernivtsi. Thus, the growth rate was 65.0% in 2006–2011 and 90.3% in 2012–2017 vs. 27.2% and 32.8% in Ukraine, respectively. The identified data indicate the need to provide specialized care to children with infectious and inflammatory diseases of the urinary system of the Chernivtsi region and the need to improve regional clinical routes of patients with infectious and inflammatory diseases of the urinary system.
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Affiliation(s)
| | - Tetyana Oleksandrivna Bezruk
- Department of Internal Medicine and Infectious Diseases, Bukovinian State Medical University, Chernivtsi, Ukraine
| | - Oleksii Serhiiovych Godovanets
- Department of Pediatrics, Neonatology and Perinatology Medicine, Bukovinian State Medical University, Chernivtsi, Ukraine
| | | | | | | | - Olena Viktorivna Makarova
- Department of Care for Patients and Higher Nursing Education, Bukovinian State Medical University, Chernivtsi, Ukraine
| | - Oksana Ivanivna Yurkiv
- Department of Care for Patients and Higher Nursing Education, Bukovinian State Medical University, Chernivtsi, Ukraine
| | - Oleh Olehovych Maksymiv
- Department of Orthopedic Dentistry, Bukovinian State Medical University, Chernivtsi, Ukraine
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Ruderfer D, Wu M, Wang T, Srivaths PR, Krance RA, Naik S, Bocchini CE. BK Virus Epidemiology, Risk Factors, and Clinical Outcomes: An Analysis of Hematopoietic Stem Cell Transplant Patients at Texas Children's Hospital. J Pediatric Infect Dis Soc 2021; 10:492-501. [PMID: 33416086 DOI: 10.1093/jpids/piaa147] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 11/11/2020] [Indexed: 11/13/2022]
Abstract
BACKGROUND BK virus-associated hemorrhagic cystitis (BKV-HC) is a serious complication after hematopoietic stem cell transplantation (HSCT). METHODS A retrospective review was performed to determine the frequency of BKV-HC and identify risk factors and renal morbidity associated with BKV-HC in pediatric HSCT recipients at our institution. RESULTS A total of 314 pediatric recipients underwent allogeneic HSCT for either malignant (173, 55.1%) or nonmalignant disorders (141, 44.9%) from January 1, 2011, to December 31, 2015, with a minimum follow-up of 5 years post-HSCT. Severe BKV-HC (grades 3 and 4) was prevalent in 46 out of 67 (68.7%) recipients. Timing to presentation of severe BKV-HC (grades 3 and 4) occurred at a median of 37 days (26, 74; IQ1, IQ3) post-HSCT, with the duration of macroscopic hematuria lasting a median of 37.5 days (18, 71; IQ1, IQ3). In the first 60 days post-HSCT, peak acute kidney injury (AKI) stages 2 and 3 were seen more frequently in HSCT recipients who developed BKV-HC than those without (P = .004). Similarly, during post-HSCT days 61 to 100, peak AKI stage 3 was also more frequently seen in HSCT recipients who already developed BKV-HC prior to or during this time period than those without BKV-HC (P = .0002). Recipients who developed BKV-HC within 1 year of HSCT had more frequent mild to moderate chronic kidney disease (CKD stages 2-3) than those without BKV-HC (P = .002 and .007, respectively). On multivariate analysis, BKV-HC was associated with all-cause mortality (hazard ratio [HR]: 2.22; 95% confidence interval [CI]: 1.35-3.65). The following clinical variables were associated with time to development of HC on multivariate analysis: age (subdistribution HR [sHR] 1.11; 95% CI: 1.06-1.16) and myeloabalative conditioning regimen (sHR 4.2; 95% CI: 2.12-8.34). CONCLUSIONS Pediatric HSCT patients with BKV-HC experience significant morbidity and mortality. Renal morbidity, including AKI and CKD, is associated with BKV-HC.
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Affiliation(s)
- Daniel Ruderfer
- Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA
| | - Mengfen Wu
- Biostatistics Shared Resource, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA
| | - Tao Wang
- Biostatistics Shared Resource, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA
| | - Poyyapakkam R Srivaths
- Department of Pediatrics, Section of Nephrology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA
| | - Robert A Krance
- Department of Pediatrics, Section of Hematology and Oncology, Bone Marrow/Stem Cell Transplant Program, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA
| | - Swati Naik
- Department of Pediatrics, Section of Hematology and Oncology, Bone Marrow/Stem Cell Transplant Program, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA
| | - Claire E Bocchini
- Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA
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KAYA NN, BAYRAM İ, ÖZTÜRK G, SEZGİN G, KÜPELİ S, YARKIN F. BK Virus Infections in Pediatric Patients with Hematopoietic Stem Cell Transplantation. DÜZCE TIP FAKÜLTESI DERGISI 2020; 22:180-184. [DOI: 10.18678/dtfd.781232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Aim: BK virus (BKV)-associated hemorrhagic cystitis (HC) is a common complication in patients after hematopoietic stem cell transplantation (HSCT). The aim of this study was to investigate the incidence of BKV infection in pediatric patients receiving HSCT.
Material and Methods: Total of 51 patients aged between 16 months and 16 years old and followed up between October 2015 and September 2017 were included in the study. The patients were monitored by quantitative real-time polymerase chain reaction (Anatolia Geneworks, Turkey) test for the detection of BKV DNA in urine and blood.
Results: Of patients, 46 received allogeneic HSCT and 5 autologous HSCT. BKV DNA positivity was detected in urine and/or blood of total 27 (52.9%) patients in whom 26 (56.5%) of 46 patients with allogeneic transplantation, and 1 (20.0%) of 5 patients with autologous transplantation. BKV viral load in urine >107 copies/ml required for preemptive treatment was detected in 12 (26.1%) of 46 patients received allogeneic HSCT. The development of HC was prevented in 9 (75.0%) of the 12 patients given preemptive treatment, while 3 (25.0%) cases developed HC and cured by treatment. BKV viruria was detected >109 copies/ml in two weeks before the onset of HC and was accepted as a prognostic indicator for predictive diagnosis of HC. BKV viremia was found >104 copies/ml in 1 patient within two weeks before the onset of cystitis.
Conclusion: Screening for BKV infection, especially BKV viruria in HSCT patients, is recommended for the predictive diagnosis of HC in patients at high risk.
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Low incidence of hemorrhagic cystitis following ex vivo T-cell depleted haploidentical hematopoietic cell transplantation in children. Bone Marrow Transplant 2019; 55:207-214. [PMID: 31527820 DOI: 10.1038/s41409-019-0672-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Revised: 05/29/2019] [Accepted: 06/30/2019] [Indexed: 11/09/2022]
Abstract
Hemorrhagic cystitis (HC) is a debilitating complication following allogenic hematopoietic cell transplantation (HCT). HLA disparity and T-cell depletion have been implicated as risk factors for HC. However, reports on the incidence and risk factors for HC in ex vivo T-cell depleted haploidentical HCT (haploHCT) in children are lacking. We studied 96 haploHCT procedures performed in 83 children between 2002 and 2017. Sixty-three patients were diagnosed with a malignant disease and 20 with nonmalignant disease. All but three patients with SCID underwent myelotoxic and/or lymphotoxic conditioning therapy. Grafts were CD3+ (36.5%) or TcRαβ+ (63.5%) depleted to prevent graft versus host disease (GvHD). Fourteen patients (14.6%) were diagnosed with HC; 12 (12.5%) had clinically significant stage II-IV HC. All patients with HC had BK viruria and/or viremia. Increasing age and chemotherapeutic treatment prior to conditioning were identified as risk factors for HC. Immune recovery did not significantly differ between patients with and without HC. Thus, we report a low incidence of HC in pediatric haploHCT using ex vivo T-cell depletion. The combination of a reduced toxicity conditioning regimen, and typically absent pharmaceutical post-HCT GvHD prophylaxis in our patients might have contributed to the decreased the risk of HC, despite HLA disparity.
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Obeid KM. Infections with DNA Viruses, Adenovirus, Polyomaviruses, and Parvovirus B19 in Hematopoietic Stem Cell Transplant Recipients and Patients with Hematologic Malignancies. Infect Dis Clin North Am 2019; 33:501-521. [PMID: 30940465 DOI: 10.1016/j.idc.2019.02.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Infections due to adenovirus, polyomaviruses (BK and JC viruses), and parvovirus B19 may not be as common as infections due to other DNA viruses, such as cytomegalovirus in patients with hematological malignancies and the recipients of hematopoietic stem cell transplantation. However, these infections may result in life-threatening diseases that significantly impact patients' recovery, morbidity, and mortality. Treating physicians should be aware of the diseases associated with these viruses, the patient populations at increased risk for complications due to these infections, and the available diagnostic and therapeutic approaches.
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Affiliation(s)
- Karam M Obeid
- Division of Infectious Diseases and International Medicine, University of Minnesota, 420 Delaware Street SE, MMC250, Minneapolis, MN 55455, USA.
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Xie YX, Wang Y, Huang XJ, Xu LP, Zhang XH, Liu KY, Yan CH, Wang FR, Sun YQ, Kong J, Gao YQ, Shi HY, Liu DP, Cheng YF. [Clinical analysis of hemorrhagic cystitis in children and adolescents with hematological diseases post haplo-hematopoietic stem cell transplantation]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2018; 39:833-838. [PMID: 30369205 PMCID: PMC7348279 DOI: 10.3760/cma.j.issn.0253-2727.2018.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Indexed: 11/09/2022]
Abstract
Objective: To investigate the incidence and clinical features to probe the risk factors of hemorrhagic cystitis (HC) in children and adolescents with hematological diseases post haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Medical records of 62 children and 27 adolescents with hematological diseases treated with haplo-HSCT between 2015 and 2016 were analyzed. Results: Of 89 cases (56 boys and 33 girls) , 44 patients were diagnosed with ALL, 33 AML, 3 AHL and 9 MDS. HC occurred in 32 of the 89 patients with an incidence of 36%, including 6 with grade Ⅰ, 16 with grade Ⅱ, 8 with grade Ⅲ, 2 with grade Ⅳ HC, respectively. The median time of HC onset was 25 days (range 2-55 days) after haplo-HSCT with the median duration as 19 days (range 3-95 days) , all of them were cured. The incidence of HC was lower in the group of children than that in the group of adolescents (27.4% vs 55.6%, χ(2)=6.466, P<0.05) , and the incidence of HC was higher in the group of patients who were ≥5 years old than that in the group of patients who were <5 years old (0 vs 34%, χ(2)=4.043, P<0.05) . Conclusion: HC is one of common complications in children and adolescents with hematological diseases post haplo-HSCT, older age was associated with increased mortality.
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Affiliation(s)
- Y X Xie
- Institute of Hematology, People's Hospital, Peking University, Beijing 100044, China
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Abudayyeh A, Hamdi A, Abdelrahim M, Lin H, Page VD, Rondon G, Andersson BS, Afrough A, Martinez CS, Tarrand JJ, Kontoyiannis DP, Marin D, Gaber AO, Oran B, Chemaly RF, Ahmed S, Abudayyeh I, Olson A, Jones R, Popat U, Champlin RE, Shpall EJ, Rezvani K. Poor immune reconstitution is associated with symptomatic BK polyomavirus viruria in allogeneic stem cell transplant recipients. Transpl Infect Dis 2016; 19. [PMID: 27862740 DOI: 10.1111/tid.12632] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 06/24/2016] [Accepted: 08/01/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND BK polyomavirus (BKPyV) infections are known indicators of immune suppression in hematopoietic stem cell transplant (HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction, and prolonged hospital stays. In this study, we determined transplant-associated variables and immune parameters that can predict for the risk of BKPyV viruria. We hypothesized that BKPyV infection is a marker of poor immune recovery. METHODS We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center in Houston between January 2004 and December 2012. We evaluated their immune parameters and their transplant-associated factors. BKPyV positivity was defined as BKPyV detection in urine by polymerase chain reaction testing. Cox proportional hazards model, as well as competing risk analysis method using subdistribution hazard models with death as competing risk, were applied to assess risk of BKPyV viruria. RESULTS We identified a total of 2477 patients with a median age of 52 years. BKPyV viruria was manifest in 25% (n=629) of the patients. The median time from transplantation to BKPyV viruria development was 42 days among the patients who had BKPyV viruria. On multivariate analysis, tumor type, acute GVHD, chronic GVHD, myeloablative conditioning regimen, cord blood as the graft source, CD3+ , CD4+ , CD8+ , CD56+ , NK counts, and low platelet count were shown to be significantly associated with BKPyV infection. These finding were further confirmed when models incorporating the competing risk of death yielded similar findings. CONCLUSION In this study, we report significant associations between BKPyV reactivation following allogeneic HSCT and suppressed immune variables. In addition, this study provides valuable information on the immune status of HSCT recipients as a predictor of BKPyV infections that may in turn help us formulate plans for more effective prevention and treatment of this infection.
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Affiliation(s)
- Ala Abudayyeh
- Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Amir Hamdi
- Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Maen Abdelrahim
- Division of Medical Oncology, Duke University School of Medicine, Durham, NC, USA
| | - Heather Lin
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Valda D Page
- Department of Emergency Medicine and Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Gabriela Rondon
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Borje S Andersson
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Aimaz Afrough
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Charles S Martinez
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey J Tarrand
- Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Dimitrios P Kontoyiannis
- Department of Infectious Diseases, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - David Marin
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - A Osama Gaber
- Department of Transplant Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Betul Oran
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Roy F Chemaly
- Department of Infectious Diseases, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sairah Ahmed
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Islam Abudayyeh
- Division of Cardiology, Interventional Cardiology, Loma Linda University Health, Loma Linda, CA, USA
| | - Amanda Olson
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Roy Jones
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Uday Popat
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Richard E Champlin
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Elizabeth J Shpall
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Katayoun Rezvani
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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11
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Au JK, Graziano C, Elizondo RA, Ryan S, Roth DR, Koh CJ, Gonzales ET, Tu DT, Janzen N, Naik S, Seth A. Urologic Outcomes of Children With Hemorrhagic Cystitis After Bone Marrow Transplant at a Single Institution. Urology 2016; 101:126-132. [PMID: 27793653 DOI: 10.1016/j.urology.2016.10.030] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 10/10/2016] [Accepted: 10/14/2016] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To analyze clinical outcomes and the risk factors associated with genitourinary (GU) morbidity and mortality in children who present with hemorrhagic cystitis (HC) after bone marrow transplant (BMT). METHODS A retrospective chart review of patients with HC who had undergone BMT at a single pediatric hospital from 2008 to 2015 was conducted. Demographic data, severity of hematuria, HC management, and mortality were analyzed. Bivariate analysis and binary logistic regression were performed to identify risk factors. RESULTS Out of 43 patients who met inclusion criteria, 67.4% were male with a median age at BMT of 10.2 years (interquartile range 5.8-14.6). Percutaneous nephrostomy catheters were inserted in 5 patients for urinary diversion. All-cause mortality was 32.6% (N = 14). Intravesical retroviral therapy (P <.001), HC grade (P <.001), total Foley time (P <.001), total gross hematuria time (P <.001), total days hospitalized (P = .012), and days to most improved hematuria (P = .032) were associated with significant GU morbidity on bivariate analysis. On multivariable analysis, days to most improved hematuria was associated with significant GU morbidity odds ratio of 1.177 (1.006-1.376) (P = .042). Status of percutaneous nephrostomy was not associated with increased mortality (P = .472); however, in the multivariate model, BK viremia (P = .023), need for renal dialysis (P = .003), and presence of Foley catheter (P = .005) were associated with increased mortality. CONCLUSION Children with HC after BMT fall in a very high-risk category with high mortality and significant GU morbidity. The presence of a Foley catheter, need for dialysis, and BK viremia are associated with increased mortality.
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Affiliation(s)
- Jason K Au
- Department of Pediatric Urology, Texas Children's Hospital/Baylor College of Medicine, Houston, TX
| | | | - Rodolfo A Elizondo
- Department of Pediatric Urology, Texas Children's Hospital/Baylor College of Medicine, Houston, TX
| | - Sheila Ryan
- Department of Pediatric Urology, Texas Children's Hospital/Baylor College of Medicine, Houston, TX
| | - David R Roth
- Department of Pediatric Urology, Texas Children's Hospital/Baylor College of Medicine, Houston, TX
| | - Chester J Koh
- Department of Pediatric Urology, Texas Children's Hospital/Baylor College of Medicine, Houston, TX
| | - Edmond T Gonzales
- Department of Pediatric Urology, Texas Children's Hospital/Baylor College of Medicine, Houston, TX
| | - Duong T Tu
- Department of Pediatric Urology, Texas Children's Hospital/Baylor College of Medicine, Houston, TX
| | - Nicolette Janzen
- Department of Pediatric Urology, Texas Children's Hospital/Baylor College of Medicine, Houston, TX
| | - Swati Naik
- Department of Hematology/Oncology, Texas Children's Hospital//Baylor College of Medicine, Houston, TX
| | - Abhishek Seth
- Department of Pediatric Urology, Texas Children's Hospital/Baylor College of Medicine, Houston, TX.
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12
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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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13
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Affiliation(s)
- Sangeeta Hingorani
- From the Department of Pediatrics, Division of Nephrology, University of Washington School of Medicine, and the Clinical Research Division, Fred Hutchinson Cancer Research Center - both in Seattle
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14
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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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15
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Abstract
Infections following HCT are frequently related to risk factors caused by the procedure itself. Neutropenia and mucositis predispose to bacterial infections. Prolonged neutropenia increases the likelihood of invasive fungal infection. GVHD and its treatment create the most important easily identifiable risk period for a variety of infectious complications, particularly mold infections. Profound, prolonged T cell immunodeficiency, present after T cell-depleted or cord blood transplants, is the main risk factor for viral problems like disseminated adenovirus disease or EBV-related posttransplant lymphoproliferative disorder.
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16
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Fernández-García M, Gonzalez-Vicent M, Mastro-Martinez I, Serrano A, Diaz MA. Intensive Care Unit Admissions Among Children After Hematopoietic Stem Cell Transplantation: Incidence, Outcome, and Prognostic Factors. J Pediatr Hematol Oncol 2015; 37:529-35. [PMID: 26241722 DOI: 10.1097/mph.0000000000000401] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
We retrospectively analyzed posttransplantation events in 299 children who underwent hematopoietic stem cell transplantation between 2005 and 2011 in order to ascertain the incidence of life-threatening complications requiring pediatric intensive care unit (PICU) admission, the contributing risk factors, and the patient's long-term survival. Sixty-eight patients (23%) were admitted to the PICU. Risks factors associated with higher cumulative incidence of PICU admission on univariate analysis were nonmalignant disease, status at transplantation, type of transplant, source of stem cell, engraftment syndrome (ES), veno-occlusive disease, acute graft versus host disease (GvHD), chronic GvHD, thrombotic microangiopathy, bronchiolitis obliterans, hemorrhagic cystitis, and posterior reversible encephalopathy syndrome (PRES). On multivariate analysis, only ES, acute GvHD, transplant-associated thrombotic microangiopathy (TA-TMA), and PRES were statistically significant. The variables that had a negative impact on survival, on univariate analysis, were allogeneic transplant, age, male sex, a high O-PRISM score, a high O-PRISM3 score, engraftment failure, acute GvHD, TA-TMA, hemorrhagic cystitis, and PRES. On multivariate analysis, only age, allogeneic transplant, engraftment failure, acute GvHD, TA-TMA, and hemorrhagic cystitis had a negative impact on survival. In conclusion, our report provides new findings regarding life-threatening complications after hematopoietic transplantation for PICU admission and survival after that in a pediatric population.
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Affiliation(s)
- Manuela Fernández-García
- *Department of Pediatrics, Division of Pediatric Hematology-Oncology and Hematopoietic Stem Cell Transplantation and Cell Therapy Unit †Department of Pediatrics, Division of Pediatric Intensive Care Unit, Niño Jesus Children Hospital, Madrid, Spain
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17
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Rascon J, Verkauskas G, Pasauliene R, Zubka V, Bilius V, Rageliene L. Intravesical cidofovir to treat BK virus-associated hemorrhagic cystitis in children after hematopoietic stem cell transplantation. Pediatr Transplant 2015; 19:E111-4. [PMID: 25882393 DOI: 10.1111/petr.12477] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/17/2015] [Indexed: 12/15/2022]
Abstract
HC related to BK virus replication might be a severe complication following allogeneic HSCT. There are no clearly defined treatment guidelines in pediatric population. The data on the effectiveness of ICI to manage severe bleeding in children are very limited. We report our experience of intravesical cidofovir in four children, 6-15 yr of age, to manage grade III-IV BK virus-associated HC. Three of four children had high CSA serum level prior to developing cystitis. Intravesical instillations of cidofovir resulted only in temporal relief of bleeding. After immune suppression was withdrawn or tapered, intravesical instillations of formalin solution had to be undertaken to abort severe bleeding. We concluded that intravesical cidofovir alone did not appear to be sufficiently effective in case of severe HC, necessitating complimentary procedures to stop macrohematuria.
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Affiliation(s)
- Jelena Rascon
- Center of Pediatric Oncology and Hematology, Bone Marrow Transplantation unit, Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania; Vilnius University, Vilnius, Lithuania
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18
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Abudayyeh A, Abdelrahim M. Current Strategies for Prevention and Management of Stem Cell Transplant-Related Urinary Tract and Voiding Dysfunction. CURRENT BLADDER DYSFUNCTION REPORTS 2015. [DOI: 10.1007/s11884-015-0289-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Infectious Prophylaxis in Paediatric Oncology and Stem Cell Transplantation. CURRENT PEDIATRICS REPORTS 2015. [DOI: 10.1007/s40124-015-0076-x] [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: 10/23/2022]
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20
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Kawashima N, Ito Y, Sekiya Y, Narita A, Okuno Y, Muramatsu H, Irie M, Hama A, Takahashi Y, Kojima S. Choreito Formula for BK Virus–associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2015; 21:319-25. [DOI: 10.1016/j.bbmt.2014.10.018] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Accepted: 10/21/2014] [Indexed: 10/24/2022]
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21
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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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