Analysis of Risk Factors for Development of Hemorrhagic Cystitis in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation_West China Medical Journal

Authors：

CHEN Xinchuan ,  LIU Ting , MENG Wentong , JIA Yongqian , LI Jianjun , HE Chuan , HUANG Jie

Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

LIU Ting, Email: xinchuan_chen@163.com

Keywords：

异基因造血干细胞移植; 迟发性出血性膀胱炎; BK病毒

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【摘要】　目的　分析异基因造血干细胞移植术（allogeneic hematopoietic stem cell transplantation，allo-HSCT）后出血性膀胱炎（hemorrhagic cystitis，HC）相关的危险因素，动态监测受者尿BK病毒（BK virus，BKV），分析其与HC发病的关系。　方法　回顾性分析2003年3月-2008年1月期间接受allo-HSCT的121例患者的资料，选择8个临床参数[年龄、性别、疾病类型、移植时疾病状态、供者类型、预处理方案、急性移植物抗宿主病（acute graft-versus-host disease，aGVHD）、aGVHD的预防方案]作COX回归分析。采用SYBR Green染料实时荧光定量聚合酶链反应法对2006年9月-2008年1月42例allo-HSCT患者尿BKV载量进行动态监测，分析被检查者尿液BKV基因载量与HC发生以及严重程度的关系。　结果　 121例患者中有24例发生HC，发病时间为术后0~63 d，中位时间40 d；持续时间7~150 d，中位时间22 d。Ⅱ~Ⅳ度aGVHD为HC的独立危险因素[RR=8.304，95%CI（1.223，56.396），P=0.030]。allo-HSCT受者尿液中BKV检出率为100%（42/42）。与正常人及未发生HC的allo-HSCT受者相比，HC患者尿中BKV基因载量具有更高平均峰值。　结论　 Ⅱ~Ⅳ度aGVHD，尿中BKV DNA高载量与HC的发生有相关性。
【Abstract】　Objective　 To identify the risk factors for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and define the quantitative relationship between BK virus (BKV) DNA load with HC.　Methods　 The medical records of 121 patients undergoing allo-HSCT from March 2003 to January 2008 were retrospectively analyzed. Eight clinical parameters were selected for COX regression analysis, including age, sex, underlying disease, disease status at transplant, donor type, conditioning regimen, acute graft-versus-host disease (aGVHD), and GVHD prophylaxis. From September 2006 to January 2008, mid-stream urine samples were continuously collected from 42 patients with allo-HSCT. SYBR green real-time polymerase chain reaction, technique was utilized to define the quantitative relationship between BKV DNA load and HC.　Results　 Twenty-four out of 121 patients developed HC. The median time of onset was 40 days after HSCT, ranged from 0 to 63 days. The disease lasted for 7 to 150 days, with a median duration of 22 days. Grade Ⅱ-Ⅳ aGVHD [RR=8.304, 95% CI (1.223,56.396); P=0.030] was identified as an independent risk factor for the occurrence of HC. BKV excretion was detected in 100% (42/42) of the recipients of allo-HSCT. When compared with asymptomatic patients and allo-HSCT recipients without HC, patients with HC had a significantly higher mean peak BKV DNA load.　Conclusions　 Patients are at an increased risk of developing HC if they have grade Ⅱ-Ⅳ aGVHD. A correlation between the load of BKV and incidence of HC may exist.

Citation： CHEN Xinchuan,LIU Ting,MENG Wentong,JIA Yongqian,LI Jianjun,HE Chuan,HUANG Jie. Analysis of Risk Factors for Development of Hemorrhagic Cystitis in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation. West China Medical Journal, 2011, 26(12): 1767-1773. doi: Copy

1.	Sencer SF, Haake RJ, Weisdorf DJ. Hemorrhagic cystitis after bone marrow transplantation. Risk factors and complications[J]. Transplantation, 1993, 56(4): 875-879.
2.	Bedi A, Miller CB, Hanson JL, et al. Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation[J]. J Clin Oncol, 1995, 13(5): 1103-1109.
3.	Russell SJ, Vowels MR, Vale T. Haemorrhagic cystitis in paediatric bone marrow transplant patients: an association with infective agents, GVHD and prior cyclophosphamide[J]. Bone Marrow Transplant, 1994, 13(5): 533-539.
4.	Arthur RR, Shah KV, Baust SJ, et al. Association of BK viruria with hemorrhagic cystitis in recipients of bone marrow transplants[J]. N Engl J Med, 1986, 315(4): 230-234.
5.	Azzi A, Cesaro S, Laszlo D, et al. Human polyomavirus BK(BKV)load and haemorrhagic cystitis in bone marrow transplantation patients[J]. J Clin Virol, 1999, 14(2): 79-86.
6.	Held TK, Biel SS, Nitsche A, et al. Treatment of BK virus-associated hemorrhagic cystitis and simultaneous CMV reactivation with cidofovir[J]. Bone Marrow Transplant, 2000, 26(3): 347-350.
7.	Hirsch HH, Steiger J. Polyomavirus BK[J]. Lancet Infect Dis, 2003, 3(10): 611-623.
8.	Leung AY, Yuen KY, Kwong YL. Polyoma BK virus and haemorrhagic cystitis in haematopoietic stem cell transplantation: a changing paradigm[J]. Bone Marrow Transplant, 2005, 36(11): 929-937.
9.	Leung AY, Suen CK, Lie AK, et al. Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation[J]. Blood, 2001, 98(6): 1971-1978.
10.	Xu LP, Zhang HY, Huang XJ, et al. Hemorrhagic cystitis following hematopoietic stem cell transplantation: incidence, risk factors and association with CMV reactivation and graft-versus-host disease[J]. Chin Med J(Engl), 2007, 120(19): 1666-1671.
11.	Apperley JF, Rice SJ, Bishop JA, et al. Late-onset hemorrhagic cystitis associated with urinary excretion of polyomaviruses after bone marrow transplantation[J]. Transplantation,1987, 43(1): 108-112.
12.	Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading[J]. Bone Marrow Transplant, 1995, 15(6): 825-828.
13.	Tsuboi K, Kishi K, Ohmachi K, et al. Multivariate analysis of risk factors for hemorrhagic cystitis after hematopoietic stem cell transplantation[J]. Bone Marrow Transplant, 2003, 32(9): 903-907.
14.	Cesaro S, Brugiolo A, Faraci M, et al. Incidence and treatment of hemorrhagic cystitis in children given hematopoietic stem cell transplantation: a survey from the Italian association of pediatric hematology oncology-bone marrow transplantation group[J]. Bone Marrow Transplant, 2003, 32(9): 925-931.
15.	Seber A, Shu XO, Defor T, et al. Risk factors for severe hemorrhagic cystitis following BMT[J]. Bone Marrow Transplant, 1999, 23(1): 35-40.
16.	Giraud G, Bogdanovic G, Priftakis P, et al. The incidence of hemorrhagic cystitis and BK-viruria in allogeneic hematopoietic stem cell recipients according to intensity of the conditioning regimen[J]. Haematologica, 2006, 91(3): 401-404.
17.	Giraud G, Priftakis P, Bogdanovic G, et al. BK-viruria and haemorrhagic cystitis are more frequent in allogeneic haematopoietic stem cell transplant patients receiving full conditioning and unrelated-HLA-mismatched grafts[J]. Bone Marrow Transplant, 2008, 41(8): 737-742.
18.	El-Zimaity M, Saliba R, Chan K, et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters[J]. Blood, 2004, 103(12): 4674-4680.
19.	马向娟, 任汉云, 邱志祥, 造血干细胞移植后出血性膀胱炎多因素分析[J]. 中国实验血液学杂志, 2010, 18(4): 1007-1012.
20.	Hirsch HH. BK virus: opportunity makes a pathogen[J]. Clin Infect Dis, 2005, 41(3): 354-360.
21.	Silva Lde P, Patah PA, Saliba RM, et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type[J]. Haematologica, 95(7): 1183-1190.

1. 　Sencer SF, Haake RJ, Weisdorf DJ. Hemorrhagic cystitis after bone marrow transplantation. Risk factors and complications[J]. Transplantation, 1993, 56(4): 875-879.
2. 　Bedi A, Miller CB, Hanson JL, et al. Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation[J]. J Clin Oncol, 1995, 13(5): 1103-1109.
3. 　Russell SJ, Vowels MR, Vale T. Haemorrhagic cystitis in paediatric bone marrow transplant patients: an association with infective agents, GVHD and prior cyclophosphamide[J]. Bone Marrow Transplant, 1994, 13(5): 533-539.
4. 　Arthur RR, Shah KV, Baust SJ, et al. Association of BK viruria with hemorrhagic cystitis in recipients of bone marrow transplants[J]. N Engl J Med, 1986, 315(4): 230-234.
5. 　Azzi A, Cesaro S, Laszlo D, et al. Human polyomavirus BK(BKV)load and haemorrhagic cystitis in bone marrow transplantation patients[J]. J Clin Virol, 1999, 14(2): 79-86.
6. 　Held TK, Biel SS, Nitsche A, et al. Treatment of BK virus-associated hemorrhagic cystitis and simultaneous CMV reactivation with cidofovir[J]. Bone Marrow Transplant, 2000, 26(3): 347-350.
7. 　Hirsch HH, Steiger J. Polyomavirus BK[J]. Lancet Infect Dis, 2003, 3(10): 611-623.
8. 　Leung AY, Yuen KY, Kwong YL. Polyoma BK virus and haemorrhagic cystitis in haematopoietic stem cell transplantation: a changing paradigm[J]. Bone Marrow Transplant, 2005, 36(11): 929-937.
9. 　Leung AY, Suen CK, Lie AK, et al. Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation[J]. Blood, 2001, 98(6): 1971-1978.
10. 　Xu LP, Zhang HY, Huang XJ, et al. Hemorrhagic cystitis following hematopoietic stem cell transplantation: incidence, risk factors and association with CMV reactivation and graft-versus-host disease[J]. Chin Med J(Engl), 2007, 120(19): 1666-1671.
11. 　Apperley JF, Rice SJ, Bishop JA, et al. Late-onset hemorrhagic cystitis associated with urinary excretion of polyomaviruses after bone marrow transplantation[J]. Transplantation,1987, 43(1): 108-112.
12. 　Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading[J]. Bone Marrow Transplant, 1995, 15(6): 825-828.
13. 　Tsuboi K, Kishi K, Ohmachi K, et al. Multivariate analysis of risk factors for hemorrhagic cystitis after hematopoietic stem cell transplantation[J]. Bone Marrow Transplant, 2003, 32(9): 903-907.
14. 　Cesaro S, Brugiolo A, Faraci M, et al. Incidence and treatment of hemorrhagic cystitis in children given hematopoietic stem cell transplantation: a survey from the Italian association of pediatric hematology oncology-bone marrow transplantation group[J]. Bone Marrow Transplant, 2003, 32(9): 925-931.
15. 　Seber A, Shu XO, Defor T, et al. Risk factors for severe hemorrhagic cystitis following BMT[J]. Bone Marrow Transplant, 1999, 23(1): 35-40.
16. 　Giraud G, Bogdanovic G, Priftakis P, et al. The incidence of hemorrhagic cystitis and BK-viruria in allogeneic hematopoietic stem cell recipients according to intensity of the conditioning regimen[J]. Haematologica, 2006, 91(3): 401-404.
17. 　Giraud G, Priftakis P, Bogdanovic G, et al. BK-viruria and haemorrhagic cystitis are more frequent in allogeneic haematopoietic stem cell transplant patients receiving full conditioning and unrelated-HLA-mismatched grafts[J]. Bone Marrow Transplant, 2008, 41(8): 737-742.
18. 　El-Zimaity M, Saliba R, Chan K, et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters[J]. Blood, 2004, 103(12): 4674-4680.
19. 　马向娟, 任汉云, 邱志祥, 造血干细胞移植后出血性膀胱炎多因素分析[J]. 中国实验血液学杂志, 2010, 18(4): 1007-1012.
20. 　Hirsch HH. BK virus: opportunity makes a pathogen[J]. Clin Infect Dis, 2005, 41(3): 354-360.
21. 　Silva Lde P, Patah PA, Saliba RM, et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type[J]. Haematologica, 95(7): 1183-1190.

West China Medical Journal

Analysis of Risk Factors for Development of Hemorrhagic Cystitis in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

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