• 四川大學(xué)華西醫(yī)院血液內(nèi)科（成都，610041）;

【摘要】　目的　 分析異基因造血干細(xì)胞移植術(shù)（allogeneic hematopoietic stem cell transplantation，allo-HSCT）后出血性膀胱炎（hemorrhagic cystitis，HC）相關(guān)的危險因素，動態(tài)監(jiān)測受者尿BK病毒（BK virus，BKV），分析其與HC發(fā)病的關(guān)系。　方法　 回顧性分析2003年3月-2008年1月期間接受allo-HSCT的121例患者的資料，選擇8個臨床參數(shù)[年齡、性別、疾病類型、移植時疾病狀態(tài)、供者類型、預(yù)處理方案、急性移植物抗宿主?。╝cute graft-versus-host disease，aGVHD）、aGVHD的預(yù)防方案]作COX回歸分析。采用SYBR Green染料實時熒光定量聚合酶鏈反應(yīng)法對2006年9月-2008年1月42例allo-HSCT患者尿BKV載量進(jìn)行動態(tài)監(jiān)測，分析被檢查者尿液BKV基因載量與HC發(fā)生以及嚴(yán)重程度的關(guān)系。　結(jié)果　 121例患者中有24例發(fā)生HC，發(fā)病時間為術(shù)后0~63 d，中位時間40 d；持續(xù)時間7~150 d，中位時間22 d。Ⅱ~Ⅳ度aGVHD為HC的獨立危險因素[RR=8.304，95%CI（1.223，56.396），P=0.030]。allo-HSCT受者尿液中BKV檢出率為100%（42/42）。與正常人及未發(fā)生HC的allo-HSCT受者相比，HC患者尿中BKV基因載量具有更高平均峰值。　結(jié)論　 Ⅱ~Ⅳ度aGVHD，尿中BKV DNA高載量與HC的發(fā)生有相關(guān)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.

引用本文： 陳心傳,劉霆,孟文彤,賈永前,李建軍,何川,黃杰. 異基因造血干細(xì)胞移植后出血性膀胱炎的危險因素. 華西醫(yī)學(xué), 2011, 26(12): 1767-1773. doi: 復(fù)制

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. 　馬向娟, 任漢云, 邱志祥, 造血干細(xì)胞移植后出血性膀胱炎多因素分析[J]. 中國實驗血液學(xué)雜志, 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. 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. 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. 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. 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. 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. 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. 7. 　Hirsch HH, Steiger J. Polyomavirus BK[J]. Lancet Infect Dis, 2003, 3(10): 611-623.
  8. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 19. 　馬向娟, 任漢云, 邱志祥, 造血干細(xì)胞移植后出血性膀胱炎多因素分析[J]. 中國實驗血液學(xué)雜志, 2010, 18(4): 1007-1012.
  20. 20. 　Hirsch HH. BK virus: opportunity makes a pathogen[J]. Clin Infect Dis, 2005, 41(3): 354-360.
  21. 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.