异基因造血干细胞移植后巨细胞病毒及多瘤病毒感染相关临床特征
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摘要
目的探讨异基因造血干细胞移植(allo-HSCT)术后人巨细胞病毒(HCMV)和多瘤病毒(BKV和JCV)感染相关临床特征。方法收集2016年6月—2017年12月共53例行allo-HSCT的恶性血液病患者临床资料。移植当天开始监测患者外周血与尿的HCMV、BKV和JCV核酸载量,每周一次至100 d。分析病毒感染的发生率、发生时间、相关临床表现及危险因素。结果 51例患者发生病毒感染,感染率为96.23%。其中,HCMV感染率为54.72%(29/53)、BKV感染率为77.36%(41/53)、JCV感染率为28.30%(15/53)。肺部感染、急性移植物抗宿主病(aGVHD)和出血性膀胱炎(HC)的发生率分别为54.72%、58.49%和20.75%。危险因素分析显示:发生aGVHD(OR=24.61,95%CI:2.30～46.24)、预处理采用全身照射(OR=33.39,95%CI:1.57～79.13)及使用ATG(OR=24.77,95%CI:1.16～52.58)是影响HCMV血症的独立危险因素,HLA全相合(OR=0.003,95%CI:0.00～0.10)可降低发生HCMV血症的风险;预处理采用全身照射(OR=15.10,95%CI:1.14～39.27)是影响BKV尿症的独立危险因素,供受者血型相合(OR=0.07,95%CI:0.01～0.64)可降低发生BKV尿症的风险。结论移植术后应尽早监测受者血及尿中HCMV及多瘤病毒感染情况,以期及时预防及减少并发症的发生。
Objective To explore clinical characteristics of human cytomegalovirus(HCMV)and polyomavirus(BKV and JCV)infection after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods Clinical data of 53 patients with hematologic malignancies who underwent allo-HSCT from June 2016 to December 2017 were collected.HCMV,BKV and JCV loads in patients' peripheral blood and urine were monitored once a week from day 1 to day 100 after transplantation.Incidence,occurrence time,clinical manifestations,and risk factors of viral infection were analyzed.Results A total of 51 patients had viral infection,infection rate was 96.23%.HCMV,BKV,and JCV infection rates were 54.72%(29/53),77.36%(41/53),and 28.30%(15/53)respectively.Incidences of pulmonary infection,acute graft-versus-host disease(aGVHD),and hemorrhagic cystitis(HC)were 54.72%,58.49%,and 20.75%respectively.Analysis on risk factors showed that aGVHD(OR,24.61[95% CI,2.30-46.24]),pretreatment with total body irradiation(TBI)(OR,33.39[95% CI,1.57-79.13]),and use of antithymocyte globulin(ATG)(OR,24.77[95% CI,1.16-52.58])were independent risk factors affecting HCMV.Human leukocyte antigen(HLA)coincidence(OR,0.003[95% CI,0.00-0.10])could reduce the risk of HCMV viruria;pretreatment with TBI(OR,15.10[95% CI,1.14-39.27])was an independent risk factor for BKV viruria,compatible blood group of donor and recipient(OR,0.07[95% CI,0.01-0.64])could reduce the risk of BKV viruria.Conclusion HCMV and polyomavirus infection in blood and urine of recipient should be monitored as soon as possible after transplantation,so as to prevent and reduce complications in time.
Objective To explore clinical characteristics of human cytomegalovirus(HCMV)and polyomavirus(BKV and JCV)infection after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods Clinical data of 53 patients with hematologic malignancies who underwent allo-HSCT from June 2016 to December 2017 were collected.HCMV,BKV and JCV loads in patients' peripheral blood and urine were monitored once a week from day 1 to day 100 after transplantation.Incidence,occurrence time,clinical manifestations,and risk factors of viral infection were analyzed.Results A total of 51 patients had viral infection,infection rate was 96.23%.HCMV,BKV,and JCV infection rates were 54.72%(29/53),77.36%(41/53),and 28.30%(15/53)respectively.Incidences of pulmonary infection,acute graft-versus-host disease(aGVHD),and hemorrhagic cystitis(HC)were 54.72%,58.49%,and 20.75%respectively.Analysis on risk factors showed that aGVHD(OR,24.61[95% CI,2.30-46.24]),pretreatment with total body irradiation(TBI)(OR,33.39[95% CI,1.57-79.13]),and use of antithymocyte globulin(ATG)(OR,24.77[95% CI,1.16-52.58])were independent risk factors affecting HCMV.Human leukocyte antigen(HLA)coincidence(OR,0.003[95% CI,0.00-0.10])could reduce the risk of HCMV viruria;pretreatment with TBI(OR,15.10[95% CI,1.14-39.27])was an independent risk factor for BKV viruria,compatible blood group of donor and recipient(OR,0.07[95% CI,0.01-0.64])could reduce the risk of BKV viruria.Conclusion HCMV and polyomavirus infection in blood and urine of recipient should be monitored as soon as possible after transplantation,so as to prevent and reduce complications in time.
引文
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[15]于迪,闫志凌,徐开林.异基因造血干细胞移植中急性移植物抗宿主病的影响因素[J].国际输血及血液学杂志,2017,40(3):191-196.
[16]Ruggeri A,Roth-Guepin G,Battipaglia G,et al.Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients[J].Transpl Infect Dis,2015,17(6):822-830.
[17]Bogdanovic G,Priftakis P,Giraud G,et al.Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation[J].J Clin Microbiol,2004,42(11):5394-5396.
[18]Hingorani S.Renal complications of hematopoietic-cell transplantation[J].N Engl J Med,2016,374(23):2256-2267.
[19]Schmidt-Hieber M,Schwarck S,Stroux A,et al.Immune reconstitution and cytomegalovirus infection after allogeneic stem cell transplantation:the important impact of in vivo T cell depletion[J].Int J Hematol,2010,91(5):877-885.
[20]汪生,刘丹波,郑晓丽,等.不同方式的造血干细胞移植术后巨细胞病毒感染的临床分析[J].中国实验血液学杂志,2015,23(5):1438-1444.
[21]Adrianzen Herrera D,Ayyappan S,Jasra S,et al.Characteristics and outcomes of progressive multifocal leukoencephalopathy in hematologic malignancies and stem cell transplant-a case series[J].Leuk Lymphoma,2018[Epub ahead of print].
[22]Marty FM,Ljungman P,Chemaly RF,et al.Letermovir prophylaxis for Cytomegalovirus in hematopoietic-cell transplantation[J].N Engl J Med,2017,377(25):2433-2444.
[2]Mani J,Jin N,Schmitt M.Cellular immunotherapy for patients with reactivation of JC and BK polyomaviruses after transplantation[J].Cytotherapy,2014,16(10):1325-1335.
[3]Gomes de Oliveira PG,Ueda MY,Real JM,et al.Simultaneous quantification of the 8 human herpesviruses in allogeneic hematopoietic stem cell transplantation[J].Transplantation,2016,100(6):1363-1370.
[4]Muftuoglu M,Olson A,Marin D,et al.Allogeneic BK virusspecific T cells for progressive multifocal leukoencephalopathy[J].N Engl J Med,2018,379(15):1443-1451.
[5]Watanabe M,Kanda J,Hishizawa M,et al.Lymphocyte area under the curve as a predictive factor for viral infection after allogenic hematopoietic stem cell transplantation[J].Biol Blood Marrow Transplant,2018[Epub ahead of print].
[6]Wieruszewski PM,Herasevich S,Gajic O,et al.Respiratory failure in the hematopoietic stem cell transplant recipient[J].World J Crit Care Med,2018,7(5):62-72.
[7]Arber DA,Orazi A,Hasserjian R,et al.The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J].Blood,2016,127(20):2391-2405.
[8]Gea-Banacloche J.Pulmonary infectious complications after hematopoietic stem cell transplantation:apractical guide to clinicians[J].Curr Opin Organ Transplant,2018,23(4):375-380.
[9]中华医学会呼吸病学分会.中国成人社区获得性肺炎诊断和治疗指南(2016年版)[J].中华结核和呼吸杂志,2016,39(4):253-279.
[10]Przepiorka D,Weisdorf D,Martin P,et al.1994 Consensus conference on acute GVHD grading[J].Bone Marrow Transplant,1995,15(6):825-828.
[11]Gorczynska E,Turkiewicz D,Rybka K,et al.Incidence,clinical outcome,and management of virus-induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation[J].Biol Blood Marrow Transplant,2005,11(10):797-804.
[12]Atilla E,Yalciner M,Atilla PA,et al.Is cytomegalovirus a risk factor for haemorrhagic cystitis in allogeneic haematopoietic stem cell transplantation recipients?[J].Antivir Ther,2018[Epub ahead of print].
[13]Avery RK,Silveira FP,Benedict K,et al.Cytomegalovirus infections in lung and hematopoietic cell transplant recipients in the Organ Transplant Infection Prevention and Detection Study:A multi-year,multicenter prospective cohort study[J].Transpl Infect Dis,2018,20(3):e12877.
[14]王文辉.异基因外周血造血干细胞移植后病毒感染的临床分析[D].新疆:新疆医科大学,2013.
[15]于迪,闫志凌,徐开林.异基因造血干细胞移植中急性移植物抗宿主病的影响因素[J].国际输血及血液学杂志,2017,40(3):191-196.
[16]Ruggeri A,Roth-Guepin G,Battipaglia G,et al.Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients[J].Transpl Infect Dis,2015,17(6):822-830.
[17]Bogdanovic G,Priftakis P,Giraud G,et al.Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation[J].J Clin Microbiol,2004,42(11):5394-5396.
[18]Hingorani S.Renal complications of hematopoietic-cell transplantation[J].N Engl J Med,2016,374(23):2256-2267.
[19]Schmidt-Hieber M,Schwarck S,Stroux A,et al.Immune reconstitution and cytomegalovirus infection after allogeneic stem cell transplantation:the important impact of in vivo T cell depletion[J].Int J Hematol,2010,91(5):877-885.
[20]汪生,刘丹波,郑晓丽,等.不同方式的造血干细胞移植术后巨细胞病毒感染的临床分析[J].中国实验血液学杂志,2015,23(5):1438-1444.
[21]Adrianzen Herrera D,Ayyappan S,Jasra S,et al.Characteristics and outcomes of progressive multifocal leukoencephalopathy in hematologic malignancies and stem cell transplant-a case series[J].Leuk Lymphoma,2018[Epub ahead of print].
[22]Marty FM,Ljungman P,Chemaly RF,et al.Letermovir prophylaxis for Cytomegalovirus in hematopoietic-cell transplantation[J].N Engl J Med,2017,377(25):2433-2444.