儿童异基因造血干细胞移植术后迟发性出血性膀胱炎的病因学研究

Etiological Study of Late Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation in Children

目的:前瞻性研究BK病毒(BKV)与儿童allo-HSCT后迟发性出血性膀胱炎(LOHC)发生发展的相关性。方法:回顾性分析1998年1月至2016年3月在本院血液病区行allo-HSCT的276例患儿的临床资料;采用实时荧光定量PCR技术前瞻性监测该病区2015年8月至2016年3月接受allo-HSCT的23例患儿血浆及尿中BKV的DNA载量,以了解allo-HSCT患儿LOHC发生发展和BKV的相关性。结果:在276例allo-HSCT患儿中发生LOHC者67例(24.28%)。单因素分析显示,年龄≥6岁、不同病种、非血缘相关供体、预处理使用BU、合并aGVHD、Ⅲ-Ⅳ度aGVHD与LOHC的发生显著相关;多因素分析显示,年龄≥6岁(P=0.002)、预处理含BU(P=0.042)、Ⅲ-Ⅳ度aGVHD(P=0.011)是LOHC发生的独立危险因素。23例allo-HSCT患儿中10例尿检出BKV^+,其中6例发生LOHC,在LOHC^+组尿BKV^+率(85.7%)明显高于LOHC-组(25.0%)(χ~2=5.043,P=0.007)。LOHC发生率与尿BKV^+与否(r=0.564,P=0.005)、LOHC严重度与尿BKV载量分别呈正相关(r=0.502,P=0.015)。6例LOHC患儿,5例合并aGVHD,均给予加强抗病毒治疗,其中4例需给予加强免疫抑制治疗。结论:年龄≥6岁、预处理含BU及Ⅲ-Ⅳ度aGVHD是儿童异基因造血干细胞移植术后LOHC发生的独立危险因素。尿BKV阳性率与儿童异基因造血干细胞移植术后LOHC的发生呈正相关,且尿BKV载量越高,LOHC程度越严重。

Objective： To prospectively study the correlation BKV with the occurrence and development of late onset hemorrhagic cystitis（ LOHC） after allogeneic hematopoietic stem cell transplantation（ allo-HSCT）. Methods： The clinical data of a total of 276 patients with allo-HSCT in our department between January 1998 and March 2016 were analyzed ratrospectvely. Quantitative Real-time PCR assay was used to prospectively monitor the BKV DNA load of the urine and plasma for 23 patients accepting allo-HSCT from August 2015 to March 2016. Results： LOHC（ 24. 28%）occurred in 67 of 276 cases with allo-HSCT. Univariate analysis showed that age older than 6 years,different diseases,unrelated donor,pretreatment with BU,Ⅲ-Ⅳ aGVHD significantly correlated with LOHC. Multivariate analysis demonstrated that age older than 6 years（ P〈0. 01）,pretreatment with BU（ P〈0. 05）,and aGVHD of grade Ⅲ-Ⅳ（ P = 0. 011） were the independent risk factors for LOHC. Among 23 patients after allo-HSTC,10 of which were positive of urine BKV,and LOHC occurred in 6 cases. The positive rate of urine BKV（ 85. 7%） in group LOHC ＋ was significantly higher than that in the group LOHC-（ 25. 0%）（ χ2 = 5. 043,P〈0. 01）. The incidence of LOHC positively correlated with the positive rate of BKV（ r = 0. 564,P〈0. 01）,and the severity of LOHC positively correlated with urinary BKV load（ r = 0. 502,P〈0. 01）. And 5 of 6 petriatic patients with LOHC had aGVHD. All of them were subject to the strengthened antiviral treatment,and 4 of them accepted intensive immunosuppression therapy.Conclusion： Age ≥6 years old,precenditioning regieme with BU and aGVHD of grade Ⅲ-Ⅳ are independent risk factors for LOHC after allo-HSCT,the positive rate of urine BKV load positively correlates with the severity of LOHC after allo-HSCT.