儿童异基因造血干细胞移植后出血性膀胱炎早期症状与外科治疗的分析

Analysis of early clinical symptoms and surgical intervention of hemorrhagic cystitis after hematopoietic stem cell transplantation in children

目的·分析异基因造血干细胞移植(hematopoietic stem cell transplantation,HSCT)后出血性膀胱炎(hemorrhagic cystitis,HC)的早期临床症状特点及其与疾病进展之间的关系。方法·回顾性分析上海交通大学医学院附属上海儿童医学中心2013年6月至2020年12月间收治的77例接受HSCT治疗后出现HC的患儿的临床资料。每位患儿早期予以预防性应用美司钠,病程中行水化、碱化,利尿抗感染,解痉止痛治疗。对于难治性HC患儿行留置导尿膀胱灌注或膀胱镜下电凝止血,对于膀胱镜手术困难患儿行开放性膀胱造瘘联合术后膀胱灌注治疗。依据Droller标准将HC分度,记录患儿尿路刺激症状及血尿症状特点、各症状出现时间、进展至重度HC (Ⅲ~Ⅳ度HC)的时间、病程持续时间、治疗方法及治疗效果等。结果·77例患儿中,男性49例(63.6%),女性28例(36.4%),中位年龄为7 (5,11)岁;65例(84.4%)患儿病程中存在病毒感染,主要为BK多瘤病毒(BK polyomavirus,BKV)、巨细胞病毒(cytomegalovirus,CMV)以及EB病毒(EpsteinBarr virus,EBV);以尿路刺激为首发症状的患儿有45例(58.4%),以血尿为首发症状的有32例(41.6%)。以尿路刺激为首发症状的患儿经过水化、碱化、镇痛等治疗后最终均表现为不同程度的血尿,中位进展时间为2 (1,5) d,其中Ⅰ度3例(6.7%),Ⅱ度16例(35.5%),Ⅲ度23例(51.1%),Ⅳ度3例(6.7%)。手术治疗3例,1例Ⅲ度患儿行膀胱镜电凝止血治疗后完全缓解,1例Ⅳ度的患儿行开放膀胱造瘘术联合膀胱灌注治疗后症状部分缓解,1例Ⅳ度患儿膀胱镜电凝止血治疗后因多脏器功能衰竭死亡。结论·HSCT后HC患儿超过半数是以尿路刺激症状为首发症状,且超过半数的重度HC患儿的首发症状也为尿路刺激症状,该类患儿早期需要更积极的干预措施。

Objective·To analyze the characteristics of early clinical symptoms of hemorrhagic cystitis(HC) after allogeneic hematopoietic stem cell transplantation(HSCT) and the relationship between the symptoms and disease progression.Methods·The clinical data of 77 children with HC after HSCT,treated in Shanghai Children’s Medical Center,Shanghai Jiao Tong University School of Medicine from June 2013 to December 2020,were retrospectively analyzed.Each child was prophylactically applied with mesna in the early stage,and hydration,alkalization,diuretics,anti-infection agents,antispasmodic and analgesic drugs were applied during the course of disease.Moreover,indwelling catheterization and bladder perfusion or cystoscopic electrical coagulation were performed for refractory HC children;Open cystostomy combined with postoperative bladder perfusion was performed when the cystoscope was difficult to perform.HC was graded according to Droller’s standard,and the characteristics of urinary irritation symptoms and hematuria symptoms,the onset time of each symptom,the time of progression to severe HC(grade Ⅲ-Ⅳ),the duration of disease course,treatment methods and therapeutic effects were recorded.Results·Among the 77 cases,49(63.6%) were male and 28(36.4%) were female.The median age was 7(5,11) years old.Sixty-five cases(84.4%) had virus infection during the course of disease,such as BK polyomavirus(BKV),cytomegalovirus(CMV) and Epstein-Barr virus(EBV).Forty-five cases(58.4%) had urinary irritation symptoms as the first symptom of urinary tract,and 32 cases(41.6%) had hematuria.Children who had urinary irritation symptoms as the first symptom eventually developed hematuria symptoms of varying degrees after hydration,alkalization,analgesic drugs or other routine treatments,with a median interval of 2(1,5) d,including 3 cases of grade Ⅰ(6.7%),16 of grade Ⅱ(35.5%),23 of grade Ⅲ(51.1%),and 3 of grade Ⅳ(6.7%).There were 3 cases of surgical treatment:1 case of gradeⅢ was completely relieved after cystoscopic hemostatic treatment,1 case of grade Ⅳ was partially relieved after open cystostomy combined with postoperative bladder perfusion,and 1 case of grade Ⅳ died for multiple organ failure after cystoscopic hemostatic treatment.Conclusion·More than half of the children with HC after HSCT start with urinary irritation symptoms,and more than half of the children with severe HC also start with it.Such children need more active intervention measures in the early stage.