儿童造血干细胞移植并发出血性膀胱炎的危险因素分析与防治研究

目的观察儿童造血干细胞移植（HSCT）中出血性膀胱炎（HC）的发病情况,探讨其发病危险因素和防治策略。方法回顾分析1998年10月—2004年6月本移植中心完成的53例儿童HSCT的临床资料,其中脐血移植（UCBT）37例,外周血造血干细胞移植（PBSCT）16例。HC的预防分为2组：（1）常规组（15例）,采用水化、碱化尿液、强力利尿和巯乙磺酸钠（Mesna）;（2）前列腺素E1（PGE1）组（38例）,在常规组的基础上加用PGE1。结果53例中发生HC11例（21％）,其中Ⅰ度2例（2／11,18％）,Ⅱ度4例（4／11,36％）,Ⅲ度5例（5／11,46％）;11例HC中,早发性4例（36％）,迟发性7例（64％）。HC发病时间为＋2d-＋25d（中位时间＋15d,移植后为“＋”）。15例常规预防组中发生HC2例（13％）,38例PGE1组中发生9例（24％,P〉0．05）。单因素分析显示,受者移植年龄≥6岁、预防移植物宿主病（GVHD）阳性、巨细胞病毒（CMV）感染组的HC发生率分别高于年龄〈6岁（32％vs8％,χ^2=4．68,P〈0．05）、GVHD阴性（35％vs7％,χ^2=5．96,P〈0．05）、CMV未感染组（62％vs 13％,χ^2=7．22,P〈0．05）。logistic回归分析表明,HC发病仅与年龄（OR=3．53,P〈0．05）和CMV感染（OR=4．31,P〈0．05）有显著的相关性。采用充分水化、碱化尿液、选择性输注血小板、抗病毒和尿道膀胱冲洗等综合性治疗,全部病例均获得治愈。结论受者移植年龄≥6岁和CMV感染是儿童HSCT并发HC的重要危险因素,PGE1不能降低HC的发生。儿童HSCT后HC预后多良好。

Risk factors and treatment of hemorrhagic cystitis in children after hematopoietic stem cell transplantation

OBJECTIVE: Hemorrhagic cystitis (HC) is one of the common complications of hematopoietic stem cell transplantation (HSCT), which causes significant pain, prolongs hospitalization, and occasionally results in renal failure and death. This study aimed at investigating the incidence, risk factors, and outcome of HC in children post umbilical cord blood transplantation (UCBT) and peripheral blood stem cell transplantation (PBSCT). METHODS: From October 1998 to June the clinical records of 53 pediatric patients (aged 2-18 years with median age of 7.5 years) in our HCST center who underwent UCBT (n = 37) and PBSCT (n = 16) were retrospectively analyzed. Thirty out of 53 patients were diagnosed as hereditary hemolytic anemia (56.6%), and the others as haematological malignancies (43.4%): of whom 8 had acute lymphoblastic leukemia, 12 acute myeloid leukemia, 2 chronic myeloid leukemia and 1 non-hodgkin lymphoma. Conditioning regimen varied according to disease and clinical status, however based on cyclophosphamide (CTX, 120-200 mg/kg) and busulphan (BU, 12-16 mg/kg) in the cohort. Total body irradiation (TBI) or total lymphoid irradiation was added in 7 patients respectively. The patients were divided into regular treatment group (RTG) with 15 cases who received hyperhydration, alkalinizing, diuresis and Mesna during CTX infusion and prostaglandin E1 (PGE1) group (PEG) with 38 cases who received hyperhydration, alkalinizing, diuresis and Mesna plus prostaglandin E1 (0.03 microg/kg.h). The risk factors of HC were examined by univariate and multivariate analysis. RESULTS: In all, 11 of the 53 transplanted patients developed HC (21%) with a median onset time of day +15 (rage day +2 - +25). HC was classified as early in 4 (36%) and late in 7 (64%), and scored as grade Iin 2 cases (18%), grade II in 4 (36%) and grade III in 5 (46%). There was no significant difference between RTG and PEG in the incidence of HC, however, the incidence was much higher in the group of patients who were > or = 6 years old, positive group of graft-versus-host disease (GVHD) and group of cytomegalovirus (CMV) infection than that in the group of patients who were < 6 years of age (32% vs. 8%, P < 0.05), negative group of GVHD (35% vs. 7%, P < 0.05) and CMV non-infected group (62% vs. 13%, P < 0.05), respectively. Furthermore, by multivariate analysis, > or = 6 years old (OR = 3.53, P < 0.05) and CMV infection (OR = 4.31, P < 0.05) were significant risk factors for HC. Three of 11 patients were treated with bladder irrigation. All patients recovered from HC in a median 12.8 days (range 2-53 days). CONCLUSION: Older age (> or = 6 years) as well as CMV infection were the risk factors of HC. Both hyperhydration and Mesna were effective in preventing HC, while addition of PGE1 could not reduce the incidence of HC. The prognosis of HC in children post HSCT was satisfactory.