异基因造血干细胞移植后并发出血性膀胱炎的高危因素和防治措施

Hemorrhagic cystitis following hematopoietic stem cell transplantation： risk factors and prophylaxis measures

目的评估改良的水化碱化方案对预防和治疗非亲缘异基因造血干细胞移植（URI〉HSCT）后出血性膀胱炎（HC）的效果及安全性，探讨URD-HSCT后并发HC的危险因素。方法151例血液系统恶性疾病患者接受了URD-HSCT，所有患者移植前均接受白消安＋环磷酰胺（BuCy2）方案预处理。在使用环磷酰胺（Cy）过程中，所有患者均接受改良的水化碱化输液方案，分别在静脉滴注Cy后0、3、6、9、1,2h分5次静脉注射美司钠，总量为Cy总量的120％～160％；于开始使用Cy时至结束后24h（共计72h）经中心静脉持续输液，输液量5000ml·m^-2·d^-1，匀速输注，每500ml液体中加入50g／L碳酸氢钠20ml，间断应用利尿剂，保持液体出入量平衡；每小时测尿pH值，保持尿pH值〉7．5。结果URD-HSCT后共有26例患者发生HC，发生率为17．2％（26／151），中位发病时间为40d（8-89d），无患者发生早发性HC。移植后26例HC患者再次接受改良的水化碱化尿液治疗，部分患者接受膀胱持续冲洗，所有患者均治愈，无患者因HC而死亡。经统计分析表明，以下因素与HC的发病明显相关：男性患者，相关系数（OR）值=3．093，95％可信区间（CI）为1．145-8．353，P〈0．05；急性GVHD，0R值=18．044，95％CI为3．952-82．392，P〈0．01；≥30岁，OR值=6．077，95％CI为1．585～23．299，P〈0．01。结论改良的水化碱化方案是预防和治疗URD-HSCT后HC的安全有效的措施，尤其是由Cy预处理引起的早发性HC；男性患者、年龄≥30岁以及移植后并发急性GVHD是引起HC的危险因素。

Objective To investigate the efficacy and safety of the optimal alkalized hydration solution for hemorrhagic cystitis （HC） following unrelated donor allogeneic hematopoietic stem cell transplantation （URD-HSCT）, and the risk factors and prophylaxis measures about HC. Methods The clinical data of 151 HC patients who underwent URD-HSCT were retrospectively analyzed. All patients were given busulfan/cyclophosphamide （BuCy）-based conditioning regimen. During Cy therapy, all patients were given the optimal alkalized hydration solution to prevent HC. MESNA was given intravenously after administration of Cy at 0, 3, 6, 9, 12 h, and its total dose was 120 % - 160 % of Cy. All patients were given intravenous fluid at 5000 ml·m^-2·d^-1 from administration of Cy to 24 h under the ECG monitoring. Each 500 ml liquid contained 50 g/L sodium bicarbonate 20 ml. Urinary pH value was monitored every one hour （keeping urine pH〉7. 5）. Results None of early onset HC occurred. Twenty-six of 151 （17. 2 %） patients developed late onset HC, and the median onset time was 40 （8~89） days after transplantation. During the therapy, no symptoms of the circulatory system, no congestive heart failure and no acid-base electrolyte imbalance occurred. All HC patients after rehydration, diuretic, and （or） continuous bladder irrigation and other indwelling catheter after treatment, were cured. The statistical analysis showed that the following factors were significantly associated with HC： male （OR= 3. 093, 95 % CI, 1. 145-8. 353, P〈0. 05）, acute graft versus host disease （aGVHD） （OR= 18. 044, 95 % CI, 3. 952-82. 392, P〈0.01）, and ≥30-year- old （OR= 6. 077, 95 % CI, 1. 585-23. 299, P〈0. 01）. Conclusion The optimal alkalized hydration solution is safe and effective to prevent early onset HC following URD-HSCT in combination with BuCy regimen. Male, aGVHD and ≥30-year-old were the risk factors for HC.