两种剂量r-ATG联合CsA治疗儿童重型再生障碍性贫血的疗效比较

本研究旨在比较两组不同剂量的兔源抗胸腺球蛋白（r-ATG）联合环孢菌素A（Cs A）治疗儿童重型再生障碍性贫血（severe aplastic anemia,SAA）的疗效和安全性。回顾性分析了我院2005年1月至2013年7月接受r-ATG联合Cs A免疫抑制治疗（immunosuppressive therapy,IST）的儿童SAA 95例,其中55例的r-ATG治疗剂量为2.5 mg/（kg·d）,连用5 d（Ⅰ组）,另40例r-ATG治疗剂量为3.5 mg/（kg·d）,连用5 d（Ⅱ组）。95例患儿中男43例,女52例,年龄1-16岁。两组患儿一般临床资料具有可比性。治疗后第3、6、9、12个月评估并比较两组间治疗有效率,观察早期不良反应、早期死亡、远期克隆性疾病及复发情况。结果表明,治疗后第3、6个月,Ⅱ组的治疗反应率稍高于Ⅰ组（50%vs 32.1%,P=0.08;65%vs 45.3%,P=0.059）;第9、12个月,Ⅱ组和Ⅰ组的治疗反应率无明显差异（70.0%vs 71.1%,P=0.904;82.5%vs 80.8%,P=0.832）;第12个月,Ⅱ组完全反应率稍高于Ⅰ组（40.0%vs 23.1%,P=0.08）;第3、6、9个月两组的完全反应率差异无统计学意义;两组血清病、近期感染及早期死亡发生率差异无统计学意义,2年总体生存率差异无统计学意义。对Ⅰ组39例已随访至2年以上,有3例复发,1例确诊为急性单核细胞白血病（M5）,1例死亡。对Ⅱ组15例随访至2年以上,未出现复发、死亡及多克隆性疾病病例。结论：r-ATG联合Cs A是治疗儿童SAA的有效、安全治疗方法。r-ATG 3.5 mg（kg·d）方案6个月内疗效优于2.5 mg/（kg·d）方案,但两组最终疗效相当,且近期不良反应和早期死亡率未增加。对远期并发症的发生及长期生存率需进一步探讨比较,以便为临床选择合适的r-ATG剂量提供依据。

Comparison between Two Different Dose of r-ATG Combined with CsA for Treating Children with Severe Aplastic Anemia

This study was purposed to compare the efficacy and safety of two different doses of rabbit anti-thymocyte globulin（ r-ATG）combined with cyclosporine（CsA）for treating children with severe aplastic anemia（ SAA）.From January 2005 to July 2010 a total of 95 children with SAA accepted intensive immunosuppressive therapy（ IIST）in our departmentout of them 55 cases were treated with r-ATG 2.5 mg /（kg·d）for 5 days in combination with CsA（ groupⅠ） and other 40 cases were theated with r-ATG 3.5 mg /（kg·d）for 5 days in combination with CsA（ group Ⅱ）.The responsive rateadverse reactionsearly mortalityrelapse and clonal disease were analyzed retrospectively and results between the two groups were compared.Out of 95 patients 43 were boys and 52 were girlstheir ages were from 1 to 16 years.The sexageseverity and course of the disease were comparable between the two groups.The results showed that after treating for 3 and 6 monthsthe response of paitents in group Ⅱ was higher than that of patients in group Ⅰ（ 50% vs 32.1%P = 0.08 and 65% vs 45.3%P = 0.059）,at 9 and 12 months the response rate of patients in groupⅡ and group Ⅰ did not show significant difference（ 70.0% vs 71.1%P = 0.904 and 82.5% vs 80.8%P = 0.832）;at 12 months of treatmentthe complete response rate of patients in group Ⅱ was significantly higher than that of patients in group Ⅰ（ 40.0% vs 23.1%P = 0.08）; at 3months of treatmentthe complete response rate of 2 groups showed no obvious difference.The incidence of serum diseaseearly infection and early mortality did not show statistical difference between two groups.There was no statistical difference in 2 year overall survival rate of two groups.In groupⅠ 39 patients were followed-up for more than 2 yearsamong them 3 patients relapsed1 patient died and 1 patient was diagnosed as acute monocytic leukemia（ M5）.In group Ⅱ 15 patients were followed up for more than 2 yearsthere were no relapsedeath and clonal disease.It is concluded that the r-ATG com