两种方案治疗182例郎格汉斯细胞组织细胞增生症的历史对照研究

目的：比较复旦大学附属儿科医院（我院）CHFU-LCH 2006方案（简称2006方案）和CHFU-LCH 2012方案（简称2012方案）治疗郎格汉斯细胞组织细胞增生症（LCH）患儿的疗效和不良反应。方法：2006年1月1日至2012年11月31日在我院接受2006方案治疗的LCH初治患儿纳入2006组， 2012年12月1日至2015年12月31日在我院接受2012方案治疗的LCH初治患儿纳入2012组。两组均经病理确诊LCH，排除治疗6周内自动终止治疗者。每组进一步分为单系统LCH（SS-LCH）和多系统LCH（MS-LCH）亚组。所有患儿随访至2017年3月31日。治疗有效为无活动性病变或活动性病变好转。以Kaplan-Meier法计算5年预计总生存率（OS）和无病生存率（EFS）。不良反应根据WHO急性和亚急性毒性反应分级标准分为0~4级。比较两组治疗6和12周有效率，恶化、复发和死亡情况，5年预计OS、EFS和不良反应发生情况。结果：96例患儿进入2006组，男64例，女32例，中位年龄3.4岁，中位随访时间6.9年；86例患儿进入2012组，男59例，女27例，中位年龄2.9岁，中位随访时间4.0年。两组性别、诊断年龄、临床分型和危险器官受累（RO+）情况差异无统计学意义。①2006组和2012组比较，SS-LCH、MS-LCH亚组治疗6、12周，有效率和复发率差异均无统计学意义。②2006组和2012组MS-LCH亚组分别有4例和5例退出方案，转入其他挽救方案,分别有5例和4例死亡。③两组MS-LCH患儿共93例，其中＜2岁5年预计EFS和OS均明显低于≥2岁患儿［EFS：（41.9±8.1）% vs（ 62.6±7.5）%，OS：（80.8±6.2）% vs （98.0±2.0）%］，P均＜0.05；RO+患儿5年预计EFS和OS低于RO-患儿［EFS：（37.4±8.0）% vs （66.0±7.3）%，OS：（80.4±6.3）% vs （98.0±2.0）%］，P均＜0.05；RO-患儿＜2岁和≥2岁5年预计EFS和OS差异无统计学意义；6周治疗无效患儿5年预计EFS 低于6周治疗有效患儿［（33.1±7.9）% vs （70.8±7.2）%］，P＜0.05。④2006组和2012组SS-LCH亚组5年预计EFS分别为（84.8±5.3）%和（86.7±5.6）%，5年预计OS均为100%；MS-LCH亚组5年预计EFS分别为（50.0±7.1）%和（53.2±10.0）%， 5年预计OS分别为（90.0±4.1）%和（90.6±4.5）%；差异均无统计学意义。⑤2006组MS-LCH亚组化疗相关3/4级不良反应发生率（50.0%，25/50）高于2012组（23.3%，10/43），P=0.008 0。结论：CHFU-LCH 2012方案与2006方案疗效未发现有差别，化疗相关严重不良反应较轻，MS-LCH的5年EFS仍不满意。RO+和治疗6周反应情况是MS-LCH的重要预后影响因素。

Historical control study of 182 patients with Langerhans cell histiocytosis treated with two protocols

Objective To describe the growth velocity percentile curves under breast feeding for 3 months for healthy breastfed infants aged 1 to 2 months,which can provide a more comprehensive reference for the evaluation of infant growth and development.Methods A multi-center randomized clinical trial was performed.1~2 months old infants(gestational age ≥37 weeks)fed with formula milk only for mothers' own problems presented in child health clinics of six study settings were included in formula powder group(and then randomly assigned to commercially available formula subgroup 1 or commercially available formula subgroup 2);In the same study setting,1~2 months old infants(gestational age ≥37 weeks)with exclusively breast feeding matched by gender and body weight with formula powder group were included in breast feeding group.The primary outcomes were growth velocity of height,body weight and head circumference at 1,2 and 3 months.The monthly growth velocity was equal to (measured value at this actual follow-up time-measured value at last actual follow-up time)/(this actual follow-up time-the last actual follow-up time)d] ×30.The secondary outcomes were ①the stool character and defecation frequency at the enrolment and 1,2 and 3 months after enrolment.The parents collected fresh stool and snapped photos on their phones and the stool characters were judged according to Bristol stool shape chart.②Incidence of adverse events and serious adverse events over the trial period.Full analysis set(FAS)for effectiveness analysis and evaluation of defecation frequency and stool character and safety set(SS)for adverse events were performed.The coefficient of skewness-median-coefficient of variation(LMS)method was applied to calculate smoothed height,body weight and head circumference percentiles(P3、P5、P10、P25、P50、P75、P90、P95、P97)at 1,2,3 months by LMS software.Results From May 6,2016 to October 30,2016,152 infants were included in formula powder group and 72 in breast feeding group respectively(SS).The numbers of drop-out were 24 in formula powder group and 3 in breast feeding group.The numbers of participants included in FAS were 128 for formula powder group and 69 for breast feeding group respectively.There was no significant difference in gender,day age at enrolment,height,body weight,gestational age and delivery mode between two groups(FAS).①In breast feeding group,the growth velocity of height was 3.1±1.4 cm at 1 month,3.0±0.8 cm at 2 months and 2.7±0.6 cm at 3 months,which showed a downward trend month by month;the growth velocity of body weight was 951±371 g at 1 month,824±278 g at 2 months and 749±219 g at 3 months,which showed a downward trend month by month;the growth velocity of head circumference was 1.5±0.7 cm at 1 month,1.4±0.5 cm at 2 months and 1.3±0.3 cm at 3 months,which showed a slow downward trend month by month.② No significant difference was found between formula powder group and breast feeding group in the growth velocity of height,body weight and circumference at 1,2 and 3 months respectively.The growth velocity of height,body weight and circumference in formula powder group also showed a downward trend month by month.③There was significant difference in both defecation frequency and stool character at enrolment,1,2 and 3 months between formula powder group and breast feeding group.④None of adverse events was considered directly attributable to formula powder or breast feeding in totally 224 infants during the study period.Conclusion The growth velocity of height,body weight and head circumference under breast feeding for 3 months of Chinese healthy breast feeding infants aged 1~2 months showed a downward trend month by month.The downward change month by month of growth velocity in head circumference was slower than that of height and body weight.The growth velocity trend in formula powder feeding infants was similar to that in breast feeding infants.