儿童多脏器受累朗格汉斯细胞组织细胞增生症131例临床研究

Clinical study of 131 children with multi-system Langerhans cell histiocytosis

目的分析多脏器受累的朗格汉斯细胞组织细胞增生症（MS—LCH）患儿的临床特点、治疗反应及预后相关因素。方法收集上海儿童医学中心血液肿瘤科2007年1月至2013年12月收治的131例MS—LCH患儿的病例资料。所有病例均采用上海儿童医学中心LCH方案（LCH-Ⅱ改良方案）化疗，采用Kaplan．Meier方法计算其总体生存率（0S）及无事件生存率（EFS），患儿组间EFS及0S差异行LogRank检验，多因素Cox回归分析其预后相关因素。结果131例患儿中男86例，女45例；中位发病年龄3岁（3个月-14岁）。6周诱导治疗后评估总有效率（完全缓解±好转）为79％（104／131），有危险器官受累者6周治疗后有效率为74％（48／65）。131例患儿3年EFS为（62±5）％，3年0s为（82±4）％。起病时年龄≤2岁、危险器官受累及6周治疗无效是影响LCH预后的重要因素，三组间3年os差异均有统计学意义（x^2=12．600、11．583、38．711，P=0．000、0．001、0．000）。对上述因素进一步采用多因素分析：危险器官受累及诱导治疗6周无效是影响MS—LCH患儿生存率的最主要因素（OR：12．352、14．356，P=0．001、0．000），起病时年龄≤2岁不是独立的危险因子（OR=1．013，P=0．207）。131例患儿复发或进展率28％（36／131），中位复发或进展时间为11（1—25）个月，其中有危险器官复发或进展者预后差，3年OS仅为（18±3）％。危险器官受累、6周诱导治疗无效者及较小年龄患儿更易发生病情进展或复发，差异均有统计学意义（x^2=15．747、7．289，Z=3．865；P=0．000、0．007、0．000）。结论危险器官受累及诱导治疗6周疗效不佳是影响MS-LCH患儿预后的最重要因素。再次诱导治疗可提高此部分患儿的生存率，有效的挽救方案是提高复发或进展患儿生存率的关键。

Objective To analyze the clinical characteristics and treatment outcome of children with multi-system Langerhans cell histioeytosis （MS-LCH）. Method From January 2007 to December 2013, newly diagnosed patients with histopathologically-confirmed MS-LCH were enrolled in this retrospective study. All patients were treated on the Shanghai Children＇s Medical Center LCH protocol （ LCH- 11 modified protocol）. Survival was determined using the Kaplan-Meier method with differences between different groups compared using the Log-Rank test. Prognostic relevance of different parameters were analyzed by Cox proportional hazard model. Result Of the 131 patients （86 boys and 45 girls）, the median age was 3 years （range 3 months to 14 years）. Rapid response at week 6 was achieved in 79% （104/131） evaluable patients and 74% patients （48/65） with risk organ involvement. The 3-year event free survival （EFS） and 3-year overall survival （OS） for all cases were （62 ± 5 ） % and （ 82 ± 4 ） %. The 3-year OS was significantly different between age at diagnosis ≤ 2 years and 〉 2 years group. The 3-year OS was also significantly different between patients with and without risk organ involvement. The 3-year OS of patients who had rapid response at week 6 was significantly higher than that of those without rapid response （ X^2 = 12. 600,11. 583, 38. 711 ;P =0. 000,0. 001,0. 000）. Cox regression analysis showed that risk organ involvement and poor response at week 6 were the most important prognostic factors for patients with MS-LCH （ OR = 12. 352,14. 356;P = 0. 001,0. 000）. However, age was not the independent prognostic risk factor （ OR = 1. 013,P = 0. 207）. There were 36 patients （28% , 36/131 ） who experienced disease progression or relapse. The time to disease progression or relapse ranged from 1 to 25 months from the initial diagnosis （median 11 months）. Significantly lower OS （18 ± 3 ）% was observed in 20 patients with risk organ involvement at progression or relapse. Patients with poor response at week 6, younger age or risk organ involvement at diagnosis was associated with disease progression/relapse （ X^2 = 15. 747, 7. 289 ,Z = 3. 865 ;P = 0. 000,0. 007, 0. 000）. Conclusion Risk organ involvement and poor response at week 6 are the strongest prognostic factors for patients with MS-LCH. Second initial treatment for patients with poor response at week 6 and effective salvage therapy need to be taken into account in our future studies.