儿童急性淋巴细胞白血病2005方案多中心远期临床报告

Long-term results of multicenter study based on childhood acute lymphoblastic leukemia 2005protocol

目的通过多中心研究评价上海儿童医学中心急性淋巴细胞白血病2005（SCMC-ALL-2005）方案治疗儿童急性淋巴细胞白血病（ALL）的远期疗效及预后相关因素。方法统一采用SCMC-ALL-2005方案对2005年5月1日至2014年12月31日就诊于SCMC-ALL-2005多中心研究协作组共5家医院的1 497例初诊ALL患儿根据危险度分组进行分层治疗。危险度分组及对应的治疗强度以临床和生物信息、早期治疗反应、微量残留白血病（MRD）结果为依据。总体生存率（OS）和无事件生存率（EFS）分析采用Kaplan-Meier生存分析法，多因素分析采用COX回归多因素模型分析。结果随访至2016年12月31日，中位随访时间69（24-141）个月。5年、10年OS为（80.0±1.0）%和（76.0±2.0）%，5年、10年EFS为（69.0±1.0）%和（66.0±2.0）%，5年、10年复发率为（23.0±1.0）%和（25.0±2.0）%。其中低危组、中危组、高危组5年OS和EFS分别为：（91.1±1.4）%和（83.3±1.8）%、（79.2±1.5）%和（68.9±1.7）%、（52.9±4.4）%和（30.0±3.8）%。诱导治疗第55天792例患儿（82.8%）MRD〈0.01%，第55天MRD未转阴的患儿预后差（OR=1.9, 95%CI：1.3-2.7, P=0.001）。高危组中24例接受异基因造血干细胞移植，其中17例（70.8%）无病存活。本组患儿164例次发生了严重不良反应，46例死亡，治疗相关病死率为3.1%。结论多中心大样本研究证明SCMC-ALL-2005方案治疗儿童ALL疗效满意，有助于儿童白血病规范化治疗向全国推广。诱导第55天MRD结果与预后相关。

ObjectiveTo evaluate the long-term efficacy and prognostic factors of childhood acute lymphoblastic leukemia （ALL） enrolled in Shanghai Children＇s Medical Center-Acute Lymphoblastic Leukemia-2005（SCMC-ALL-2005） multicenter study.MethodsBetween May 2005 and December 2014, 1 497 newly diagnosed ALL patients were enrolled and treated in 5 hospitals of SCMC-ALL-2005 study group, using risk-stratified SCMC-ALL-2005 protocol. Risk group classification and treatment intensity were based on clinical features, genetic abnormalities, early response to treatment and levels of minimal residual disease （MRD）. Kaplan-Meier method was used to generate overall survival （OS） and event-free survival（EFS） curves. Cox proportional hazards models were used for multivariate analyses.ResultsThe patients were followed up to December 31, 2016, the median follow-up time was 69 months （24-141 months）. The 5-year and 10-year OS rates were （80.0±1.0）% and （76.0±2.0）%. The 5-year and 10-year EFS rates were （69.0±1.0）% and （66.0±2.0）%. The 5-year and 10-year relapse rates were （23.0±1.0）% and （25.0±2.0）%. The 5-year OS and EFS for low risk （LR）, intermediate risk （IR） and high risk （HR） were （91.1±1.4）% and （83.3±1.8）%, （79.2±1.5）% and （68.9±1.7）%, （52.9±4.4）% and （30.0±3.8）%, respectively. MRD negative status （〈0.01%） on day 55 was seen in 792 patients （82.8%） and positive MRD on day 55 was associated with poor prognosis （OR=1.9, 95%CI： 1.3-2.7, P=0.001）. Twenty-four HR patients received allogeneic hematopoietic stem cell transplantation and 17（70.8%） of them were alive and in remission. A total of 164 severe adverse events occurred, 46 of them died, treatment-related mortality was 3.1%.ConclusionsIn this large sample research, the overall outcome for multi-center SCMC-ALL-2005 study was favorable. This helps to promote the standardized treatment of childhood ALL to the whole country. MRD results on day 55 of induction therapy have important prognostic and therapeutic implications.