年长儿童急性淋巴细胞白血病多中心疗效分析

Analysis of multicenter efficacy of acute lymphoblastic leukemia in older children

目的多中心研究年长儿童急性淋巴细胞白血病（ALL）的临床特征，评价多中心协作组方案（ALL一2005）的远期疗效。方法收集5家医院采用ALL-2005方案治疗的103例10～18岁初发ALL患儿资料，分析其临床特征、诱导缓解情况、远期疗效以及预后影响因素。结果①103例ALL患儿中男62例，女41例，起病时中位年龄12．3（10．3～17．4）岁。B—ALL90例（87．4％），T—ALL13例（12．6％）。中危组65例（63．1％），高危组38例（36．9％）。初诊时有4例（3．9％）患儿发生中枢神经系统白血病。89例行染色体核型检查的患儿中58例（65．2％）获得检测结果，其中正常核型37例（63．8％），异常核型21例（36．2％）。81例行分子生物学检查的患儿中16例（19．8％）融合基因检测阳性。②103例患儿经诱导治疗后97例（94．2％）获得缓解；28例复发，中位复发时间11．9（2．9～57．8）个月；38例（36．9％）死亡。截止2012年9月30日，中位随访47．0（0．4～92．6）个月，5年无事件生存（EFS）率与5年总生存率分别为（60．2±4．8）％和（64．1±4．7）％；中、高危患儿的5年EFS率分别为（73．8±5．5）％和（31．6±8-3）％，5年总生存率分别为（78．5±5．1）％和（35．9＋8．0）％（P〈0．01）。③预后影响因素分析结果显示，年龄14～18岁、BCR—ABL融合基因阳性或染色体存在t（9；22）是影响5年EFS的危险因素。结论年长儿童ALL发病和预后与其特殊的年龄、危险程度和生物学特性相关。BCR—ABL融合基因阳性或染色体存在t（9；22）是影响患儿预后的高危因素。ALL-2005治疗方案适用于大年龄组儿童ALL的治疗。

Objective To retrospectively analyze the clinical characteristics and the treatment outcomes of older children with acute lymphoblastic leukemia （ALL）, and to evaluate the multicenter cooperation regimen （ALL-2005）. Methods The clinical data of 103 newly diagnosed ALL children aged 10 to 18 years old from five hospitals were enrolled in this study. They were all received ALL-2005 protocol. The clinical characteristics, the event-free survival （EFS）, the overall survival （OS） and the prognostic analysis were evaluated. Results ① Of the103 patients, 62 were boys and 41 girls, with a median age of 12.3 years old. According to immunophenotyping, 90 （87.4%） of 103 patients were diagnosed as B-ALL and 13 （ 12.6% ） as T-ALL. According to risk factor, 65 （63.1% ） were in intermediate risk group （MR-ALL） and 38 （36.9%） in high risk group （HR-ALL）. Central nervous system leukemia （CNSL） happened in 4 （3.9%） patients at diagnosis. Of the 89 patients received chromosome test, 58 （65.2%） obtained the test results, including 21 （36.2%） with aberrational chromosomes and 37 （63.8%） with normal karyotype. Of 81 patients received molecular biological test, 16 （19.8%） were positive for fusion gene. ②After induction therapy, 97 （94.2%） obtained complete remission （CR）. Twenty-eight patients relapsed with a median time of 11.9 months （ranged 2.9-57.8 months）, and 38 （36.9%） patients died during the treatment. As of September 30, 2012, the median follow-up was 47 months （ranged 0.4 - 92.6 months）. The 5-year EFS and 5-year OS of ALL patients were （60.2±4.8）% and （64.1±4.7）%. The 5- year EFS of MR-ALL and HR-ALL were （73.8±5.5）% and （31.6±8.3 ）% （P〈0.01）, the 5-year OS of MR- ALL and HR-ALL were （78.5±5.1）% and （35.9±8.0）%（P〈0.01）, respectively. ③ Cox proportion hazard regression model analysis indicated that age of 14 - 18 years old and BCR-ABL translocation or t（9;22） were independent risk prognostic factor for 5-year EFS. Conclusion The incidence and prognosis in older childhood ALL were related with age, risk and biological characteristics. BCR-ABL translocation or t （9;22） was the risk factor of prognosis. ALL-2005 protocol was recommended as the regimen for older childhood ALL.