【摘要】 目的探讨多中心合作开展小儿急性淋巴细胞白血病(ALL)化疗的可能性和提高ALL治愈率的新策略。方法协作组由广州市7家大型医院组成,各单位指定负责人1人,并设立专职资料管理员1人。协作组邀请香港中文大学威尔斯亲王医院为顾问单位。各单位对符合入选标准的新诊断标准危险型(SR)和中度危险型(IR)ALL患儿均采用GZ-2002 ALL化疗方案,所有病例按细胞形态学、免疫学和细胞遗传学分型。根据发病时的年龄、外周血白细胞、第8天的泼尼松反应、t(9:22)或t(4;11)、BCR/ABL和MLL/AF4融合基因,以及化疗第33天是否完全缓解确定临床类型。GZ-2002方案以BFM2002方案为基础,总疗程共104周,由诱导期、巩固期、再诱导期和维持期组成。结果 2002年10月~2009年6月,协作组共收治ALL患儿617例,随访至2009年10月31日,中位随访时间44.5个月(范围:4~84个月)。按协作组诊断标准,把儿童ALL分为SR、IR和高危型(HR)。入组采用GZ-2002 ALL化疗方案的SR和IR患儿共446例,男227例,女169例;年龄1~14岁(中位年龄6岁)。诱导期的总完全缓解率为99.8%(445/446)。SR组3年和5年无事件生存率(EFS)分别为(90.5±5.0)%和(82.0±4.0)%。IR组3年和5年EFS分别为(88.0±6.0)%和(78.0±5.0)%,两组差异均有显著性意义(P<0.05)。至随访终止日,共随访到回复病例413例,占总例数的92.6%。可随访例数中无事件生存者339例(82.1%),其中停药无病生存者267例(78.8%),进入维持阶段72例(21.2%)。有"事件"者78例(18.9%),其中复发47例(11.4%),非复发死亡20例(4.8%)。远期毒副作用8例(1.9%),第2肿瘤3例(0.7%);复发者已死亡24例(含6例复发后放弃),带病存活23例。死亡的中位时间为治疗后7.9个月(1.5~23个月)。失访33例,其中停药后失访5例,维持期间因出国、搬家、原联络地址变更和回原籍(广东省以外)等共28例。结论 GZ-2002 ALL化疗方案的疗效满意,广州地区多中心协作的模式是成功的,这种协作模式对推动我国开展更大规模的协作提供了宝贵的经验。更多还原

【Abstract】 Objective To investigate the possibility of multiple-center cooperation on chemotherapy for childhood leukemia,and explore new strategies of enhancing the cure rate of childhood leukemia in Guangzhou,China.Methods Seven main hospitals in Guangzhou attended in our study group,and the Wales Hospital of HongKong Chinese University attended as a consultant.One person was appointed to be in charge of the therapeutic work in each hospital,and another full-time administrator took charge of all the records.All the patients enrolled in the standard risk(SR) group or interim risk(IR) group according to the diagnosis standards were treated with GZ-2002 ALL protocol.The material records were sorted out and analyzed.A discussion meeting was held among our members of the group twice a year.Results Six hundred and seventeen cases were initially enrolled in the seven hospitals from Oct.of 2002 to June of 2009.The children were diagnosed as ALL according to the GZ-2002ALL chemotherapy regimen.All cases were classified into SR,IR,and HR regarding cytomorphology(M),immunology(I),and cytogenetics(C) and response to the first chemotherapy.A total of 446 patients were included in the research and treated with the GZ-BFM2002ALL chemotherapy regimen.They consisted of 227 males and 169 females,ranging in age from one to 14 years,with an average of 6 years.The GZ-2002ALL chemotherapy regimen was established based on the ALLIC-BFM2002 regimen.The regimen lasted for 104 weeks,consisting of induction,consolidation,re-induction and maintenance.The total complete remission rate in induction of SR or IR was 99.8%(445/446).The 3-year EFS was(90.5±5.0)% and the 5-year EFS was(82.0±4.0)% in the SR group,while they were respectively(88.0±6.0)% and(78.0±5.0)% in the IR group.There was a statistically significant difference between groups by Log-rank test(P<0.05).Four hundred and thirteen ALL children were followed up,accounting for 92.6% of all.There were 339(82.1%) cases with EFS,consisting of 267(78.8%) cases with DFS and 72(21.2%) cases in the maintenance period.Seventy-eight cases of events were observed,including 47(11.4%) cases of recurrence,20(4.8%) cases of non-recurrent death,8(1.9%) cases of long-term toxicities,and 3(0.7%) cases of new tumors.Among the recurrent cases,there were 24 deaths(including 6 cases of treatment discontinuation following recurrence) and 23 survival cases with disease.The median time to death was 7.9 months(range from 1.5~23 months).Five of them were missing following drug discontinuation,and 28 were missing due to going abroad,home relocation,address change,and migration to other provinces.Conclusion The therapeutic efficacy of GZ-2002 ALL protocol for childhood leukemia chemotherapy is approving,and the mode of multiple-center investigation is demonstrated successful.All these will contribute to conducting extensive cooperation of work groups in China.更多还原