论文部分内容阅读
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。
Objective To investigate the possibility of multicentre cooperation in the treatment of pediatric acute lymphoblastic leukemia (ALL) and to improve the cure rate of ALL. Methods Collaborative Group consists of 7 large hospitals in Guangzhou City, each unit designated person in charge and the establishment of a full-time data administrator 1. The collaborative group invited the Prince of Wales Hospital of The Chinese University of Hong Kong as a consultant unit. GZ-2002 ALL chemotherapy was used in all children with newly diagnosed criteria of risk (SR) and moderate-risk (ALL) ALL who met the inclusion criteria. All cases were classified by cell morphology, immunology and cytogenetics. According to the age of onset, peripheral blood leucocytes, prednisone reaction on day 8, t (9:22) or t (4; 11), BCR / ABL and MLL / AF4 fusion genes, and on day 33 of chemotherapy Relieve to determine the clinical type. Based on the BFM2002 protocol, the GZ-2002 regimen is based on a total of 104 weeks of treatment consisting of induction, consolidation, reinduction and maintenance. Results From October 2002 to June 2009, 617 children with ALL were enrolled in the collaborative group. The follow-up was October 31, 2009 and the median follow-up time was 44.5 months (range, 4 to 84 months). By collaborative group diagnostic criteria, the children ALL divided into SR, IR and high-risk type (HR). A total of 446 SR and IR children enrolled in the GZ-2002 ALL regimen included 227 males and 169 females, aged 1 to 14 years (median age, 6 years). The total induction of complete remission was 99.8% (445/446). The 3-year and 5-year event-free survival rates (EFS) in SR group were (90.5 ± 5.0)% and (82.0 ± 4.0)%, respectively. The 3-year and 5-year EFS of IR group were (88.0 ± 6.0)% and (78.0 ± 5.0)%, respectively, with significant difference between the two groups (P <0.05). To the end of follow-up, a total of 413 cases were followed up, accounting for 92.6% of the total cases. There were 339 cases (82.1%) with no event survivors in the follow-up cases, including 267 cases (78.8%) with disease-free survivors and 72 cases (21.2%) in the maintenance phase. There were 78 cases (18.9%) with “incident”, of which 47 cases (11.4%) were relapse and 20 cases (4.8%) were non-recurrence. Long-term toxic side effects in 8 cases (1.9%), the second tumor in 3 cases (0.7%); recurrence has died in 24 cases (including 6 cases relapse after giving up), 23 cases with disease survived. The median time to death was 7.9 months (1.5-23 months) after treatment. Among them, 33 were lost to follow-up, of which 5 were lost to treatment after discontinuation of treatment. A total of 28 cases were lost because of going abroad, moving home, changing the original contact address and returning to their hometowns (other than Guangdong Province). Conclusions The curative effect of GZ-2002 ALL chemotherapy is satisfactory. The model of multi-center collaboration in Guangzhou is successful. This collaborative model provides valuable experience for promoting the large-scale collaboration in our country.