247例儿童急性淋巴细胞白血病长期随访及预后分析

发布时间：2019-04-08 19:39

【摘要】：目的：回顾性分析儿童急性淋巴细胞白血病(ALL)的治疗效果和影响预后因素。方法：对本院2005年1月11日-2008年10月30日期间收治的急性淋巴细胞白血病332例进行临床分析。其中247例患儿接受了有效治疗并纳入生存分析,85例因患儿因发生下述情况未纳入生存分析：1.确诊为新发ALL后未接受任何治疗或是化疗时间小于2周；2.化疗未开始时已死亡。治疗方案采用：诱导缓解采用VDLD,巩固治疗采用2周的CAT,预防髓外白血病采用3个疗程的大剂量甲氨蝶呤(HD-MTX),早期强化采用连续3个疗程每3天1次的VP16+Ara-C,维持阶段用VD(VCR+DXM)、6-TG+MTX、COAD(仅对高危组)门诊小化疗方案定期序贯治疗。门诊小化疗维持的同时采用VDLD和连续3个疗程每6个月1次的VP16+Ara-C再次强化。接着2个疗程的大剂量甲氨蝶呤(HD-MTX)预防髓外白血病直到HDMTX总次数达到9次(中低危组)或11次(高危组)。晚期强化和维持治疗至持续完全缓解(CCR)2.5年(中低危组女孩)、3年(高危组女孩)、3年(中低危组男孩)、3.5年(高危组男孩)停药。结果：在247例接受有效治疗的患儿中,235例经诱导后获得完全缓解(CR),CR率为95.1%。41例出现复发,其中38例仅有骨髓复发,1例出现脑白复发,2例出现睾白复发,1例同时出现骨髓和脑白复发,5年累计复发率16.6%,高危组比中低危组有显著高的复发率(28%和13.7%,P=0.015)。在染色体检查成功的85例患儿中,t(9；22)/Ph染色体、亚二倍体、超二倍体、阳性分别有10例、2例、10例。在218例进行融合基因检查的患儿中,TEL/AML1阳性、MLL基因重排、BCR/ABL阳性分别有28例、1例、10例,其余179例所有融合基因均为阴性。免疫分型显示Pro-B ALL7例(2.8%),c-ALL161例(65.2%),Pre-B ALL26例(10.5%),B-ALL3例(1.2%),T-ALL39例(15.8%),双表型4例(1.6%),未确定7例(2.8%)。用Kaplan-eier法对本组247例患儿进行生存分析显示：3年、5年和7年无事件生存率(EFS)分别为76.7±2.7%,75.4±2.8%和75.4±2.8%。低危组(n=167)、中危组(n=30)、高危组(n=50)的3年无事件生存率(EFS)分别为82.4±3.0%、66.7±8.6%、60.9±7.0%,5年EFS分别为81.0±3.]%、63.0±8.9%、60.9±7.0%,中危组、高危组的长期EFS明显低于低危组(P分别为0.028、0.004)。单因素分析显示：t(9；22)/Ph染色体/BCR/ABL阳性、亚二倍体、超二倍体、MLL基因重排、T-ALL、性别、表达如CD13和CD33等髓系标志均与长期EFS无明显关联。TEL/AML1阳性、15天时的诱导成功、28天时的诱导成功、良好的经济状况(有医保或户籍所在地为城市)、年龄1-10岁、初诊白细胞数100×109/L是ALL长期生存的预后良好因子(P分别为0.034、0.031、0.003、0.000、0.039、0.000)。Cox多因素回归分析显示：28天时的诱导成功(RR=1.743,P=0.035)和初诊白细胞数100×109/L(RR=2.5,P=0.001)是长期EFS的独立的预后良好因子。结论：本组低危、中危和高危儿童ALL病例的5年EFS为81.0±3.1%、63.0±8.9%、60.9±7.0%。TEL/AML1阳性、15天时的诱导成功、28天时的诱导成功、良好的经济状况、年龄1-10岁、初诊白细胞数100×109/L是ALL的预后良好因子,其中对于诱导缓解的反应和初诊白细胞数对于提示ALL的预后具有重要意义。
[Abstract]:Objective: To retrospectively analyze the therapeutic effect of childhood acute lymphoblastic leukemia (ALL) and the factors affecting the prognosis. Methods: The clinical score of 332 cases of acute lymphoblastic leukemia in our hospital from Jan.11,2005 to Oct.30,2008 A total of 247 children were treated with effective treatment and included in the survival analysis, and 85 were not included in the survival analysis due to the following: 1. No treatment or chemotherapy time is less than 2 weeks after the diagnosis of new ALL; 2. The chemotherapy was not started The treatment protocol adopted the following steps of: inducing and relieving the use of VLD, consolidating the treatment by 2 weeks of CAT, and preventing the myelogenous leukemia from adopting 3 courses of high-dose methotrexate (HD-MTX), and early strengthening the VP16 + Ara- C. The maintenance phase uses VD (VCR + DXM),6-TG + MTX and COAD (only for high-risk group) out-patient small-chemotherapy program to be treated regularly. P16 + Ara-C of 1 time every 6 months with VLD and 3 courses of treatment at the same time for the maintenance of small-dose chemotherapy in the clinic Treatment of extramedullary leukemia with high-dose methotrexate (HD-MTX) of 2 courses of treatment until the total number of HDMTX reaches 9 (low-risk group) or 11 (high-risk group) ). Late strengthening and maintenance of treatment to sustained complete response (CCR) 2.5 years (low-risk group girls),3 years (high-risk group girls),3 years (low-risk group boys) and 3.5 years (high-risk group boys) Results: Of the 247 children treated with effective treatment,235 patients had complete remission (CR) after induction, and the CR rate was 95.1%. At present,38 of them had bone marrow recurrence,1 case of cerebral white recurrence,2 cases of recurrent white recurrence,1 case of bone marrow and brain-white recurrence,5-year cumulative recurrence rate of 16.6%, high-risk group had a significantly higher recurrence rate (28% and 13.7%, P = 0.0). 15) Among the 85 children with successful chromosome examination, t (9;22)/ Ph chromosome, subdiploid, hyperdiploid and positive were 10 and 2, respectively. There were 28 cases of TEL/ AML1 positive, MLL gene rearrangement, BCR/ ABL positive,1 case,10 cases and all the other 179 cases of all the fusion genes. Negative. The immunophenotyping showed Pro-B ALL7 (2.8%), c-ALL161 (65.2%), Pre-B ALL26 (10.5%), B-AL3 (1.2%), T-ALL39 (15.8%), double-phenotype 4 (1.6%), and no 7 cases (2. The survival analysis of 247 children in this group showed that there were no event-free survival rates (EFS) of 76.7%, 75.4% and 75.4% in 3,5 and 7 years, respectively. The 3-year non-event-free survival rate (EFS) of low-risk group (n = 167), middle-risk group (n = 30) and high-risk group (n = 50) was 82.4%, 3.0%, 66.7% 8.6%, 60.9% and 7.0%, respectively. The long-term EFS of%, 63.0, 8.9%, 60.9-7.0%, medium-risk group and high-risk group was significantly lower than that of low-risk group (P = 0.028, 0.0, respectively). 04). The single factor analysis showed that t (9;22)/ Ph chromosome/ BCR/ ABL-positive, subdiploid, hyperdiploid, MLL gene rearrangement, T-ALL, sex, expression such as CD13 and CD33 myeloid markers were all related to long-term EFS Significant association. The induction of TEL/ AML1 was successful at 15 days, the induction of 28 days was successful, the good economic condition (with medical insurance or the place of household registration as the city), the age of 1-10 years, the number of white blood cells 100-109/ L was the good prognostic factor for ALL long-term survival (P = 0.034, 0.031, 0.003, 0.000, 0.039, 0.0, respectively). 00). Cox's multi-factor regression analysis showed that the induction was successful at 28 days (RR = 1.743, P = 0.035) and the initial number of leukocytes 100-109/ L (RR = 2.5, P = 0.001) was an independent prognostic factor for long-term EFS. The results showed that the 5-year EFS was 81.0-3.1%, 63.0-8.9%, 60.9-7.0%, TEL/ AML1-positive and 15-day induction. The following good factors, in which the response to the induction response and the number of initial white blood cells are useful for the prognosis of the ALL
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R733.71

【相似文献】