【摘要】：目的：回顧性分析兒童急性淋巴細(xì)胞白血病(ALL)的治療效果和影響預(yù)后因素。 方法：對本院2005年1月11日-2008年10月30日期間收治的急性淋巴細(xì)胞白血病332例進(jìn)行臨床分析。其中247例患兒接受了有效治療并納入生存分析,85例因患兒因發(fā)生下述情況未納入生存分析：1.確診為新發(fā)ALL后未接受任何治療或是化療時間小于2周；2.化療未開始時已死亡。治療方案采用：誘導(dǎo)緩解采用VDLD,鞏固治療采用2周的CAT,預(yù)防髓外白血病采用3個療程的大劑量甲氨蝶呤(HD-MTX),早期強化采用連續(xù)3個療程每3天1次的VP16+Ara-C,維持階段用VD(VCR+DXM)、6-TG+MTX、COAD(僅對高危組)門診小化療方案定期序貫治療。門診小化療維持的同時采用VDLD和連續(xù)3個療程每6個月1次的VP16+Ara-C再次強化。接著2個療程的大劑量甲氨蝶呤(HD-MTX)預(yù)防髓外白血病直到HDMTX總次數(shù)達(dá)到9次(中低危組)或11次(高危組)。晚期強化和維持治療至持續(xù)完全緩解(CCR)2.5年(中低危組女孩)、3年(高危組女孩)、3年(中低危組男孩)、3.5年(高危組男孩)停藥。 結(jié)果：在247例接受有效治療的患兒中,235例經(jīng)誘導(dǎo)后獲得完全緩解(CR),CR率為95.1%。41例出現(xiàn)復(fù)發(fā),其中38例僅有骨髓復(fù)發(fā),1例出現(xiàn)腦白復(fù)發(fā),2例出現(xiàn)睪白復(fù)發(fā),1例同時出現(xiàn)骨髓和腦白復(fù)發(fā),5年累計復(fù)發(fā)率16.6%,高危組比中低危組有顯著高的復(fù)發(fā)率(28%和13.7%,P=0.015)。在染色體檢查成功的85例患兒中,t(9；22)/Ph染色體、亞二倍體、超二倍體、陽性分別有10例、2例、10例。在218例進(jìn)行融合基因檢查的患兒中,TEL/AML1陽性、MLL基因重排、BCR/ABL陽性分別有28例、1例、10例,其余179例所有融合基因均為陰性。免疫分型顯示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%),雙表型4例(1.6%),未確定7例(2.8%)。用Kaplan-eier法對本組247例患兒進(jìn)行生存分析顯示：3年、5年和7年無事件生存率(EFS)分別為76.7±2.7%,75.4±2.8%和75.4±2.8%。低危組(n=167)、中危組(n=30)、高危組(n=50)的3年無事件生存率(EFS)分別為82.4±3.0%、66.7±8.6%、60.9±7.0%,5年EFS分別為81.0±3.]%、63.0±8.9%、60.9±7.0%,中危組、高危組的長期EFS明顯低于低危組(P分別為0.028、0.004)。單因素分析顯示：t(9；22)/Ph染色體/BCR/ABL陽性、亞二倍體、超二倍體、MLL基因重排、T-ALL、性別、表達(dá)如CD13和CD33等髓系標(biāo)志均與長期EFS無明顯關(guān)聯(lián)。TEL/AML1陽性、15天時的誘導(dǎo)成功、28天時的誘導(dǎo)成功、良好的經(jīng)濟狀況(有醫(yī)保或戶籍所在地為城市)、年齡1-10歲、初診白細(xì)胞數(shù)100×109/L是ALL長期生存的預(yù)后良好因子(P分別為0.034、0.031、0.003、0.000、0.039、0.000)。Cox多因素回歸分析顯示：28天時的誘導(dǎo)成功(RR=1.743,P=0.035)和初診白細(xì)胞數(shù)100×109/L(RR=2.5,P=0.001)是長期EFS的獨立的預(yù)后良好因子。 結(jié)論：本組低危、中危和高危兒童ALL病例的5年EFS為81.0±3.1%、63.0±8.9%、60.9±7.0%。TEL/AML1陽性、15天時的誘導(dǎo)成功、28天時的誘導(dǎo)成功、良好的經(jīng)濟狀況、年齡1-10歲、初診白細(xì)胞數(shù)100×109/L是ALL的預(yù)后良好因子,其中對于誘導(dǎo)緩解的反應(yīng)和初診白細(xì)胞數(shù)對于提示ALL的預(yù)后具有重要意義。
[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
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2013
【分類號】：R733.71

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