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In vitro chemosensitivity by MTT assay and clinical outcomes in childhood leukemia

MTT 测定的体外化疗敏感性和儿童白血病的临床结果

基本信息

批准号：
05670667
负责人：
HONGO Teruaki
金额：
$ 1.34万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670667/
关键词：
MTT assay Childhood leukemia Chemosensitivity Ph1 positive ALL Infantile leukemia Anticancer drug T-ALL Mixed lineage ALL MTT アッセイ Ph1 positive ALL Mixed lineage ALL MTT assay G-CSF receptor childhood ALL anticamcer drug LD70

项目摘要

We investigated the relationship between in vitro sensitivity and clinical outcomes in 196 children with newly diagnosed ALL.We explored whether the sensitivity to a combination of four drugs DPAV (Dex, Pred, Asp, VCR) predicted induction failure and early relapse (IF/e.rel). [Patients and Methods] Eligible were children (age 0-16 years) with non-B cell ALL,newly diagnosed between 1989 and 1995. BM samples were sent for in vitro drug tests. There were 142 samples of common ALL (cALL), 21 of T-ALL,28 of mixed lineage ALL (mix ALL) and 5 of undifferentiated ALL (uALL). All patients (pts) were treated with the ALL protocol of Pred, Asp and VCR for standard risk, plus CPA and DNR for high risk, as induction therapy. In vitro tests were carried out with a four-day culture and MTT assay. We tested 16 drugs and calculated LD70 for 14 drugs, and LCS for Dex and Pred.For each single drug, pts were classified into two groups, as either S (lower than median LD70 or LCS) or R (higher than median L … More D70 or LCS).[Statistics] The Kaplan-Meier method for EFS,log rank test, Fisher's PLSD,and contingency table analysis for multi-variate comparison were conducted using Stat View-J4.5 (Abacus Concepts).[Results] EFS (3 yrs) of pts with cALL,T-ALL,mix ALL,uALL were 0.727,0.560,0.534,0.600 respectively. S group pts for Pred, VP16, VCR and MIT had superior EFS to R group pts (p<0.05). When we classified pts into three groups (S,I,R) by sensitivity to four drugs (DPAV), EFS (3 yrs) of S group (n=41) was 0.833, that of I (n=78) was 0.752, and that of R (n=74) was 0.546 (p=0.0011). Then we investigated whether the drug sensitivity of S or R was related to three prognostic groups (CCR,IF/e.rel, late relapse). S groups of Pred, BLM,VP16, VCR,MIT were significantly related to CCR,and R to IF/e.rel (p<0.05). When we used S,I and R for DPAV sensitivity, S and I pts tended to maintain CCR,and R pts tended to undergo IF/e. rel and late relapse (p=0.004). [Conclusion] In vitro drug sensitivity testing together with immunological marker testing provides prognostic information for childhood ALL. Less

我们调查了196例初诊ALL患儿的体外敏感性与临床结局的关系，探讨了对DPAV（Dex、Pred、Asp、VCR）四种药物联合用药的敏感性是否预示诱导失败和早期复发（IF/e.rel）。[患者和方法]入选对象为1989年至1995年间新诊断的非B细胞ALL儿童（年龄0-16岁）。将BM样品送去进行体外药物试验。其中普通型ALL（cALL）142例，T-ALL 21例，混合型ALL（mixALL）28例，未分化型ALL（uALL）5例。所有患者（pts）均接受Pred、Asp和VCR（标准风险）+CPA和DNR（高风险）的ALL方案作为诱导治疗。体外实验采用4天培养和MTT法。我们测试了16种药物，并计算了14种药物的LD 70和Dex和Pred的LCS，对于每种单一药物，将患者分为两组，S组（低于LD 70或LCS中位数）或R组（高于LD 70或LCS中位数）。 ...更多信息 D 70或LCS）。[统计学]采用统计学软件Stat View-J 4.5（Abacus Concepts）进行EFS的Kaplan-Meier法、对数秩检验、Fisher's PLSD和多变量比较的列联表分析。[结果] cALL、T-ALL、mixALL、uALL患者3年生存率分别为0.727、0.560、0.534、0.600。S组患者的Pred、VP 16、VCR和MIT的EFS上级R组患者（p<0.05）。根据对四种药物的敏感性（DPAV）将患者分为三组（S、I、R），S组（n=41）的EFS（3年）为0.833，I组（n=78）为0.752，R组（n=74）为0.546（p=0.0011）。然后，我们研究了S或R的药物敏感性是否与三个预后组（CCR，IF/e.rel，晚期复发）相关。S组的Pred、BLM、VP 16、VCR、MIT与CCR呈显著相关，R组与IF/e.rel呈显著相关（p<0.05）。当我们使用S、I和R作为DPAV敏感性时，S和I患者倾向于维持CCR，R患者倾向于发生IF/e。复发和晚期复发（p=0.004）。[结论]体外药敏试验结合免疫学标志物检测可为儿童ALL的预后提供参考。少