OUTCOME PREDICTION IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA BY MOLECULAR QUANTIFICATION OF RESIDUAL DISEASE AT THE END OF INDUCTION
OUTCOME PREDICTION IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA BY MOLECULAR QUANTIFICATION OF RESIDUAL DISEASE AT THE END OF INDUCTION
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DOI：
10.1016/s0140-6736(94)90988-1
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发表时间：
1994-01-22
期刊：
影响因子：
168.9
通讯作者：
MORLEY, AA
中科院分区：
文献类型：
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作者：
BRISCO, MJ;CONDON, J;MORLEY, AA
检测和量化急性淋巴细胞白血病（ALL）化疗后微小残留病（MRD）的方法可以通过识别需要或多或少强化治疗的患者来改善治疗。我们使用克隆特异性聚合酶链反应检测白血病克隆中重排的免疫球蛋白重链基因，并通过有限稀释分析对该克隆进行定量。通过从181名ALL儿童中提取DNA，成功地对MRD进行了定量，这些儿童在就诊时总白细胞计数低于100 × 10（9）/L，并参加了两项临床试验，在1980- 1984年和1985- 1989年，在38名患者的首次缓解骨髓中检测到白血病，数量在6.7 × 10（2）和9.9 × 10（-7）细胞之间;这些患者中有26人复发。尽管研究了522-496 000个基因组，但在50名未检测到MRD的患者中，只有6名复发。在每项试验中，MRD检测和结局之间的相关性对患者来说都是显著的。在第一个试验中，患者在检测到的所有MRD水平下复发，而在后一个试验中，治疗更密集，结果更好，MRD的程度与复发的可能性密切相关（5/5例患者MRD>10（-3），4/10例患者MRD为10（-3）至2 x 10（-5），0/3例患者MRD水平低于2 x 10（-5），26例中2例未检测到MRD）。化疗后白血病细胞的早期定量可能是预测儿童ALL结局并因此进行个体化治疗的成功策略，因为结果表明白血病的体内药物敏感性和诱导后治疗仍待杀死的白血病细胞的数量。
Methods to detect and quantify minimal residual disease (MRD) after chemotherapy for acute lymphoblastic leukaemic (ALL) could improve treatment by identifying patients who need more or less intensive therapy. We have used a clone-specific polymerase chain reaction to detect rearranged immunoglobulin heavy-chain gene from the leukaemic clone, and quantified the clone by limiting dilution analysis.MRD was successfully quantified, by extracting DNA from marrow slides, from 88 of 181 children with ALL, who had total leucocyte counts below 100 x 10(9)/L at presentation and were enrolled in two clinical trials, in 1980-84 and 1985-89, Leukaemia was detected in the first remission marrow of 38 patients, in amounts between 6.7 x 10(2) and 9.9 x 10(-7) cells; 26 of these patients relapsed. Of 50 patients with no MRD detected, despite study of 522-496 000 genomes, only 6 relapsed. The association between MRD detection and outcome was significant for patients in each trial. In the first trial, patients relapsed at all levels of detected MRD, whereas in the later trial, in which treatment was more intensive and results were better, the extent of MRD was closely related to the probability of relapse (5 of 5 patients with >10(-3) MRD, 4 of 10 with 10(-3)to 2 x 10(-5), 0 of 3 with levels below 2 x 10(-5), and 2 of 26 with no MRD detected).Early quantification of leukaemic cells after chemotherapy may be a successful strategy for predicting outcome and hence individualising treatment in childhood ALL, because the results indicate both in-vivo drug sensitivity of the leukaemia and the number of leukaemic cells that remain to be killed by post-induction therapy.