RESIDUAL DISEASE DETECTION IN ALL USING FLOW CYTOMETRY

使用流式细胞术检测所有残留疾病

• 批准号: 6710625
• 负责人: MICHAEL J BOROWITZ
• 金额: $ 18.07万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6710625
• 关键词: acute lymphocytic leukemia; child (0-11); clinical research; diagnosis design /evaluation; flow cytometry; human subject; minimal residual disease; neoplasm /cancer diagnosis; neoplasm /cancer relapse /recurrence; pediatric neoplasm /cancer

DESCRIPTION: (Adapted from the investigator's abstract) Although the cure rate of childhood ALL is among the highest of any cancers, there is still significant room for improvement both because some children still succumb to their disease and because others may obtain more treatment than is necessary for cure. Almost all children enter remission following initial therapy, but may patients harbor residual disease below the level that can be detected by conventional measurements. There is a growing body of evidence that presence of this minimal residual disease (MRD) may be an adverse prognostic factor. This project is designed to study children with ALL who are enrolled on front-line clinical trials of the Pediatric Oncology Group for newly diagnosed leukemia. The current study will employ a highly sensitive four color flow cytometric technique to study MRD and will answer the following questions: 1) What is the frequency with which children with ALL have phenotypically abnormal cells in the bone marrow or blood following induction therapy, or at the end of consolidation therapy, and what is the quantitative residual disease burden in such patients? 2) How dose the presence of MRD correlate with traditional risk factors? 3) Do patients with MRD have an increased risk of relapse and what quantitative level of positivity is optimal for distinguishing between higher and lower risk patients? 4) Do children with ALL who harbor MRD and receive more intensive therapy have a better outcome than those who do not receive this extra therapy? In preliminary experiments, he has found that he can detect residual leukemic blasts in the blood or marrow of some patients at the end of induction therapy. The range of postivity he has detected so far is from 0.33 percent to as low as .0054 percent of total cells. The studies described here will be closely integrated with other studies proposed in a companion grant as part of this IRPG. These other proposed studies will use molecular techniques to detect residual disease on the same samples tested here. Another goal of their study therefore is to compare flow and molecular technologies and determine the most sensitive, most predictive, and most cost-effective technical approach for the detection of clinically significant residual leukemic burden.

描述：（根据调查人员的摘要改编），尽管治愈率 童年时代全部是任何癌症中最高的 重大改进的空间，因为有些孩子仍然屈服于 他们的疾病，因为其他人可能获得的治疗比必要的更多 治愈。初次治疗后，几乎所有儿童都进入缓解，但是 可能患者将残留疾病置于可以检测到的水平以下 常规测量。越来越多的证据表明 这种最小的残留疾病（MRD）可能是预后不良因素。这 项目旨在研究所有参加前线的孩子 新诊断的白血病小儿肿瘤学组的临床试验。 当前的研究将采用高度敏感的四颜色流式细胞仪 研究MRD的技术，并将回答以下问题：1） 频率均在其表型中具有表型异常细胞的频率 诱导治疗后的骨髓或血液，或者在 合并疗法，以及什么是定量残留疾病负担 这样的患者？ 2）MRD的存在与传统风险的剂量如何 因素？ 3）MRD患者的复发风险增加吗？ 定量阳性水平是区分较高的阳性水平 和降低风险患者？ 4）与所有藏有MRD并接受的孩子一起 比没有收到此的人更强化的疗法的结果更好 额外的治疗？在初步实验中，他发现他可以检测到 在某些患者的血液或骨髓中的残留白血病爆炸 诱导疗法。到目前为止，他发现的后期范围来自0.33 百分比高达总细胞的0.0054％。这里描述的研究 将与同伴赠款中提出的其他研究紧密整合为 此IRPG的一部分。这些其他提出的研究将使用分子技术 在此处测试的相同样品上检测残留疾病。另一个目标 因此，他们的研究是比较流量和分子技术和 确定最敏感，最预测和最具成本效益的 检测临床上显着残留的技术方法 白血病负担。