DETECTION OF MDS USING FISH IN PRETRANSPLANT SAMPLES

使用移植前样本中的鱼检测 MDS

• 批准号: 6514402
• 负责人: DAVID D HURD
• 金额: $ 16.2万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6514402
• 关键词: acute myelogenous leukemia; autologous transplantation; chromosome aberrations; cryopreservation; diagnosis design /evaluation; fluorescent in situ hybridization; human subject; neoplasm /cancer diagnosis; patient oriented research; preneoplastic state; stem cell transplantation

DESCRIPTION: (Adapted from the investigator's abstract) Therapy associated myelodysplastic syndromes (tMDS) and acute myelogenous leukemia (tAML) have been seen with increasing frequency following high dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT). However, tMDS and tAML can also develop following the use of standard doses of chemotherapy and radiation for the treatment of patients for malignancy. Some investigators have hypothesized that the preparative regimen for transplant is the primary etiology for the post AHSCT tMDS/tAML. Other investigators have hypothesized that it is the exposure to the prior chemotherapy and/or radiation therapy that causes the cytogenetic abnormalities in the hematopoietic stem cells. These stem cells are then collected and stored and are given back to patients following the high dose therapy. While the tMDS/tAML is then expressed post AHSCT, the etiology is the prior treatment. Standard cytogenetic analysis of bone marrow samples prior to transplant has not proven to be sensitive enough to reliably detect which patients are at the highest risk for developing tMDS/tAML. However, in a pilot study using FISH, 9 of 12 patients who developed tMDS/tAML following AHSCT were found to have the same cytogenetic abnormality in the pre-transplant samples strongly suggesting that the latter hypothesis is correct. In none of the patients tested did standard cytogenetic analysis of metaphase karyotypes detect the cytogenetic abnormality. This proposal will expand the experience of using FISH to detect tMDS/tAML associated cytogenetic abnormalities to determine the sensitivity of this technique. If FISH can be shown to reliably predict which patients are at high risk for the development tMDS/tAML, these patients should be excluded from AHSCT and alternative treatment approaches could be applied.

描述：（改编自研究者的摘要）相关治疗 骨髓增生异常综合征 (tMDS) 和急性髓性白血病 (tAML) 在大剂量化疗后出现的频率越来越高 自体造血干细胞移植（AHSCT）。然而，tMDS 和 使用标准剂量的化疗后也可能出现 tAML 放射治疗恶性肿瘤患者。一些调查人员已经 假设移植的准备方案是主要的 AHSCT 后 tMDS/tAML 的病因学。其他研究人员假设 之前接受过化疗和/或放射治疗 导致造血干细胞的细胞遗传学异常。这些 然后收集并储存干细胞并回输给患者 大剂量治疗后。然后 tMDS/tAML 会在术后表达 AHSCT，病因是既往治疗。标准细胞遗传学分析 移植前的骨髓样本尚未被证明足够敏感 可靠地检测哪些患者的患病风险最高 tMDS/tAML。然而，在一项使用 FISH 的试点研究中，12 名患者中有 9 名出现了 AHSCT 后的 tMDS/tAML 被发现具有相同的细胞遗传学异常 在移植前样本中强烈表明后一种假设是 正确的。在所有接受测试的患者中，均未进行标准细胞遗传学分析 中期核型检测细胞遗传学异常。该提案将 扩展使用 FISH 检测 tMDS/tAML 相关细胞遗传学的经验 异常情况来确定该技术的敏感性。如果可以进行 FISH 被证明可以可靠地预测哪些患者处于发展的高风险 tMDS/tAML，这些患者应排除在 AHSCT 和替代疗法之外 可以采用治疗方法。