DETECTION OF MDS USING FISH IN PRETRANSPLANT SAMPLES

使用移植前样本中的鱼检测 MDS

• 批准号: 6283617
• 负责人: DAVID D HURD
• 金额: $ 16.31万
• 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 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6283617
• 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：（根据研究者的摘要进行了改编）与治疗相关的治疗 骨髓增生综合征（TMDS）和急性骨髓性白血病（TAML）具有 在高剂量化疗和 自体造血干细胞移植（AHSCT）。但是，TMD和 使用标准剂量的化学疗法和 治疗患者恶性肿瘤的辐射。一些调查人员有 假设移植的制备方案是主要的 AHSCT TMDS/TAML的病因。其他调查人员已经假设 正是接触先前的化学疗法和/或放射治疗 引起造血干细胞的细胞遗传学异常。这些 然后收集和存储干细胞，并将其还给患者 遵循高剂量疗法。随后表示TMDS/TAML AHSCT，病因是先前的治疗方法。标准细胞遗传学分析 移植前的骨髓样品尚未证明足够敏感 可靠地检测哪些患者的发展风险最高 TMDS/TAML。但是，在一项使用鱼的试点研究中，有12名患者中有9名 发现AHSCT之后的TMDS/TAML具有相同的细胞遗传学异常 在移植前样品中，强烈表明后一种假设是 正确的。在没有测试的患者中，没有进行标准的细胞遗传学分析 中期核型检测细胞遗传学异常。该提议将 扩大使用鱼检测TMD/TAML相关的细胞遗传学的经验 确定此技术敏感性的异常。如果可以鱼 证明可以可靠地预测哪些患者有发展的高风险 TMDS/TAML，应将这些患者排除在AHSCT和替代方案之外 可以采用治疗方法。