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：（改编自研究者摘要）治疗相关 骨髓增生异常综合征（tMDS）和急性髓细胞性白血病（tAML）具有 在高剂量化疗后， 自体造血干细胞移植（AHSCT）。然而，tMDS和 tAML也可以在使用标准剂量的化疗后发展， 用于治疗恶性肿瘤患者的放射治疗。一些调查人员 假设移植的准备方案是主要的 AHSCT后tMDS/tAML的病因。其他研究人员假设 暴露于先前的化疗和/或放疗， 导致造血干细胞的细胞遗传学异常。这些 然后收集和储存干细胞，并将其还给患者。 高剂量治疗后。而tMDS/tAML随后表达后， AHSCT的病因是既往治疗。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 以可靠地检测哪些患者处于发展的最高风险， tMDS/tAML。然而，在一项使用FISH的试点研究中，12名患者中有9名 AHSCT后的tMDS/tAML也有相同的细胞遗传学异常 在移植前的样本中，强烈表明后一种假设是 正确.在所有受试患者中，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。这项建议会 扩大FISH检测tMDS/tAML相关细胞遗传学的经验 以确定该技术的灵敏度。如果鱼可以 可以可靠地预测哪些患者处于发展的高风险中， tMDS/tAML，这些患者应从AHSCT中排除， 可以采取治疗方法。