DETECTION OF MDS USING FISH IN PRETRANSPLANT SAMPLES

描述：(改编自研究人员摘要)联合治疗 骨髓增生异常综合征(TMDs)和急性髓系白血病(TAML) 在大剂量化疗后出现频率增加 自体造血干细胞移植(AHSCT)然而，TMD和 TAML也可在使用标准剂量的化疗和 治疗恶性肿瘤患者的放射治疗。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的病因分析。其他调查人员假设 以前接受过化疗和/或放射治疗的人 导致造血干细胞的细胞遗传学异常。这些 然后，干细胞被收集和存储，并回馈给患者 在大剂量治疗后。而TMDS/tAML随后被表示为POST AHSCT的病因是先治疗。标准细胞遗传学分析 移植前的骨髓样本被证明不够敏感 以可靠地检测哪些患者具有最高的发病风险 TMDS/tAML。然而，在一项使用FISH的试点研究中，12名患者中有9名患上了 AHSCT后的TMDs/tAML具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 对，是这样。在接受测试的患者中，没有一人进行了标准的细胞遗传学分析 中期核型检测细胞遗传学异常。这项提议将 推广FISH检测TMDS/tAML相关细胞遗传学的经验 以确定这项技术的敏感性。如果鱼可以 被证明可以可靠地预测哪些患者有发展的高风险 TMDS/tAML，这些患者应该被排除在AHSCT和替代方案之外 可以采用治疗方法。

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.