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Correlation between microsatellite discrepancy scores and transplant outcome after haemopoietic SCT for pediatric ALL

机译:小儿ALL造血SCT后微卫星差异评分与移植结果的相关性

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Microsatellite analyses show that self-reported ethnicity often correlates poorly with true genetic ancestry. As unknown ancestral differences could potentially have an impact on transplant outcome, we developed an average allele length discrepancy (AALD) score to assess allele length discrepancy between donor/recipient (D/R) using microsatellites analysed routinely in post-transplant chimeric assessment. This was then compared with outcome in a homogeneously treated cohort of pediatric patients undergoing high-resolution sibling or matched unrelated donor transplantation for acute lymphoblastic leukemia (ALL). AALD scores formed a numeric continuum ranging from 0 to 1.4 (median 0.76) for sibling pairs and 0.8-2.17 (median 1.6) for high-resolution matched unrelated donor (HR-MUD) pairs. There was a trend for worse OS with increasing AALD score, which reached statistical significance above a threshold of 1.7 for OS. Patients whose transplants had an AALD score of >= 1.8 had a risk of non-relapse mortality 4.9 times greater (P = 0.025) and relapse risk three times greater (P = 0.058) than those scoring < 1.8. This approach will now be explored in a Centre International for Blood and Marrow Transplantation Research (CIBMTR) study of 750 D/R pairs across all disease groups; if confirmed, it has the potential to improve donor selection for patients with multiple prospective donors.
机译:微卫星分析表明,自我报告的种族常常与真实的遗传血统关系不佳。由于未知的祖先差异可能会对移植结果产生影响,因此,我们开发了平均等位基因长度差异(AALD)评分,以使用移植后嵌合评估中常规分析的微卫星评估供体/受体(D / R)之间的等位基因长度差异。然后将其与接受高分辨率同胞或配对无关供体移植的急性淋巴细胞白血病(ALL)的小儿患者的均一治疗队列中的结果进行比较。对于同级兄弟对,AALD得分形成了一个从0到1.4(中位数0.76)的数字连续范围,对于高分辨率匹配的非相关供体(HR-MUD)对,AALD评分范围从0到1.4(中位数0.76)。随着AALD分数的增加,存在OS恶化的趋势,达到OS阈值1.7以上的统计学显着性。移植的AALD评分> = 1.8的患者发生非复发死亡率的风险是那些得分<1.8的患者的4.9倍(P = 0.025),复发风险的三倍(P = 0.058)。现在将在国际血液和骨髓移植研究中心(CIBMTR)对所有疾病组的750个D / R对的研究中探索这种方法。如果得到确认,则有可能改善具有多个预期供体的患者的供体选择。

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