PO.CL04.02 · 临床研究
儿童急性髓系白血病临床和细胞遗传学特征的种族差异
Racial differences in clinical and cytogenetic features of pediatric acute myeloid leukemia
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
引言：儿童急性髓系白血病（AML）结局的种族差异已有充分记载，然而这些差异的生物学基础仍知之甚少。尽管分子技术已经可用，但其在刻画血统相关疾病变异方面的应用一直有限。在本研究中，我们旨在描绘儿童AML患者中与种族相关的临床和分子特征。
方法：我们利用了儿童TARGET AML 2018队列，该队列包含来自899名患者的临床、基因组和转录组数据。所有数据均通过cBioportal数据库检索和分析。分析仅限于至少有20例病例的种族组（白人、黑人/非裔美国人和亚裔）。分别采用卡方检验（X2）和Kruskal-Wallis检验比较分类特征和连续特征。
结果：在899名患者中，836名患者报告了种族数据，其中大多数为白人（n = 644，77.03%），其次是黑人/非裔美国人（n = 102，12.20%）、亚裔（n = 43，5.14%）和其他少数族裔（n=47，5.62%）。各种族组的诊断年龄相当（中位数11-12岁），亚裔患者的女性比例（61.22%）相较黑人/非裔美国人（50.88%）或白人（46.55%）患者呈现出增高的趋势（p = 0.255）。与白人患者相比，黑人/非裔美国人患者的总生存（OS）概率更差（HR：2.12，95% CI：1.46-3.1），而亚裔患者则无显著差异（HR：1.65，95% CI：0.98-2.8）。白人、亚裔和黑人/非裔美国人患者的中位OS分别为未达到、59个月和37个月。第一疗程结束时的可测量残留病（MRD）百分比因种族而显著不同（白人、黑人/非裔美国人、亚裔的中位数分别为0、0、0.12%，p = 0.0064）。在细胞遗传学异常中，t(6;11)(q27;q23)（p = 0.0022）和t(8;21)（p = 0.0059）在黑人/非裔美国人患者中最为富集（n = 6，5.26%；n = 23，20.18%），相比之下白人为（n = 9，1.29%；n = 82，11.78%），亚裔为（n = 1，2.08%；n = 6，12.5%）（p = 0.0022）。相反，inv(16)在白人患者中出现最频繁（n = 100，14.34%），相比之下黑人/非裔美国人为（n = 10，8.77%），亚裔为（n = 1，2.08%；p = 0.0029）。FLT3-ITD阳性率在亚裔患者中最高（n = 14，28.57%），其次是白人（n = 134，18.16%）和黑人/非裔美国人患者（n = 9，7.96%，p = 0.0039）。
结论：我们的研究结果凸显了儿童AML患者在结局和细胞遗传学特征方面与种族相关的临床变异性。黑人/非裔美国人患者的结局更差，且不良风险病变更多。这些模式表明，除社会经济因素外，潜在的内在生物学异质性可能是导致AML结局种族差异的原因，值得进一步开展基于血统的研究。
查看英文原文 English abstract
Introduction: Racial disparities in pediatric acute myeloid leukemia (AML) outcomes are well documented, yet the biological basis for these differences remains poorly understood. Despite the availability of molecular technologies, their use in characterizing ancestry-associated disease variation has been limited. In this study, we aimed to profile race-associated clinical and molecular features in pediatric patients with AML.
Methods: We utilized the pediatric TARGET AML 2018 cohort, which included samples from 899 patients with clinical, genomic, and transcriptomic data. All data were retrieved and analyzed through the cBioportal data repository. Analyses were limited to race groups with at least 20 cases (White, Black/African American, and Asian). X2 and Kruskal-Wallis tests were used to compare categorical and continuous features, respectively.
Results: Of 899 patients, 836 patients had data reported on race, of which the majority were White (n = 644, 77.03%), followed by Black/African American (n = 102, 12.20%), Asian (n = 43, 5.14%), and other racial minorities (n=47, 5.62%). Age at diagnosis was comparable across race groups (median 11-12), and there was a trend for increased female percentage in Asian patients (61.22%) compared to Black/African American (50.88%) or White (46.55%) patients (p = 0.255). Compared to White patients, Black/African American patients had worse overall survival (OS) probability (HR: 2.12, 95% CI: 1.46-3.1), while Asian patients did not have a significant difference (HR: 1.65, 95% CI: 0.98-2.8). Median OS was not reached, 59, and 37 months for White, Asian, and Black/African American patients, respectively. Measurable residual disease (MRD) percentage at the end of the first course of treatment varied significantly by race (median: 0, 0, 0.12% in White, Black/African American, Asian, respectively, p = 0.0064). Among cytogenetic abnormalities, t(6;11)(q27;q23) (p = 0.0022) and t(8;21) (p = 0.0059) were most enriched in Black/African American patients (n = 6, 5.26%, n = 23, 20.18%) compared with White (n = 9, 1.29%, n = 82, 11.78%) and Asian patients (n = 1, 2.08%; n = 6, 12.5%) p = 0.0022). In contrast, inv(16) occurred most frequently in White patients (n = 100, 14.34%) compared with Black/African American (n = 10, 8.77%) and Asian patients (n = 1, 2.08%; p = 0.0029). FLT3-ITD positivity was the highest in Asian patients (n = 14, 28.57%), followed by White (n = 134, 18.16%) and Black/African American patients (n = 9, 7.96%, p = 0.0039).
Conclusion: Our findings highlight race-associated clinical variability in outcomes and cytogenetic attributes across pediatric AML patients. Black/African American patients had worse outcomes and more adverse-risk lesions. These patterns show that, beyond socioeconomic factors, potential underlying biological heterogeneity may contribute to racial disparities in AML outcomes and warrant further ancestry-driven investigations.
利益披露 Disclosure
S. Elbanna, None..
H. M. Abushukair, None.