Purpose Our aim was to capture the biology of classical Hodgkin lymphoma (cHL) at the time of relapse and discover novel and robust biomarkers that predict outcomes after autologous stem-cell transplantation (ASCT). Materials and Methods We performed digital gene expression profiling on a cohort of 245 formalin-fixed, paraffin-embedded tumor specimens from 174 patients with cHL, including 71 with biopsies taken at both primary diagnosis and relapse, to investigate temporal gene expression differences and associations with post-ASCT outcomes. Relapse biopsies from a training cohort of 65 patients were used to build a gene expression-based prognostic model of post-ASCT outcomes (RHL30), and two independent cohorts were used for validation. Results Gene expression profiling revealed that 24% of patients exhibited poorly correlated expression patterns between their biopsies taken at initial diagnosis and relapse, indicating biologic divergence. Comparative analysis of the prognostic power of gene expression measurements in primary versus relapse specimens demonstrated that the biology captured at the time of relapse contained superior properties for post-ASCT outcome prediction. We developed RHL30, using relapse specimens, which identified a subset of high-risk patients with inferior post-ASCT outcomes in two independent external validation cohorts. The prognostic power of RHL30 was independent of reported clinical prognostic markers (both at initial diagnosis and at relapse) and microenvironmental components as assessed by immunohistochemistry. Conclusion We have developed and validated a novel clinically applicable prognostic assay that at the time of first relapse identifies patients with unfavorable post-ASCT outcomes. Moving forward, it will be critical to evaluate the clinical use of RHL30 in the context of positron emission tomography-guided response assessment and the evolving cHL treatment landscape.

中文翻译：

---

预测经典霍奇金淋巴瘤自体干细胞移植后结果的预后模型

目的我们的目标是在复发时捕捉经典霍奇金淋巴瘤 (cHL) 的生物学特性，并发现预测自体干细胞移植 (ASCT) 后结果的新型且强大的生物标志物。材料和方法 我们对来自 174 名 cHL 患者的 245 份福尔马林固定、石蜡包埋的肿瘤标本进行了数字基因表达谱分析，其中 71 名在初次诊断和复发时都进行了活检，以研究时间基因表达差异及其相关性。 ASCT 后的结果。来自 65 名患者的训练队列的复发活检用于构建基于基因表达的 ASCT 后结果预后模型 (RHL30)，并使用两个独立队列进行验证。结果 基因表达谱显示，24% 的患者在初始诊断和复发时进行的活组织检查之间表现出相关性较差的表达模式，表明生物学差异。对原发与复发标本中基因表达测量的预后能力的比较分析表明，复发时捕获的生物学具有用于 ASCT 后结果预测的优越特性。我们使用复发样本开发了 RHL30，它在两个独立的外部验证队列中确定了一部分 ASCT 后结果较差的高风险患者。RHL30 的预后能力独立于报告的临床预后标志物（初始诊断和复发时）和免疫组织化学评估的微环境成分。结论我们已经开发并验证了一种新的临床适用的预后检测方法，可在首次复发时识别具有不利 ASCT 后结果的患者。展望未来，在正电子发射断层扫描引导的反应评估和不断发展的 cHL 治疗环境中评估 RHL30 的临床应用将是至关重要的。