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).

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.

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.

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.

我们的目标是在复发时捕获经典霍奇金淋巴瘤（cHL）的生物学特性，并发现能够预测自体干细胞移植（ASCT）后结果的新颖而强大的生物标记物。

我们对来自174例cHL患者的245例福尔马林固定，石蜡包埋的肿瘤标本进行了数字基因表达谱分析，包括在初次诊断和复发时进行的71例活检，以调查时间基因表达差异以及与ASCT后的关联结果。来自65名患者的训练队列的复发活检用于建立ASCT后结果（RHL30）的基于基因表达的预后模型，并使用两个独立的队列进行验证。

基因表达谱分析显示，有24％的患者在最初诊断和复发之间的活检组织之间表现出很弱的相关表达模式，表明存在生物学差异。对原发和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信息具有ASCT后结果预测的优良特性。我们使用复发标本开发了RHL30，该标本在两个独立的外部验证队列中确定了ASCT后结果较差的高风险患者。RHL30的预后能力独立于已报道的临床预后标志物（在初步诊断和复发时）以及通过免疫组织化学评估的微环境成分。

我们已经开发并验证了一种新的临床可应用的预后测定方法，该方法可在首次复发时识别出ASCT后预后不良的患者。展望未来，在正电子发射断层摄影术指导的反应评估和不断发展的cHL治疗环境中评估RHL30的临床应用至关重要。