Prognostic Model to Predict Post-Autologous Stem-Cell Transplantation Outcomes in Classical Hodgkin Lymphoma
Prognostic Model to Predict Post-Autologous Stem-Cell Transplantation Outcomes in Classical Hodgkin Lymphoma
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DOI：
10.1200/jco.2017.72.7925
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发表时间：
2017-11-10
影响因子：
45.3
通讯作者：
Steidl, Christian
中科院分区：
文献类型：
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作者：
Chan, Fong Chun;Mottok, Anja;Steidl, Christian
目的我们的目的是捕获经典霍奇金淋巴瘤（cHL）复发时的生物学，并发现预测自体干细胞移植（ASCT）后结果的新的和可靠的生物标志物。材料和方法我们对来自174名cHL患者的245份福尔马林固定的石蜡包埋肿瘤标本的队列进行了数字基因表达谱分析，包括71例在初次诊断和复发时进行活检的患者，以研究时间基因表达差异及其与ASCT后结局的相关性。复发活检从一个训练队列的65例患者被用来建立一个基因表达为基础的预后模型后ASCT的结果（RHL 30），和两个独立的coholsforvalidation.ResultsGene表达谱显示，24%的患者表现出不良相关的表达模式之间的活检在最初的诊断和复发，表明生物分歧。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包含ASCT后结局预测的上级特性。我们使用复发标本开发了RHL 30，在两个独立的外部验证队列中确定了ASCT后结局较差的高危患者子集。RHL 30的预后能力是独立的临床预后标志物（无论是在最初的诊断和复发）和微环境成分评估通过immunohistochemistry.ConclusionWe已经开发和验证了一种新的临床适用的预后检测，在第一次复发时确定患者不利的ASCT后的结果。展望未来，在正电子发射断层扫描引导的缓解评估和不断发展的cHL治疗前景的背景下评价RHL 30的临床使用至关重要。(C)2017年美国临床肿瘤学会
PurposeOur 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 MethodsWe 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.ResultsGene 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.ConclusionWe 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. (C) 2017 by American Society of Clinical Oncology