Gene expression-based outcome prediction in advanced stage classical Hodgkin lymphoma treated with BEACOPP

Abstract

Classical Hodgkin Lymphoma (cHL) is a B cell-derived lymphoid malignancy, affecting 2.5–3/100,000 people per year. To date, in patients diagnosed with advanced cHL no reliable tool is able to—a priori—distinguish the subset of patients at high risk for relapse or refractory disease. Clinical risk indices for cHL, such as the International Prognostic Score (IPS), have not been successfully applied as a treatment decision tool in advanced stage cHL [1]. In this study we show, that a previously published gene expression-based predictor in advanced stage cHL patients treated with ABVD [2] does not prove prognostic in 401 BEACOPP-treated advanced stage cHL patients. Using transcriptome profiling, we identified however that three individual genes, PDGFRA, TNFRSF8 (encoding CD30) and CCL17 (encoding TARC), were significantly associated with progression-free survival (PFS) after multiple test correction in the BEACOPP-treated cohort, highlighting the potential of a modified gene expression profiling approach for pre-treatment risk assessment. In search of a predictive tool in advanced stage cHL patients, we have applied the previously published 23-gene gene expression‐based predictor [2], that is prognostic for overall survival (OS) in patients with locally extensive and advanced stage disease treated with ABVD chemotherapy in a distinct cohort of patients with advanced-stage cHL patients treated with BEACOPP-based regimens. In particular, we explored the relationship of the predictor score These authors contributed equally: Ron D. Jachimowicz, Wolfram Klapper