Upcoming diagnostic and therapeutic developments in classical Hodgkin's lymphoma

With improvements in therapy, increasing dose intensity, early recognition of toxicity, and enhanced supportive care, current outcomes in patients with classical Hodgkin's lymphoma (HL) may be superior to disease-free and overall survival (OS) predicted by existing prognostic models, including the International Prognostic Score (IPS). The addition of biologic markers to recognized clinical prognostic factors, including those of the IPS, may to improve patient risk stratification and guide therapy in the future. However, the identification of these markers has been problematic due to the lack of large, confirmatory prospective trials, reproducibility and feasibility of the assays, and failure to improve upon already recognized clinical risk factors. One biomarker in particular, CD68, present on tumor infiltrating macrophages and detectable by immunohistochemical staining, is significantly associated with both shortened progression-free and disease-specific survivals in patients with HL at diagnosis and at relapse. In addition, less than 5% CD68+ cells correlates with a 100% disease-specific survival in patients with early-stage HL. CD68 represents just one of the many prognostic markers that could eventually be used to risk-stratify therapy. In addition, biologic markers may not only serve as prognostic markers, but also as therapeutic targets in HL. This review examines current data using the IPS to determine patient outcome, discuss several potential biologic prognostic markers, and summarize new therapies that are currently in clinical development in HL.