1. A gene expression-based model predicts outcome in children with intermediate-risk classical Hodgkin lymphoma
- Author
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Randy D. Gascoyne, Lydia Visser, Debra L. Friedman, Terzah M. Horton, Rebecca L. Johnston, Kara M. Kelly, Christian Steidl, Cindy L. Schwartz, Aixiang Jiang, Anja Mottok, Arjan Diepstra, David Scott, Adele Telenius, Fong Chun Chan, and Stem Cell Aging Leukemia and Lymphoma (SALL)
- Subjects
Oncology ,medicine.medical_specialty ,Stromal cell ,medicine.medical_treatment ,Immunology ,Disease ,Malignancy ,Biochemistry ,Models, Biological ,Internal medicine ,medicine ,Tumor Microenvironment ,Humans ,Stage (cooking) ,Child ,Chemotherapy ,Tumor microenvironment ,business.industry ,Gene Expression Profiling ,Cell Biology ,Hematology ,medicine.disease ,Prognosis ,Hodgkin Disease ,Progression-Free Survival ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,TUMOR-ASSOCIATED MACROPHAGES ,Toxicity ,business - Abstract
Classical Hodgkin lymphoma (cHL) is a common malignancy in children and adolescents. Although cHL is highly curable, treatment with chemotherapy and radiation often come at the cost of long-term toxicity and morbidity. Effective risk-stratification tools are needed to tailor therapy. Here, we used gene expression profiling (GEP) to investigate tumor microenvironment (TME) biology, to determine molecular correlates of treatment failure, and to develop an outcome model prognostic for pediatric cHL. A total of 246 formalin-fixed, paraffin-embedded tissue biopsies from patients enrolled in the Children’s Oncology Group trial AHOD0031 were used for GEP and compared with adult cHL data. Eosinophil, B-cell, and mast cell signatures were enriched in children, whereas macrophage and stromal signatures were more prominent in adults. Concordantly, a previously published model for overall survival prediction in adult cHL did not validate in pediatric cHL. Therefore, we developed a 9-cellular component model reflecting TME composition to predict event-free survival (EFS). In an independent validation cohort, we observed a significant difference in weighted 5-year EFS between high-risk and low-risk groups (75.2% vs 90.3%; log-rank P = .0138) independent of interim response, stage, fever, and albumin. We demonstrate unique disease biology in children and adolescents that can be harnessed for risk-stratification at diagnosis. This trial was registered at www.clinicaltrials.gov as #NCT00025259.
- Published
- 2022