Prognostic Model to Predict Post-Autologous Stem-Cell Transplantation Outcomes in Classical Hodgkin Lymphoma

Fong Chun Chan, Anja Mottok, Alina S. Gerrie, Maryse Power, Marcel Nijland, Arjan Diepstra, Anke van den Berg, Peter Kamper, Francesco d'Amore, Alexander Lindholm d'Amore, Stephen Hamilton-Dutoit, Kerry J. Savage, Sohrab P. Shah, Joseph M. Connors, Randy D. Gascoyne, David W. Scott, Christian Steidl*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Purpose: 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).

Materials and Methods: 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.

Results: 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.

Conclusion: 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.

Original languageEnglish
Pages (from-to)3722-3733
Number of pages14
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume35
Issue number32
DOIs
Publication statusPublished - 10-Nov-2017

Keywords

  • REGULATORY T-CELLS
  • TUMOR-ASSOCIATED MACROPHAGES
  • HIGH-DOSE CHEMOTHERAPY
  • GENE-EXPRESSION
  • BRENTUXIMAB VEDOTIN
  • CLONAL EVOLUTION
  • 1ST RELAPSE
  • DISEASE
  • MICROENVIRONMENT
  • PHASE-2

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