Tumor-associated macrophages and survival in classic Hodgkin's lymphoma

Christian Steidl, Tang Lee, Sohrab P. Shah, Pedro Farinha, Guangming Han, Tarun Nayar, Allen Delaney, Steven J. Jones, Javeed Iqbal, Dennis D. Weisenburger, Martin A. Bast, Andreas Rosenwald, Hans Konrad Muller-Hermelink, Lisa M. Rimsza, Elias Campo, Jan Delabie, Rita M. Braziel, James R. Cook, Ray R. Tubbs, Elaine S. JaffeGeorg Lenz, Joseph M. Connors, Louis M. Staudt, Wing C. Chan, Randy D. Gascoyne

Research output: Contribution to journalArticlepeer-review

1072 Scopus citations


Background: Despite advances in treatments for Hodgkin's lymphoma, about 20% of patients still die from progressive disease. Current prognostic models predict the outcome of treatment with imperfect accuracy, and clinically relevant biomarkers have not been established to improve on the International Prognostic Score. Methods: Using gene-expression profiling, we analyzed 130 frozen samples obtained from patients with classic Hodgkin's lymphoma during diagnostic lymph-node biopsy to determine which cellular signatures were correlated with treatment outcome. We confirmed our findings in an independent cohort of 166 patients, using immunohistochemical analysis. Results: Gene-expression profiling identified a gene signature of tumor-associated macrophages that was significantly associated with primary treatment failure (P = 0.02). In an independent cohort of patients, we found that an increased number of CD68+ macrophages was correlated with a shortened progression-free survival (P = 0.03) and with an increased likelihood of relapse after autologous hematopoietic stem-cell transplantation (P = 0.008), resulting in shortened disease-specific survival (P = 0.003). In multivariate analysis, this adverse prognostic factor outperformed the International Prognostic Score for disease-specific survival (P = 0.003 vs. P = 0.03). The absence of an elevated number of CD68+ cells in patients with limited-stage disease defined a subgroup of patients with a long-term disease-specific survival of 100% with the use of current treatment strategies. Conclusions: An increased number of tumor-associated macrophages was strongly associated with shortened survival in patients with classic Hodgkin's lymphoma and provides a new biomarker for risk stratification.

Original languageEnglish (US)
Pages (from-to)875-885
Number of pages11
JournalNew England Journal of Medicine
Issue number10
StatePublished - Mar 11 2010

ASJC Scopus subject areas

  • General Medicine


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