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 journalArticle

761 Citations (Scopus)

Abstract

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
Volume362
Issue number10
DOIs
StatePublished - Mar 11 2010

Fingerprint

Hodgkin Disease
Macrophages
Survival
Neoplasms
Gene Expression Profiling
Biomarkers
Hematopoietic Stem Cell Transplantation
Treatment Failure
Disease-Free Survival
Multivariate Analysis
Cell Count
Lymph Nodes
Biopsy
Recurrence
Therapeutics
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Steidl, C., Lee, T., Shah, S. P., Farinha, P., Han, G., Nayar, T., ... Gascoyne, R. D. (2010). Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. New England Journal of Medicine, 362(10), 875-885. https://doi.org/10.1056/NEJMoa0905680

Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. / Steidl, Christian; Lee, Tang; Shah, Sohrab P.; Farinha, Pedro; Han, Guangming; Nayar, Tarun; Delaney, Allen; Jones, Steven J.; Iqbal, Javeed; Weisenburger, Dennis D.; Bast, Martin A.; Rosenwald, Andreas; Muller-Hermelink, Hans Konrad; Rimsza, Lisa M.; Campo, Elias; Delabie, Jan; Braziel, Rita M.; Cook, James R.; Tubbs, Ray R.; Jaffe, Elaine S.; Lenz, Georg; Connors, Joseph M.; Staudt, Louis M.; Chan, Wing C.; Gascoyne, Randy D.

In: New England Journal of Medicine, Vol. 362, No. 10, 11.03.2010, p. 875-885.

Research output: Contribution to journalArticle

Steidl, C, Lee, T, Shah, SP, Farinha, P, Han, G, Nayar, T, Delaney, A, Jones, SJ, Iqbal, J, Weisenburger, DD, Bast, MA, Rosenwald, A, Muller-Hermelink, HK, Rimsza, LM, Campo, E, Delabie, J, Braziel, RM, Cook, JR, Tubbs, RR, Jaffe, ES, Lenz, G, Connors, JM, Staudt, LM, Chan, WC & Gascoyne, RD 2010, 'Tumor-associated macrophages and survival in classic Hodgkin's lymphoma', New England Journal of Medicine, vol. 362, no. 10, pp. 875-885. https://doi.org/10.1056/NEJMoa0905680
Steidl, Christian ; Lee, Tang ; Shah, Sohrab P. ; Farinha, Pedro ; Han, Guangming ; Nayar, Tarun ; Delaney, Allen ; Jones, Steven J. ; Iqbal, Javeed ; Weisenburger, Dennis D. ; Bast, Martin A. ; Rosenwald, Andreas ; Muller-Hermelink, Hans Konrad ; Rimsza, Lisa M. ; Campo, Elias ; Delabie, Jan ; Braziel, Rita M. ; Cook, James R. ; Tubbs, Ray R. ; Jaffe, Elaine S. ; Lenz, Georg ; Connors, Joseph M. ; Staudt, Louis M. ; Chan, Wing C. ; Gascoyne, Randy D. / Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. In: New England Journal of Medicine. 2010 ; Vol. 362, No. 10. pp. 875-885.
@article{819b1745881e4a4398034e1d2b0045d5,
title = "Tumor-associated macrophages and survival in classic Hodgkin's lymphoma",
abstract = "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.",
author = "Christian Steidl and Tang Lee and Shah, {Sohrab P.} and Pedro Farinha and Guangming Han and Tarun Nayar and Allen Delaney and Jones, {Steven J.} and Javeed Iqbal and Weisenburger, {Dennis D.} and Bast, {Martin A.} and Andreas Rosenwald and Muller-Hermelink, {Hans Konrad} and Rimsza, {Lisa M.} and Elias Campo and Jan Delabie and Braziel, {Rita M.} and Cook, {James R.} and Tubbs, {Ray R.} and Jaffe, {Elaine S.} and Georg Lenz and Connors, {Joseph M.} and Staudt, {Louis M.} and Chan, {Wing C.} and Gascoyne, {Randy D.}",
year = "2010",
month = "3",
day = "11",
doi = "10.1056/NEJMoa0905680",
language = "English (US)",
volume = "362",
pages = "875--885",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "10",

}

TY - JOUR

T1 - Tumor-associated macrophages and survival in classic Hodgkin's lymphoma

AU - Steidl, Christian

AU - Lee, Tang

AU - Shah, Sohrab P.

AU - Farinha, Pedro

AU - Han, Guangming

AU - Nayar, Tarun

AU - Delaney, Allen

AU - Jones, Steven J.

AU - Iqbal, Javeed

AU - Weisenburger, Dennis D.

AU - Bast, Martin A.

AU - Rosenwald, Andreas

AU - Muller-Hermelink, Hans Konrad

AU - Rimsza, Lisa M.

AU - Campo, Elias

AU - Delabie, Jan

AU - Braziel, Rita M.

AU - Cook, James R.

AU - Tubbs, Ray R.

AU - Jaffe, Elaine S.

AU - Lenz, Georg

AU - Connors, Joseph M.

AU - Staudt, Louis M.

AU - Chan, Wing C.

AU - Gascoyne, Randy D.

PY - 2010/3/11

Y1 - 2010/3/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77949345555&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949345555&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa0905680

DO - 10.1056/NEJMoa0905680

M3 - Article

C2 - 20220182

AN - SCOPUS:77949345555

VL - 362

SP - 875

EP - 885

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 10

ER -