Originally published as JCO Early Release 10.1200/JCO.2007.12.8298 on December 17 2007

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Canioni, D. Articles by Xerri, L. Search for Related Content PubMed PubMed Citation Articles by Canioni, D. Articles by Xerri, L. Social Bookmarking                            What's this?

High Numbers of Tumor-Associated Macrophages Have an Adverse Prognostic Value That Can Be Circumvented by Rituximab in Patients With Follicular Lymphoma Enrolled Onto the GELA-GOELAMS FL-2000 Trial

Danielle Canioni, Gilles Salles, Nicolas Mounier, Nicole Brousse, Marie Keuppens, Frank Morchhauser, Thierry Lamy, Anne Sonet, Marie-Christine Rousselet, Charles Foussard, Luc Xerri

From the Department of Pathology, Assistance Publique-Hopitaux de Paris, Hôpital Necker-Enfants Malades; Université Paris-Descartes, Paris; Department of Hematology, Hospices Civils de Lyon; Université Lyon 1, Lyon; Department of Hematology, Centre Hospitalo-Universitaire, Nice; Department of Hematology, Centre Hospitalier, Lille; Department of Hematology, Centre Hospitalier, Rennes; Departments of Pathology and Hematology Hôpital d'Angers, Angers; Department of Bio-Pathology, Institut Paoli-Calmettes; Université de la Méditerranée, Marseille, France; and Department of Hematology, Hopital Universitaire de Mont-Godinne, Yvoir, Belgium

Corresponding author: Danielle Canioni, MD, Department of Pathology, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015, Paris, France; e-mail: danielle.canioni{at}nck.ap-hop-paris.fr

Purpose High amounts of intratumoral macrophages have been shown to correlate with poor prognosis in patients with follicular lymphoma (FL) treated with chemotherapy without rituximab. We tried to establish whether intratumoral macrophage count (MC) definitely is able to predict the outcome of FL patients in the rituximab era.

Patients and Methods We analyzed immunohistochemical CD68 expression in 194 FL patients from the FL-2000 trial, randomly assigned to receive cyclophosphamide, doxorubicin, etoposide, prednisolone, and interferon (CHVP-I) or rituximab plus CHVP-I. Immunohistochemistry was performed on paraffin sections using anti-CD68 KP1 antibody, and stained macrophages were scored on high-power field (hpf) in either intrafollicular (IF) or extrafollicular (EF) areas.

Results For IF MC, the best cutoff point was estimated at 10 macrophages/hpf. Low IF MC was significantly associated with a better event-free survival (EFS; P = .011). However, this effect was observed only in the CHVP-I arm (P = .012) and not in the rituximab plus CHVP-I arm. Using a cutoff of 15 IF MC, we found no significant association with EFS. For EF MC, fewer than 22 macrophages/hpf were associated with better EFS in the CHVP-I arm (P = .02) but not in the rituximab plus CHVP-I arm.

Conclusion These results show that MC can predict outcome of FL patients and that rituximab is able to circumvent the unfavorable outcome associated with high MC.

published online ahead of print at www.jco.org on December 17, 2007.

Supported by the Programme Hospitalier de Recherche Clinique (Hospices Civils de Lyon, PHRC 2000-081) and the Ligue Nationale Contre le Cancer.

Presented in part at the Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. W. Sweetenham, B. Goldman, M. L. LeBlanc, J. R. Cook, R. R. Tubbs, O. W. Press, D. G. Maloney, R. I. Fisher, L. M. Rimsza, R. M. Braziel, et al. Prognostic value of regulatory T cells, lymphoma-associated macrophages, and MUM-1 expression in follicular lymphoma treated before and after the introduction of monoclonal antibody therapy: a Southwest Oncology Group Study Ann. Onc., October 29, 2009; (2009) mdp460v1. [Abstract] [Full Text] [PDF]

				M. Leidi, E. Gotti, L. Bologna, E. Miranda, M. Rimoldi, A. Sica, M. Roncalli, G. A. Palumbo, M. Introna, and J. Golay M2 Macrophages Phagocytose Rituximab-Opsonized Leukemic Targets More Efficiently than M1 Cells In Vitro J. Immunol., April 1, 2009; 182(7): 4415 - 4422. [Abstract] [Full Text] [PDF]

				C. Kadoch, E. B. Dinca, R. Voicu, L. Chen, D. Nguyen, S. Parikh, J. Karrim, M. A. Shuman, C. A. Lowell, P. A. Treseler, et al. Pathologic Correlates of Primary Central Nervous System Lymphoma Defined in an Orthotopic Xenograft Model Clin. Cancer Res., March 15, 2009; 15(6): 1989 - 1997. [Abstract] [Full Text] [PDF]

				J. Ruan, K. Hajjar, S. Rafii, and J. P. Leonard Angiogenesis and antiangiogenic therapy in non-Hodgkin's lymphoma Ann. Onc., March 1, 2009; 20(3): 413 - 424. [Abstract] [Full Text] [PDF]

				M. E. Juweid, G. J. Weiner, B. K. Link, S. J. Horning, and G. A. Wiseman Measuring Granulocyte and Monocyte Accumulation at Malignant Lymphoma Sites J. Clin. Oncol., January 1, 2009; 27(1): 154 - 155. [Full Text] [PDF]

				M. Lejeune and T. Alvaro Clinicobiological, prognostic and therapeutic implications of the tumor microenvironment in follicular lymphoma Haematologica, January 1, 2009; 94(1): 16 - 21. [Full Text] [PDF]

				D. de Jong, A. Koster, A. Hagenbeek, J. Raemaekers, D. Veldhuizen, S. Heisterkamp, J. P. de Boer, and M. van Glabbeke Impact of the tumor microenvironment on prognosis in follicular lymphoma is dependent on specific treatment protocols Haematologica, January 1, 2009; 94(1): 70 - 77. [Abstract] [Full Text] [PDF]

				N. A. Johnson and R. D. Gascoyne Gene expression signatures in follicular lymphoma: are they ready for the clinic? Haematologica, July 1, 2008; 93(7): 982 - 987. [Full Text] [PDF]

				M. Taskinen, M.-L. Karjalainen-Lindsberg, and S. Leppa Prognostic influence of tumor-infiltrating mast cells in patients with follicular lymphoma treated with rituximab and CHOP Blood, May 1, 2008; 111(9): 4664 - 4667. [Abstract] [Full Text] [PDF]