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Annals of Oncology Advance Access published online on May 12, 2007
Annals of Oncology, doi:10.1093/annonc/mdm110
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© 2007 European Society for Medical Oncology

Peripheral blood natural killer cell count is associated with clinical outcome in patients with aaIPI 2–3 diffuse large B-cell lymphoma

A Plonquet1, C Haioun2, J-P Jais3, A-L Debard4, G Salles5, M-C Bene6, P Feugier7, C Rabian8, O Casasnovas9, M Labalette10, E Kuhlein11, J-P Farcet1, J-F Emile12, C Gisselbrecht13, M-H Delfau-Larue1,* On behalf of GELA (Groupe d'étude des lymphomes de l'adulte)

1 Service d'Immunologie Biologique, Institut National de la Santé et de la Recherche Médicale (INSERM), U617, Créteil
2 Service d'Hématologie clinique, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Henri Mondor-Albert Chenevier, Université Paris 12, Faculté de Médecine, Créteil
3 Faculté de Médecine, Université René Descartes, AP-HP, Hôpital Necker-Enfants Malades, Service de Biostatistique et Informatique Médicale, Paris
4 Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Pierre Bénite, Lyon
5 Service d'Hématologie, Hospices Civils de Lyon, Pierre-Bénite
6 Laboratoire d'Immunologie Centre Hospitalier Universitaire (CHU) Nancy Brabois, Vandoeuvre les Nancy
7 Service d' Hématologie Adulte, Faculté de Médecine, Université Henri Poincaré Nancy 1, CHU Nancy Brabois, Vandoeuvre les Nancy
8 Laboratoire d'Immunologie et Histocompatibilité, Université Paris 7, AP-HP, Hôpital Saint-Louis, Paris
9 Service d'Hematologie Clinique, CHU Dijon, Dijon
10 Laboratoire d'Immunologie, EA 2686 CHRU Lille
11 Laboratoire d'Immunologie, CHU Rangueil, Toulouse
12 Service d'Anatomie Pathologique, INSERM U602, Université Versailles-Saint Quentin, AP-HP, Hôpital Ambroise Pare, Boulogne
13 Service d'Hématologie–Oncologie Adultes, Université Paris 7, AP-HP, Hôpital Saint-Louis, Paris, France

* Correspondence to: Prof. M.-H. Delfau-Larue, Laboratoire d'Immunologie Biologique—Hôpital Henri Mondor, 51, ave du Maréchal de Lattre de Tassigny, 94010 Creteil, France. Tel: +33-1-49-81-26-65; Fax: +33-1-49-81-28-97; E-mail: marie-helene.delfau-larue{at}hmn.aphp.fr

Background: Lymphocytopenia is a prognostic factor in Hodgkin's disease. In diffuse large B-cell lymphoma (DLBCL), data are much less established, in spite of numerous reports on immune system–lymphoma interactions. This study addresses the prognostic value of blood lymphocyte subsets at diagnosis in DLBCL.

Patients and methods: Absolute values of blood lymphocyte subsets and monocytes were prospectively determined by flow cytometry in 140 patients with 2 or 3 adverse age-adjusted International Prognostic Index (aaIPI) factors included in a Groupe d'Etude des Lymphomes de l'Adulte protocol (LNH98B3). Absolute cell counts at diagnosis and aaIPI were evaluated with regard to clinical outcome.

Results: Low median cell counts of 337, 211, and 104/µl were evidenced for the CD4+, CD8+ T, and natural killer (NK) cells, respectively. In univariate analysis, only NK cell count [odds ratio (OR) = 1.81 (1.27, 2.57), P = 0.001] and aaIPI [OR = 2.29 (0.95, 5.45), P = 0.06] were associated with induction treatment response. Low NK cell count [Hazard ratio (HR) = 1.27 (1.06, 1.52), P = 0.01] and aaIPI 3 [HR = 1.95 (1.20, 3.16), P = 0.01] were also associated with a shorter event free survival (EFS). In multivariate analysis, NK cell count was associated with response [OR = 1.77 (1.24, 2.54), P = 0.002] and EFS [HR = 1.25 (1.04, 1.50) P = 0.02] independently of aaIPI.

Conclusions: This study shows an association between circulating NK cell number and clinical outcome in DLBCL, possibly important in the context of the broadening use of rituximab, a likely NK-dependant therapy.

Diffuse large B-cell lymphoma, lymphopenia, NK cells, prognosis

Received for publication November 27, 2006. Revision received February 2, 2007. Accepted for publication February 21, 2007.


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