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

Ann Oncol. 2007 Jul;18(7):1209-15. doi: 10.1093/annonc/mdm110. Epub 2007 May 12.

Abstract

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/mul 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-dependent therapy.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B-Lymphocytes / cytology
  • Bleomycin / administration & dosage
  • CD4-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / cytology
  • Cell Count
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Kaplan-Meier Estimate
  • Killer Cells, Natural / cytology*
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / immunology*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphopenia*
  • Male
  • Middle Aged
  • Monocytes / cytology
  • Peripheral Blood Stem Cell Transplantation
  • Rituximab
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Bleomycin
  • Rituximab
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide

Supplementary concepts

  • AC protocol
  • ACE protocol 1
  • ACVB protocol