Cellular Immunodeficiency in Untreated Lymphoma Patients.

Abstract

The association of lymphoma with a plethora of secondary immune defects is well established. However, most investigations were performed many years ago and little is known about disease specific alterations of the immune system. The availability of new diagnostic methods and a new classification of hematologic diseases (WHO 2000) makes a newly designed study of the immuno-dysfunction in this patient group worthwhile. From January 2003 to August 2004 50 patients with newly diagnosed malignant hematologic diseases - diffuse large cell lymphoma (DLCL) (n = 15), acute myeloid leukemia (AML) (n = 11), mantle cell lymphoma (n = 6), follicular lymphoma (FL) (n = 5), Hodgkin's disease (HD) (n = 8) and chronic lymphocytic leukemia (CLL) (n = 5) - were analyzed. Parameters of cellular and humoral immunity, including CBC, FACS analysis of lymphocyte subpopulations, cytokines sIL2-R, IL-6, IL-10, TNF-a, serum complement components C3, C4, CH50 and total concentrations of serum immunoglobulin IgG, IgM, IgA were measured. At diagnosis patients with AML had severe cellular immunodeficiency (neutro-, monocyte- and lymphopenia). Infectious complications occurred in 8 of 11 AML patients (73%). Patients with DLCL and MCL had predominantly increased CD3+/CD8+ lymphocyte subsets (median 0,26/m l) with an infection rate from 30%. However, the rate was significantly higher if CD4+ depletion (43%) or CD19+ depletion (40%) were additionally present. High IL-2, IL-6, IL-10 and TNF-a levels were mostly observed in FL and MCL. Elevated TNF-a levels were also associated with infections (43%) and advanced stage or B-symptoms. IL-10 was found to correlate with mortality and relapse risk in all patients (overall: 18% and 20% respectively, increased IL 10 level: 39% and 33% respectively). Serum complement levels were normal to slightly elevated in all patients. Very high levels (CH50 > 160) were found in patients with Hodgkin's disease (5/8 patients, 63%) and decreased immunoglobulin levels occurred in CLL patients only, none of whom had infections during follow up. These results indicate that untreated patients with DLCL and MCL have a significant lower CD8+T-lymphocyte cell count. In contrast to previous studies we did not found a predominant depletion of CD4+T-lymphocyte. A combination of CD4+/CD8+ T-cell deficiency or T-/B-cell deficiency was strongly associated with infections, thus antibiotic prophylaxis seems warranted in this patient group. Additionally IL-10 may serve as prognostic marker particularly in MCL and FL.