title: ZAP-70 expression is associated with increased risk of autoimmune cytopenias in CLL patients.
abstract: Autoimmune cytopenias (AIC) are frequent in chronic lymphocytic leukemia (CLL) patients, but risk factors and prognostic relevance of these events are controversial. Data about the influence on AIC of biological prognostic markers, as ZAP-70, are scanty. We retrospectively evaluated AIC in 290 CLL patients tested for ZAP-70 expression by immunohistochemistry on bone marrow biopsy at presentation. They were 185 men, median age 63 years, 77.9% Binet stage A, 17.6% B and 4.5% C. AIC occurred in 46 patients (16%): 31 autoimmune hemolytic anemias, 10 autoimmune thrombocytopenias, four Evans syndromes, and one pure red cell aplasia. Of the 46 cases of AIC, 37 (80%) occurred in ZAP-70 positive patients and nine (20%) in ZAP-70 negatives. ZAP-70 expression [Hazard Ratio (HR) = 7.42; 95% confidence interval (CI): 2.49-22.05] and age >65 years (HR = 5.41; 95% CI: 1.67-17.49) resulted independent risk factors for AIC. Among the 136 patients evaluated both for ZAP-70 expression and IGHV status, the occurrence of AIC was higher in ZAP-70 positive/IGHV unmutated cases (35%) than in patients ZAP-70 negative/IGHV mutated (6%) or discordant for the two parameters (4%; P < 0.0001). In ZAP-70 positive patients, occurrence of AIC negatively influenced survival (HR = 1.75; 95% CI: 1.06-2.86). The high risk of developing AIC in ZAP-70 positive CLL, particularly when IGHV unmutated, should be considered in the clinical management.
authors.affiliation: Department of Medicine, University of Verona, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Zanotti
authors.forename: Franzesco
authors.initials: F
authors.lastname: Frattini
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
authors.forename: Alberto
authors.initials: A
authors.lastname: Zamò
authors.forename: Omar
authors.initials: O
authors.lastname: Perbellini
authors.forename: Stefania
authors.initials: S
authors.lastname: Stella
authors.forename: Monica
authors.initials: M
authors.lastname: Facco
authors.forename: Ilaria
authors.initials: I
authors.lastname: Giaretta
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pizzolo
authors.forename: Achille
authors.initials: A
authors.lastname: Ambrosetti
mesh_terms: D000744:Anemia, Hemolytic, Autoimmune; D001327:Autoimmune Diseases / Q000097:blood / Q000209:etiology*; D014408:Biomarkers, Tumor; D006402:Hematologic Diseases / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016553:Purpura, Thrombocytopenic, Idiopathic; D012010:Red-Cell Aplasia, Pure; D012189:Retrospective Studies; D012307:Risk Factors; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human