ZAP-70 EXPRESSION IS ASSOCIATED WITH INCREASED RISK OF AUTOIMMUNE CYTOPENIAS IN CLL PATIENTS

Roberta Zanotti (1) , Francesco Frattini (1) , Paolo Ghia (2) , Carlo Visco (3) , Alberto Zamò (4) , Omar Perbellini (1) , Stefania Stella (5) , Monica Facco (6) , Ilaria Giaretta (3) , Marco Chilosi (4) , Giovanni Pizzolo (7) , Achille Ambrosetti (8)

1 Department of Clinical and Experimental Medicine
2 Department of Oncology
3 Department of Hematology
4 Department of Pathology
5 Institute for Cancer Research and Treatment
6 Department of Hematology
7 UNIVR - Università degli studi di Verona = University of Verona
8 Dipartimento Medicina Clinica e Sperimentale

Autoimmune cytopenias (AIC) are frequent in 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 males, median age 63 years, 77.9% Binet stage A, 17.6% B and 4.5% C. AIC occurred in 46 patients (16%): 31 autoimmune haemolytic anaemias, 10 autoimmune thrombocytopenias, 4 Evans syndromes and 1 pure red cell aplasia. Of the 46 cases of AIC, 37 (80%) occurred in ZAP-70positive patients and 9 (20%) in ZAP-70negatives. ZAP-70 expression (HR=7.42; 95%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 for ZAP-70 expression and IGHV status the occurrence of AIC was higher in ZAP-70positive/IGHVunmutated cases (35%) than in patients ZAP-70negative/IGHVmutated (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-70positive CLL, particularly when IGHVunmutated, should be considered in the clinical management.

Mots clés: Medicine

Roberta Zanotti, Francesco Frattini, Paolo Ghia, Carlo Visco, Alberto Zamò, et al.. ZAP-70 EXPRESSION IS ASSOCIATED WITH INCREASED RISK OF AUTOIMMUNE CYTOPENIAS IN CLL PATIENTS. American Journal of Hematology, 2010, 85 (7), pp.494. ⟨10.1002/ajh.21737⟩. ⟨hal-00552327⟩