Positive Direct Antiglobulin Test (DAT) in Chronic Lymphocytic Leukemia (CLL) Patients: Correlation with Prognostic Factors.

although the clinical course of patients with B-cell chronic lymphocytic leukemia (CLL) is often complicated by autoimmune phenomena few data are available concerning the prevalence of autoimmune diseases in this lymphoprolipherative disorder as well as their clinical outcome. Autoimmune hemolytic anemia (AIHA) is the most common form, occurring in 10% to 25% of patients during CLL course. DAT may be positive at some time during the course of the disease in up to 35% of cases, but overt AIHA occurs less frequently. Although AIHA may occur in asymptomatic untreated CLL, it is more common in patients with advanced-stage disease. So far it is unknown if also the biological characteristics of CLL may have any influence on the risk of developing autoimmune phenomena. Recently, an exceedingly high prevalence of un-mutated IgVH, with an excess of VH1 and VH3 families has been described in patients with autoimmune thrombocytopenia and DAT status has been correlated with clinical and laboratory prognostic factors in CLL Chinese population.

the current retrospective study was conducted to investigate the relation between incidence of positive DAT test and biological features of CLL patients.

in our institution 158 patients with CLL were studied with DAT at some time during the disease course. Characteristics of patients are summarized in the table. DAT resulted positive in 42 patients (26.6%), overt AIHA occurred in 28,6% of them. Univariate analysis by Fisher's exact test was performed to establish the association between DAT result and AIHA development with the following variables: age, sex, Binet stage, LDH and beta2 microglobulin (B2m) at diagnosis, IgVH status, VH families, ZAP70, CD38 and FISH analysis.

the incidence of positive DAT was significantly increased in presence of higher B2m (p 0.011) and highly correlated with IgVH un-mutated status (p 0.014). No prevalence or correlation for the IgVH families was recorded between DAT positive and negative patients. In the subgroup of patients with poor risk FISH chromosome aberration (deletion in 17p13, 11q22 or 6q21) we found a trend (p 0.064) for higher frequency of positive DAT compared to good risk (deletion in 13q14 or trisomy 12). A trend for increased positivity of DAT has been also found in patients with positive ZAP70 (p 0.083) and increased LDH value at diagnosis (p 0.051). Among DAT-positive patients none of biological and clinical characteristics listened above showed a significant correlation with the risk to develop AIHA.

in our series DAT positivity correlated with poor risk biological features, however no difference was detected in terms of OS between patients with positive or negative test. Furthermore, we could speculate that patients with un-mutated IgVH status are characterized by a peculiar antibody reactivity, resulting in a major failure controlling the emergence of auto-antibodies from normal B cells.

Although the results of this study warrant further confirmation from larger series, the documented association of poor biological features and DAT positivity in CLL patients, suggests that this laboratory test may improve prognostic evaluation at diagnosis.

No relevant conflicts of interest to declare.