Classification of patients with T-cell chronic lymphocytic leukemia and expansions of granular lymphocytes: heterogeneity of Italian cases by a multiparameter analysis.

The peripheral blood mononuclear cells (PBMC) from 750 Italian patients with chronic lymphocytic leukemia (CLL) were evaluated in order to detect cases with T-cell expansions. The PBMC of 18 patients (2.4%) were found to be capable of rosetting with sheep red blood cells. Further characterization of these cells with a panel of monoclonal antibodies and other immunological and cytochemical tests led us to tentatively subdivide these 18 patients into three groups. The first one included 6 patients whose cells expressed a T-helper phenotype: they exhibited frequent skin involvement and an aggressive clinical course, and some of the patients in this group demonstrated chromosome abnormalities. On the other hand, group 2 (10 cases with expansions of granular lymphocytes and/or T suppressor-bearing phenotype cells) usually presented with a mild clinical course. These cases did not generally require therapy and a diagnosis of leukemia could not be unequivocally confirmed. Cells from the two remaining patients displayed both B-cell markers and E-rosetting ability, thus belonging to the rare group of false T-cell CLL. In fact, the clinical course and management of the latter cases were similar to those of classical B-CLL disease. In the first and second groups, mechanisms reported to be involved in mature T-cell proliferations (response to interleukin-2, production of interleukin-2 or interferon) were investigated, but the cells under study displayed neither growth ability nor lymphokine production in the above assays. In addition, these cells were negative with the anti-Tac monoclonal antibody that appears to recognize the receptor for interleukin-2. More importantly, none of these patients had serum antibodies to the recently described human T-cell leukemia/lymphoma virus (HTLV), possibly responsible for Japanese and West Indian adult T-cell leukemia (ATL) and for sporadic cases of ATL observed in other countries. Taken together, our results outline some differences between European and ATL patients. Furthermore, the data presented point out the heterogeneity of the disease and emphasize that an immunological classification and, in particular, the detection of a helper phenotype have relevant prognostic and therapeutical importance.