Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype

Anaplastic large cell lymphoma (ALCL) is a distinct entity of non-Hodgkin lymphoma, characterized by a proliferation of pleomorphic large lymphoid cells that express CD30. Recent studies have found that a subset of ALCL aberrantly expresses a chimeric anaplastic lymphoma kinase (ALK) protein as a result of t(2; 5)(p23;q35) or variant translocations. ALK-positive ALCLs feature good prognosis, but some of them lead to poor outcomes. Since CD56 is expressed in some ALCLs, its clinical significance was examined in a series of T/null cell type ALCLs. Of 143 patients, 83 (58%) showed ALK-positive staining, and of 140 patients, 25 (18%) expressed CD56. The ALK-positive subgroup was characterized by a younger age of onset (P < .0001), lower serum lactate dehydrogenase level (P = .01), better performance status (P = .03), less frequent extranodal involvement (P = .01), lower international prognostic index (IPI) categories (P = .002), and superior survival (P = .0009) in comparison with the ALK-negative group, suggesting that ALK is a specific marker defining a distinct subtype. CD56⁺ cases showed a significantly poor prognosis overall (P = .002) as well as in both ALK-positive and ALK-negative subgroups (P = .02 and P = .04, respectively). Multivariate analysis confirmed that CD56 is independent of other prognostic factors, including IPI. Although CD56⁺ cases showed a higher incidence of bone involvement, no other differences in clinicopathologic parameters were found between the CD56⁺ and CD56^- groups. These findings suggest that CD56 is not a marker to identify a distinct subtype of ALCL, but a strong clinical prognostic factor. Effective therapeutic approaches should be explored for high-risk ALCL patients, who can be identified by means of a prognostic model, including CD56. (C) 2000 by The American Society of Hematology.