Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma

Anaplastic large cell lymphoma (ALCL) is an aggressive lymphoma that is fre quently associated with the t(2;5)(p23; q35), resulting in expression of a fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which c an be detected by either monoclonal or polyclonal antibodies to the ALK pro tein. The clinical features of adults with ALCL are incompletely described, and the prognostic factors that are useful for predicting survival remain unclear. This report describes the clinical and laboratory findings in 70 a dults with systemic ALCL who were treated with curative intent. We attempte d to identify the clinical and pathological factors of prognostic importanc e, including the International Prognostic Index (IPI), immunophenotype, and expression of the ALK protein. The median age of the patients was 49 years (range, 15 to 75). There were 26 women and 44 men with a median follow-up of 50 months for living patients. Advanced stage was present in 56% and B s ymptoms were noted in 70% of the patients. Immunostains showed that 46% of the cases had a T-cell phenotype, 36% a null phenotype, and 18% a B-cell ph enotype. The expression of ALK protein was found in 51% of the cases. The I PI factors were evenly distributed between the ALK(+) and ALK(-) groups, ex cept that the ALK(+) patients were younger (median age, 30 v 61 years; P < .002). The ALK(+) cohort included cases with null (44%), T-cell (42%), and B-cell (14%) phenotypes. All 10 cases with cytogenetic or molecular evidenc e of a t(2;5) were ALK(+). The 5-year overall survival (OS) of the entire c ohort was 65%. The B-year OS of the ALK(+) and ALK(-) cases was 79% and 46% , respectively (P < .0003). Analysis of only the T-cell/null cases (n = 57) showed a 5-year OS of 93% for the ALK(+) cases and only 37% for the ALK- c ases (P < .00001). Univariate analysis of the clinical features showed that age less than or equal to 60 years (P < .007), a normal serum lactate dehy drogenase (LDH) (P < .00001), a good performance status (Eastern Cooperativ e Oncology Group [ECOG] <2) (P < .03), less than or equal to 1 extranodal s ite of disease (P < .012), and an IPI score less than or equal to 3 (P < .0 0001) were associated with improved OS. Although a younger age correlated w ith ALK positivity, multivariate analysis showed that only a normal serum L DH (P <.00001), an IPI score of less than or equal to 3 (P < .0005), and AL K protein expression (P < .005) predicted independently for an improved OS. We conclude that ALCL is a heterogeneous disorder. However, ALK protein ex pression is an independent predictor of survival and serves as a useful bio logic marker of a specific disease entity within the spectrum of ALCL. (C) 1999 by The American Society of Hematology.