Percentage of activated cytotoxic T-lymphocytes in anaplastic large cell lymphoma and Hodgkin's disease: an independent biological prognostic marker

Recently, we demonstrated that the presence of high percentages of activate d cytotoxic T-lymphocytes (CTLs) in biopsy specimens of both Hodgkin's dise ase (HD) and ALK negative anaplastic large cell lymphoma (ALCL) is associat ed with a poor prognosis. To test whether this biological prognostic factor is more important in predicting clinical outcome than histological diagnos is or clinical factors, we compared the prognostic value of these parameter s in an expanded group of classical HD and ALK negative ALCL. Tumor biopsie s of classical HD (n=83) and ALK negative systemic nodal ALCL (n=43) were i nvestigated for the presence of activated CTLs by immunohistochemistry, usi ng a monoclonal antibody directed against granzyme B. Percentages of activa ted CTLs were quantified using Q-PRODIT, and their prognostic value was com pared to that of histological diagnosis and clinical parameters, including age and stage. Both in classical HD and ALK negative ALCL, a high percentag e of activated CTLs (ie greater than or equal to 15%) identified a group of patients with poor overall and progression-tree survival time, even when a djusted for stage. In multivariate analysis, percentage of activated CTLs r emained a strong independent prognostic marker, and was more sensitive than histological diagnosis or clinical factors in predicting overall survival time. We conclude that a high percentage of activated CTLs in the reactive infiltrate of ALK negative ALCL and classical HD is a strong indicator for an unfavorable clinical outcome, regardless of histological diagnosis or cl inical parameters. As such, this biological parameter may be an especially helpful tool to determine therapeutic strategies in cases in which the diff erentiation between ALK negative ALCL and HD remains difficult.