Adverse effects of activated cytotoxic T lymphocytes on the clinical outcome of nodal anaplastic large cell lymphoma

Systemic (nodal) anaplastic large cell lymphoma (ALCL) is a subgroup of T-c ell non-Hodgkin's lymphomas with a relatively favorable clinical outcome. P art of systemic ALCLs harbor a genetic aberration (usually the t(2;5)(p23;q 35) translocation) containing the anaplastic lymphoma kinase (ALK) gene at 2p23, which results in aberrant expression of the ALK. protein. Recently, w e have shown that the presence of high percentages of activated cytotoxic T lymphocytes (CTLs) in tumor biopsy specimens of Hodgkin's disease (HD) is associated with a poor prognosis. In the present study, we investigated the prognostic value of percentages of: activated CTLs in combination with ALK expression in primary nodal ALCL. Primary nodal biopsies of 42 patients wi th ALCL were investigated for the percentage of activated CTLs (quantified using Q-PRODIT) and the expression of ALK by immunohistochemistry using mon oclonal antibodies (MoAbs) directed against T-cell antigen granzyme B (GrB) and ALK, respectively. These parameters were evaluated for their predictiv e value regarding progression-free and overall survival time. The presence of a high percentage of activated CTLs (ie, greater than or equal to 15%) w as found to be an unfavorable prognostic marker. In combination with a lack of ALK expression, it was possible to identify a group of patients with a very poor prognosis. In this group, 13 of 16 patients died within 2 years a s a result of the disease. Of the remaining 26 patients, only three (all AL K negative) died (P < .0001). Furthermore, the percentage of activated CTLs combined with ALK status appeared to be of stronger prognostic value than the International Prognostic Index (IPI). We conclude that a high percentag e of activated CTLs present in biopsy material of patients with primary nod al ALCL is a strong indicator for an unfavorable clinical outcome. The comb ination of ALK expression and percentage of activated CTLs appears to be mo re sensitive than the IPI in identifying a group of patients with a highly unfavorable clinical outcome who may be eligible for alternative (high dose ) therapy schemes. (C) 1999 by The American Society of Hematology.