ACTIVATED CYTOTOXIC T-CELLS AS PROGNOSTIC MARKER IN HODGKINS-DISEASE

Although the results of treatment of Hodgkin's disease (HD) have impro ved considerably in the last decades, the disease remains fatal in a m inority of patients. We have recently shown that numbers of activated cytotoxic T cells (CTLs), present in tumor biopsy specimens, differ co nsiderably among individual HD patients, Because CTLs are the major ef fector cells in elimination of neoplastic cells, we investigated wheth er the number of activated CTLs is related to the clinical outcome of the individual patient with HD. Activated CTLs present in tumor biopsy specimens of patients with nodular sclerosis or mixed cellularity HD were identified by immunohistochemistry using an antibody directed aga inst granzyme B (GrB), a major constituent of the cytotoxic granules o f activated CTLs and natural killer cells, and an antibody directed ag ainst CD8. The presence of a high percentage of GrB(+) lymphocytes was found to be an unfavorable prognostic marker. The large majority of G rB(+) cells were also CD8(+), indicating that these cells are activate d CTLs. Prognosis was found to decrease with increasing percentages of GrB(+) lymphocytes. Optimal discrimination between patients with good and poor prognosis was obtained when the threshold was set at 15% GrB (+) cells; 6 of 10 patients with greater than or equal to 15% GrB(+) l ymphocytes died as a result of the disease, as compared with 6 of 70 p atients with less than 15% GrB(+) lymphocytes (P <.0001). In stage-2 p atients, the percentage of GrB(+) lymphocytes retained its predictive value in a multivariate analysis including histology, sex, age, erythr ocyte sedimentation rate, and the presence of B symptoms as covariable s. In addition, patients with greater than or equal to 15% GrB(+) lymp hocytes had a shortened progression-free survival time (P =.002). We c onclude that a high percentage of activated CTLs present in biopsy mat erial of HD patients is a strong indicator for an unfavorable clinical outcome. (C) 1997 by The American Society of Hematology.