Eleven patients with mature or peripheral T-cell lymphoma (PTL), other than mycosis fungoides, were identified using an extensive battery of T- and B-cell markers. Eight cases had a histologic diagnosis of either diffuse large cell or mixed lymphoma, three of small cell type. All cases had one or more "mature" T-antigens and an absence of B- and immature T-antigens. Assessment of T-antigens included E-rosettes (Er), anti-Leu 1-7 and Tdt. The authors delineated striking heterogeneity of T-antigen expression: 9 different immunotypes in 11 cases. Subset T-antigen assessment indicated T-helper neoplastic cells in five cases and T-suppressor in two. The remaining four had universal T-antigens alone. Seven cases appeared to have "novel" T-phenotypes not corresponding to normal T-ontogeny phenotypes. Novel or idiosyncratic phenotypes may be a key characteristic of PTL. Since no single T-antigen, including Er and Er receptor (Leu-5), was expressed in all cases, a battery of monoclonal antibodies is necessary to detect PTL. Clinically, the authors found PTL unexpectedly aggressive, despite mature immunotype. Most patients were elderly (median age 69); all had extranodal disease with cutaneous involvement (six cases) most frequent. Responses to chemotherapy frequently proved transient, with median survival of nine months. A fulminant course was noted even with localized presentation. Clinical outcome suggests PTL requires new therapeutic strategies.

The prognostic importance of immunobiologic factors in diffuse large-cell lymphoma (DLCL) is studied in 105 consecutive DLCL patients. Multivariate results using the Cox proportional hazards model clearly indicate that the Ki-67 index (P = .002), a marker of cell proliferation activity, and the presence or absence of human leukocyte antigen-DR (HLA-DR) (P = .007) are strong predictors of survival even in the presence of established clinical factors of stage (P = .015) and symptoms (P = .050). Using these four variables, prognostic groups were formed identifying patient groups with varying degrees of risk. The group of patients with three or four risk factors present at the time of diagnosis had a median survival of 4 months compared with a median survival of 59 months for the group with no risk factors. Similarly, prognostic groups for disease-free survival (DFS) were constructed based on the proportional hazards model that involved B versus T phenotype (P = .035) and HLA-DR (P = .054). Median DFS for the patient group with one or two risk factors present was 11 months compared with 43 months with no risk factors present. This study suggests immunobiologic parameters are important predictors of clinical outcome in DLCL patients and are of value in identifying subgroups of patients who have not responded to currently available therapy. The practical significance of this study is to identify parameters that may suggest specific changes in therapy of patient subgroups.

To assess the prognostic significance of the growth fraction in diffuse large cell lymphoma (DLCL), we studied 105 DLCL patients with the monoclonal antibody Ki-67 applied to frozen tissue sections. Ki-67 detects a nuclear antigen associated with cell proliferation not found in resting cells. Ki-67 findings and other clinical prognostic factors were correlated with outcome using univariate and multivariate analyses in the proportional hazards model. High proliferative activity, defined as nuclear Ki-67 expression in greater than 60% of malignant cells (Ki- 67 greater than 60), was found to be a strong predictor of poor survival among these patients (P = .003, log-rank). The 19 patients with Ki-67 greater than 60% had a median survival of 8 months compared with a median survival of 39 months for the 86 patients with Ki-67 less than or equal to 60%. Examination of pretreatment clinical variables indicated the patient groups were similar with regard to age, sex, stage, B symptoms, tumor bulk, and lactate dehydrogenase (LDH). Both patient groups received comparable curative intent therapy and showed comparable complete response rate precluding treatment differences as modifying outcome. Multivariate analysis indicated Ki-67 is an independent predictor of survival (multivariate P = .006). Further statistical analysis using only B-cell DLCL patients treated with CHOP (63 patients) indicated that Ki-67 greater than 60 retained strong prediction of poor outcome (P = .002, log-rank) among this homogeneous group. We conclude that high proliferative activity (Ki-67 greater than 60) is an independent factor allowing laboratory prediction of probable poor outcome of DLCL.

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