Effect of treatment on the prognostic value of S-phase fraction in non-Hodgkin's lymphoma.

Abstract

PURPOSE To investigate the prognostic value of cell proliferation rate in non-Hodgkin's lymphoma, study its association with histologic classification, and investigate whether its predictive value is influenced by the type of treatment given. PATIENTS AND METHODS The S-phase fraction (SPF) size was determined by DNA flow cytometry from paraffin-embedded tissue obtained at diagnosis from 490 patients with non-Hodgkin's lymphoma, diagnosed in a defined geographic area from 1970 to 1991. Clinical data were collected from hospital records and the files of the Finnish Cancer Registry. RESULTS SPF size correlated well with histologic grading performed either according to the Working Formulation or Kiel classification (P < .0001 for both). The mean SPFs of low-, intermediate-, and high-grade malignant lymphomas were 4.9% (95% confidence interval [CI], 4.2% to 5.5%), 10.3% (95% CI, 9.3% to 11.4%), and 15.5% (95% CI, 14.0% to 16.9%), respectively. Lymphomas with an SPF lower than the median (7.9%) had a 58% 5-year and 44% 15-year survival rate, whereas those with an SPF larger than the median had a 44% 5-year and 40% 15-year survival rate (P < .0001). SPF size was not significantly associated with prognosis in some subgroups, such as among patients treated primarily with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 114) or cyclophosphamide, vincristine, and prednisone (COP) (n = 124) with or without radiotherapy (P > .05), whereas a stronger association was found among patients with stage I or II lymphoma treated with radiotherapy only (n = 100; P = .003) and among patients with stage III or IV lymphoma who did not receive chemotherapy (n = 44; P < .0001). In multivariate analyses that included the factors used to construct the International Prognostic Index, SPF had independent prognostic value both in low-grade and intermediate- or high-grade lymphomas, but not in the subset of patients treated with combination chemotherapy with or without radiotherapy. CONCLUSION Cell proliferation rate measured as SPF is closely associated with histologic grading in non-Hodgkin's lymphoma, and it has independent prognostic value. The treatment given influences considerably the prognostic value of SPF.