EFFECT OF TREATMENT ON THE PROGNOSTIC VALUE OF S-PHASE FRACTION IN NON-HODGKINS-LYMPHOMA

Purpose: To investigate the prognostic value of cell proliferation rat e in non-Hodgkin's lymphoma, study its association with histologic cla ssification, and investigate whether its predictive value is influence d by the type of treatment given. Patients and Methods: The S-phase fr action (SPF) size was determined by DNA flow cytometry from paraffin-e mbedded tissue obtained at diagnosis from 490 patients with non-Hodgki n'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 hi stologic grading performed either according to the Working Formulation or Kiel classification (P < .0001 for both). The mean SPFs of low-, i ntermediate-, and high-grade malignant lymphomas were 4.9% (95% confid ence 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 lo wer than the median (7.9%) had a 58% 5-year and 44% 15-year survival r ate, 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 significa ntly associated with prognosis in some subgroups, such as among patien ts treated primarily with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 114) or cycloptrosphamide, vincristine, and prednisone (COP) (n = 124) with or without radiotherapy (P > .05), wh ereas a stronger association was found among patients with stage I or If lymphoma treated with radiotherapy only (n = 100; P = .003) and amo ng patients with stage III or IV lymphoma who did not receive chemothe rapy (n = 44; P < .0001). In multivariate analyses chat included the f actors used to construct the international Prognostic index, SPF had i ndependent prognostic value both in few-grade and intermediate- or hig h-grade lymphomas, hut not in the subset of patients treated with comb ination chemotherapy with or without radiotherapy. Conclusion: Cell pr oliferation 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 valu e of SPF. (C) 1994 by American Society of Clinical Oncology.