S‐phase fraction by the labeling index as a predictive factor for progression and survival in low grade non‐Hodgkin's lymphoma

Background. The purpose of this study was to learn if the bromodeoxyuridine labeling index (LI), a measure of the S‐phase fraction, is an independent prognostic factor for overall survival (OS) for patients with newly diagnosed low grade non‐Hodgkin's lymphoma (NHL). In addition, the ability of the LI to predict time to progression (TTP) in a group of patients observed without therapy after initial diagnosis was determined. Methods. Patients eligible for this study had biopsy proven low grade NHL, adequate tissue to perform the LI, and were previously untreated. The bromodeoxyuridine LI was performed on fresh biopsy samples using a slide‐based immunofluorescence procedure. Results. One‐hundred twelve patients were followed prospectively for OS, and 50 of these patients who initially were observed without therapy were eligible for an analysis of TTP. The LI (≤1% vs. >1%) and presence of “B” symptoms were significant univariate prognostic factors for survival (P values of 0.004 and <0.001, respectively). In a multivariate analysis, the LI and symptoms retained independent prognostic significance, whereas disease stage, histologic subtype, and age did not. In the group who were observed after diagnosis, the LI was not an independent predictor of TTP. Conclusions. The LI at initial diagnosis is an independent prognostic factor for OS of patients with low grade NHL, but it does not help choose patients for observation without therapy. Measurements of the LI should be considered as part of the on‐study evaluation of patients entering cooperative group trials evaluating new therapies for this group of lymphomas. Cancer 1995;76:1059–64.