Follicular Non-Hodgkin Lymphoma Grade 3a and 3b Subtypes Exhibit Similar Clinical Behaviour and Treatment Outcome

Abstract

The clinical usefulness of separating follicular lymphoma (FL) grade 3 into FL grade 3A (FL3a) and 3B (FL3b) subtypes remains controversial. The relative aggressiveness of these two subtypes and their potential curability with anthracycline-based therapy continues to be debated. Discrepancies in the literature may be related to the relatively small number of patients in most series and to the variable inclusion of patients with a diffuse histologic component on biopsy, likely representing early transformation. We present a retrospective review of clinical characteristics and outcome in a large cohort of patients with FL3a and FL3b, as strictly defined by WHO diagnostic criteria.Patients Patients diagnosed with FL grade 3 in the province of British Columbia (BC) between the years 1982 and 2008 were identified through the BC Cancer Agency Lymphoid Cancer Database. A total of 161 patients with pathology available for central review were included for analysis, and were categorized as FL3a (n=139) or FL3b (n=22) using current WHO criteria. Cases containing a diffuse component on biopsy were excluded.Results Median age of the entire cohort was 63 years (range, 18–88). There were no significant differences in age, sex, stage, serum LDH levels, or number of extranodal sites between the subgroups. However, there was a trend toward worse performance status in patients with FL3b compared with FL3a (PS 2–4 27% vs. 12%, respectively; p=0.054). Overall, more patients in the FL3b subgroup had a high-intermediate or high-risk IPI score compared with patients in the FL3a subgroup (36% vs. 17%, p=0.028). A significantly higher number of patients with FL3b received an anthracycline-based regimen as front-line therapy (82% vs. 36%, p <0.001) and approximately one third of the entire cohort received rituximab. With a median follow-up of 38 months (range, 1–224), no difference in overall survival (OS) (p=0.79) or disease-specific survival (DSS) (p=0.38) was observed between FL3a and FL3b patients (see Figure below) (5-year OS, 72% vs. 70% and 5-year DSS, 77% vs. 70%, respectively). Analysis limited to the FL3a subgroup showed no OS advantage for patients who received an anthracycline-containing regimen as initial therapy compared with those who did not (p=0.24).Conclusions Overall no significant differences in clinical outcome were noted between patients with FL3a and FL3b. No plateau in the survival curves was seen, suggesting that neither subtype is curable even with the use of anthracycline-based therapy. This large retrospective analysis, which expands on an earlier cohort from the province of British Columbia, calls into question the clinical relevance of this histological grading designation. [Display omitted]