Clinical significance of the WHO grades of follicular lymphoma in a population-based cohort of 505 patients with long follow-up times

The prognostic value of grading follicular lymphoma has been debated since the 1980s. There is consensus that World Health Organization (WHO) grades 1 and 2 are indolent, but not whether grades 3A or 3B are aggressive. We retrospectively reviewed the follicular lymphoma diagnoses according to the 2008 WHO classification in all diagnostic specimens from a population-based cohort of 505 patients with a median follow-up time of 10.0 years (range, 4.616.0). After excluding 43 patients with concomitant diffuse large B-cell lymphoma, 345 remained with grade 12, 94 with grade 3A, and 23 with grade 3B follicular lymphoma. Grades 12 and 3A seemed equally indolent, with indistinguishable clinical courses, even in patients receiving anthracyclines. Compared with grades 13A and independently of clinical factors, grade 3B correlated with higher mortality (P = 0.008), but outcome was improved after upfront anthracycline-containing therapy (P = 0.015). In contrast to grade 13A patients, grade 3B patients experienced no relapses or deaths beyond 5 years of follow-up. Furthermore, patients with grade 3B were predominantly male and seldom presented with bone-marrow involvement. We conclude that follicular lymphoma grade 13A is indolent and incurable with conventional therapy. Grade 3B appears to be an aggressive but curable disease.