Results from a retrospective study of patients with low-stage (ie, stage I-II) follicular lymphoma, published in Leukemia & Lymphoma, showed that patients with grade 3 disease can experience favorable outcomes similar to those observed for patients with grade 1 or grade 2 disease.

Follicular lymphoma, a B-cell lymphoma, is a heterogeneous disease that is classified as grade 1, grade 2, grade 3A, or grade 3B according to the proportion of centroblasts (and centrocytes, in the case of grade 3A) in neoblastic follicles. Because most low-stage follicular lymphoma is grade 1 or grade 2 disease, and grade 3 follicular lymphoma is more common in advanced disease, there is a dearth of evidence to direct optimal treatment in patients with low-stage, grade 3 follicular lymphoma.

A retrospective chart review of the clinicopathologic characteristics, treatment approaches, and clinical outcomes of patients diagnosed with low-stage follicular lymphoma at MD Anderson between 2003 and 2013 was performed. The primary end point of the study was progression-free survival (PFS), with secondary end points including distant failure-free survival (DFFS), local recurrence-free survival (LRFS), and overall survival (OS).

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Of the 190 consecutive patients identified as having stage I to stage II follicular lymphoma, 52 had grade 3 disease, although only 7 of these had grade 3B disease; of the 138 patients with grade 1-2 disease, 6 were lost to follow-up.

Regarding patient and disease characteristics in the 2 groups, including primary site of disease, disease stage, median Ki-67, and Follicular Lymphoma International Prognostic Index (FLIPI)-2 score among other characteristics, the only significant difference was a higher percentage of patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 in the group with grade 3 disease.

Treatment approaches in the group of patients with grade 3 follicular lymphoma were varied, and included no treatment (5.8%), radiation therapy alone (11.5%), rituximab-based systemic therapy alone (40.4%), or a combination of rituximab-based systemic and radiation therapy (42.3%).

At a median follow-up of 65 months, the 5- and 10-year of rates of PFS for the group of patients with grade 3 disease were 76.1% and 71.8%, respectively.  Five- and 10-year rates of OS were 87.6% and 83.9%, respectively.

Interestingly, no patients with grade 3 disease treated with radiation therapy experienced a local recurrence of disease. However, 50% of patients treated with radiation therapy alone experienced a distant relapse.

A comparison of patients with grade 3 disease treated with radiation alone or systemic therapy followed by radiation therapy showed significantly better PFS (P =.003) and DFFS (P =.004) in the latter group, but no significant difference in OS (P =.476) or LRFS (P =.476).

For the group of patients with stage I to stage II follicular lymphoma undergoing active treatment, a comparison of outcomes in the grade 1, grade 2, and grade 3 cohorts did not reveal significant differences in PFS (P =.493) or OS (P =.330), although more patients with grade 3 disease received combined modality therapy.

They concluded that “further studies are warranted to assess the outcomes of patients treated with combined modality [therapy], determine the optimal systemic therapy and delineate subgroups that would benefit from more aggressive management.”


  1. Ayoub Z, Andraos T, Milgrom SA, et al. Limited stage grade 3 follicular lymphoma patients can experience favorable outcomes with combined modality therapy [published April 3, 2019]. Leuk Lymphoma. doi: 10.1080/10428194.2019.1597081