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  • Patients with early-stage follicular lymphoma (FL) can experience prolonged remissions with radiation therapy, particularly in the presence of stage I disease and lesions smaller than 3 cm; as such, surveillance should be reserved only to patients who are not candidates for radiation.

  • High tumor burden in patients with FL is defined by the presence of one or more Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria; these include: significant lymphadenopathies (one >7 cm or three each >3 cm), splenomegaly, impending organ compromise, pleural effusion, elevated circulating lymphoma cells, and cytopenia. Among patients with advanced-stage FL, those with high tumor burden should be considered for active treatment; in the presence of low tumor burden, observation or single-agent rituximab are potential management strategies.

  • Both chemoimmunotherapy and immunotherapy (with lenalidomide) are potential treatment options for patients with advanced-stage, high tumor burden FL; pretreatment positron emission tomography–computed tomography (PET-CT) scan may identify patients who would benefit from an anthracycline-based regimen.

  • PET-CT scan performed at the end of chemoimmunotherapy is considered prognostic. Response to frontline therapy may inform pursuit of maintenance therapy given retrospective data suggesting the largest impact of maintenance rituximab observed among those achieving a partial response to frontline chemoimmunotherapy.

  • Patients with FL who progress within 24 months from the initiation of frontline chemoimmunotherapy may have a shorter overall survival; these patients should be evaluated for clinical trials with novel agents or cellular therapy


Follicular lymphoma (FL) is a neoplasm composed of centrocytes and centroblasts that are derived from the germinal center of lymphoid follicles.1 Most cases of FL have a diffuse pattern but these neoplasms rarely have an entirely diffuse pattern. Being derived from germinal center B cells, these neoplasms commonly express CD10, Bcl-6, HGAL, and LMO2 and carry t14;18(q32;q21).

Importantly, knowledge of FL has increasing led to the recognition of variants of FL (e.g. in situ follicular neoplasia) as well as distinct types of FL, the latter including primary cutaneous follicle center cell lymphoma, pediatric-type follicular lymphoma, and follicular lymphoma with IRF4 rearrangement.

In this chapter we focus on the common form of FL that represents about 80-85% of all cases of FL.


FL, the second most commonly occurring lymphoma in the United States, represents 22% of all B-cell non-Hodgkin lymphomas (NHLs)2 and 80% of all indolent B-cell lymphomas. FL occurs almost exclusively in adults, with an equal frequency in men and women. The incidence rates are highest among Caucasians, and median age at diagnosis is approximately 63 years.3 In the United States, from 2012-2016, the number of new cases of FL was 2.7 per 100,000 men and women per year after age-adjustment. The number of deaths was 0.5 per 100,000 men and women per year.4 Risk of FL increased in persons who have a first-degree relative with NHL or who worked as a spray painter and ...

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