Disease overview: Follicular lymphoma (FL) is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Follicular lymphoma is characterized by diffuse lymphadenopathy, bone marrow involvement, and splenomegaly. Extranodal involvement is less common. Cytopenias are relatively common but constitutional symptoms of fever, night sweats, and weight loss are uncommon in the absence of transformation to diffuse large B cell lymphoma.
Diagnosis: The diagnosis is based on histology from a biopsy of a lymph node or other affected tissue. Incisional biopsy is preferred over needle biopsies in order to give adequate tissue to assign grade and assess for transformation. Immunohistochemical staining is positive in virtually all cases for cell surface CD19, CD20, CD10 and monoclonal immunoglobulin, as well as cytoplasmic expression of bcl-2 protein. The overwhelming majority of cases have the characteristic t(14;18) translocation involving the IgH/bcl-2 genes.
Risk stratification: The Follicular Lymphoma International Prognostic Index (FLIPI) uses five independent predictors of inferior survival: age > 60 years, hemoglobin <12 g/dL, serum LDH > normal, Ann Arbor stage III/IV, number of involved nodal areas >4. The presence of 0-1, 2, and ≥ 3 adverse factors defines low, intermediate, and high-risk disease. There are other clinical prognostic models but the FLIPI remains the most common. Other factors such as time to relapse of less than 2 years from chemoimmunotherapy and specific gene mutations may also be useful for prognosis. Regardless of the prognostic model used, modern therapies have demonstrably improved prognosis.
Risk-adapted therapy: Observation continues to be appropriate for asymptomatic patients with low bulk disease and no cytopenias. There is no overall survival advantage for early treatment with either chemotherapy or single agent rituximab. For patients needing therapy, most patients are treated with chemoimmunotherapy, which has improved response rates, duration of response and overall survival (OS). Randomized studies have shown additional benefit for maintenance rituximab. Lenalidomide was non-inferior to chemoimmunotherapy in a randomized front-line study and, when combined with rituximab, was superior to rituximab alone in relapsed FL. Kinase inhibitors, other immunotherapies, and stem cell transplantation (SCT) are also considered for recurrent disease.