Clonal Evolution in Follicular Lymphoma

Background: * Follicular lymphoma (FL) is the second most common form of non-Hodgkin lymphoma and is incurable with standard first-line systemic therapy * The clinical course of FL varies from slowly progressive over many years to a more rapid disease course that requires therapy shortly after diagnosis * Early initiation of therapy does not improve survival, and asymptomatic patients are often managed with an initial period of watchful waiting * Clinical prognostic indices predict survival, but cannot predict outcome for individual patients; biologic-based classifiers (gene-expression profiling and somatic mutational analyses) are more robust than clinical indices, but require prospective clinical validation from the time of diagnosis in the modern treatment era * Paired samples linked to clinical information can lead to the discovery and/or validation of therapeutic targets for FL patients at the highest risk of early disease progression Objective: Characterize the molecular biology and clinical course of FL patients, and evaluate the time to treatment initiation for those patients who require first-line systemic therapy. Eligibility: * Follicular lymphoma (grade 1-2, 3a) with no evidence of histological transformation * No previous cytotoxic, biologic or monoclonal antibody therapy for FL (previous radiation therapy permitted) * Age greater than or equal to 18 years * ECOG performance status of 0-2 Design: * Patients with FL who meet all eligibility criteria will enroll on the study for expert monitoring of their disease, improved risk-stratification, and donation of tissue and cellular products for research. Patients will be monitored prospectively until they require second-line systemic treatment or the patient decides to withdraw from the study; untreated patients will be followed with clinic visits every 4 months for the first 2 years. After 2 years, protocol-specified visits will be increased to every 6 months until 5 years. After 5 years, protocol-specified visits will be annually until disease progression requiring first-line therapy. * Patients without an indication for first-line systemic therapy at 2 years from initial study enrollment will be offered an optional biopsy of their lymph node and bone marrow. * During first-line systemic therapy, patients can continue being monitored on this study for post-therapy clonal evolution. Protocol-specified visits after therapy will be every 6 months until 3 years. After 3 years, protocol-specified visits will be annually until disease progression requiring second-line therapy. * Upon initiation of second-line therapy, if applicable, patients will move to survival follow-up only.