No single genomic alteration seems responsible for the development of each of the spectrum of FL disorders. Rather, interactions between multiple genomic alterations appear to underlie this serial progression. In situ follicular lymphoma
In situ follicular lymphoma is an accumulation of monoclonal B cells (i.e. cells descendent from a single ancestral cell) in the germinal centers of lymphoid tissue. These cells commonly bear a pathological genomic abnormality, i.e. a translocation between position 32 on the long (i.e. "q") arm of chromosome 14 and position 21 on chromosome 18s q arm. This translocation juxtaposes the B-cell lymphoma 2 (BCL2) gene on chromosome 18 at position q21.33 near to the immunoglobulin heavy chain locus (IGH@) on chromosome 14 at position q21. In consequence, BCL2 overexpresses its product, BCL2 apoptosis regulator (i.e. Bcl2). Bcl2 functions to inhibit programmed cell death thereby prolonging cell survival. The overexpression of Bcl2 in the B-cells of ISFL is thought to be a critical factor in their pathological accumulation and subsequent malignant progression. Small numbers (e.g. 1 in 100,000) of circulating nucleated blood cells bearing this t(14:18)q32:q21) translocation are found in 50-67% of otherwise healthy individuals. The prevalence of this finding increases with age and years of tobacco smoking. Since most individuals with this translocation in their blood cells do not develop ISFL, the t(14:18)(q32:q21) translocation, while prolonging cell survival, must be just one step in the development of ISFN. This translocation is proposed to occur during the early development of immature bone marrow B-cells (i.e.
Other recently examined regimens include 1) the use of obinutuzumab instead of rituximab in the R-CHOP and R-CVP regiments to attain progression-free survival rates at 3 years of 80% for the obinutuzumab-chemotherapy regimen versus 73% for the rituximab-chemotherapy regimen and 2) the combination of rituximab with lenalidomide (no chemotherapy agent) versus various chemotherapy plus immunotherapy (principally rituximab) to achieve similar complete remission and 3 year progression-free survival rates but with rituximab plus lenalidomide causing less toxicity (i.e. severe neutropenia). Many of these studies did use rituximab maintenance therapy after induction therapy. Prevention
Several studies, while not conclusive, suggest that the early treatment of low risk FL reduces the incidence of the disease progressing to t-FL. The treatments used in these studies include chemotherapy, radiation therapy, and immunotherapy combinations plus rituximab maintenance therapy. Relapsed follicular lymphoma
Patients who relapse after initial therapy for FL may be followed closely without therapy if asymptomatic. When treatment is required, patients may be treated with the initial treatment regimen when such treatment led to a remission that lasted for at least one year; otherwise an alternative regimen is used. The regimens commonly used in relapsed lymphoma include R-CHOP, R-CVP, RFM (i.e. rituximab, fludarabine, and mitoxantrone), and  RB (Bendamustine plus rituximab). Patients who have early treatment failure (e.g. within 1–2 years of initial treatment) or multiple relapses have also been treated with either autologous (i.e. stem cells taken from patient) or allogeneic (i.e. stem cells taken from a donor) stem cell bone marrow transplantation.