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Follicular Lymphoma (FL) is an indolent, neoplastic disorder of germinal center-derived B lymphocytes that afflicts approximately 14,000 people in the United States each year. It typically presents as a disseminated disorder with painless, diffuse lymphadenopathy and marrow infiltration, and may be associated with hepatosplenomegaly and circulating lymphoma cells in the blood. A characteristic translocation, t(14;18), is found in the cells of 85 percent of patients, which deregulates BCL2 protein expression and inhibits apoptosis of affected B cells. The cells typically express monoclonal surface immunoglobulin, CD10, CD19, CD20, CD22, CD45, and CD79a on their cell surface, but not CD5 or CD23. Patients are often asymptomatic at the time of presentation, and may live for many years in good health without therapy. On the other hand, most patients eventually develop progressive lymphadenopathy, causing symptoms mandating intervention. Many treatment regimens are effective at inducing remissions, including single-agent rituximab or chlorambucil; or several multidrug programs, including bendamustine plus rituximab (BR), rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). None of these therapies, however, is considered curative and most patients eventually relapse with recurrent disease. Autologous and allogeneic hematopoietic cell transplantation (HCT) can induce prolonged remissions in many patients with relapsed FL, but the role of HCT in this disease is controversial. Histologic transformation to aggressive lymphoma occurs in 30 to 40 percent of patients, usually leading to death within a few years of transformation.

Acronyms and Abbreviations

ADCC, antibody-dependent cellular cytotoxicity; BR, bendamustine and rituximab; CDC, complement-dependent cytotoxicity; CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; CR, complete response; CVP, cyclophosphamide, vincristine, prednisone; FCM, fludarabine, cyclophosphamide, mitoxantrone; FDG, fluoro-2-deoxyglucose; FL, follicular lymphoma; FND, fludarabine, mitoxantrone (Novantrone), dexamethasone; GELF, Groupe d’Etudes des Lymphomes Folliculaires; Gy, gray; HLA, histocompatibility locus antigen; IFN, interferon; IPI, international prognostic index; KLH, keyhole limpet hemocyanin; LDH, lactate dehydrogenase; NHL, non-Hodgkin lymphoma; ORR, overall response rate; OS, overall survival; PCR, polymerase chain reaction; PET, positron emission tomography; PFS, progression-free survival; PR, partial remission; ProMACE/MOPP, prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, procarbazine, prednisone; R-CHOP, rituximab plus CHOP; R-CVP, rituximab plus CVP; RIT, radioimmunotherapy; WHO, World Health Organization.


Follicular lymphoma (FL) is an indolent lymphoid neoplasm that is derived from mutated germinal center B cells and exhibits a nodular or follicular histologic pattern. It is typically composed of a mixture of small, cleaved follicle center cells (centrocytes) and large noncleaved follicle center cells (centroblasts). The disease has masqueraded under multiple monikers, including “nodular lymphoma” in the Rappaport classification, and “follicle center cell lymphoma” in the Working Formulation.1 The current World Health Organization (WHO) classification proposes the terms follicular lymphoma, grades 1, 2, and 3, to differentiate cases based on the numbers of centroblasts per high-power microscopic field (see “Lymph Node Morphology and Lymphocyte Immunophenotype” below).2


FL accounts for approximately 20 to 25 ...

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