These entities have a natural history measured in years. Median survival is about 14 years. Follicular lymphoma is the most common indolent lymphoma, accounting for about one-third of all lymphoid malignancies.
Usually presents with painless peripheral lymphadenopathy, often involving several nodal regions. “B symptoms” (fever, sweats, weight loss) occur in 10%, less common than with Hodgkin's lymphoma. In about 25%, nodes wax and wane before the pt seeks medical attention. Median age is 55 years. Disease is widespread at diagnosis in 85%. Liver and bone marrow are commonly involved extranodal sites.
The tumor has a follicular or nodular growth pattern reflecting the follicular center origin of the malignant cell. The t(14;18) is present in 85% of cases, resulting in the overexpression of bcl-2, a protein involved in prevention of programmed cell death. The normal follicular center B cell is undergoing active mutation of the immunoglobulin variable regions in an effort to generate antibody of higher affinity for the selecting antigen. Follicular lymphoma cells also have a high rate of mutation that leads to the accumulation of genetic damage. Over time, follicular lymphomas acquire sufficient genetic damage (e.g., mutated p53) to accelerate their growth and evolve into diffuse large B-cell lymphomas that are often refractory to treatment. The majority of pts dying from follicular lymphoma have undergone histologic transformation. This transformation occurs at a rate of about 3% per year and is an attribute of the disease, not the treatment. The rate of histologic progression has decreased as treatment has improved. The international prognostic index for follicular lymphoma is shown in Table 67-3 Follicular Lymphoma International Prognostic Index-2 (FLIPI-2).
| TREATMENT | ||
Follicular LymphomaOnly 15% of pts have localized disease, but the majority of these pts are curable with radiation therapy. Although many forms of treatment induce tumor regression in advanced-stage pts, disease cure has been elusive. No therapy, single-agent alkylators, nucleoside analogues (fludarabine, cladribine), combination chemotherapy, radiation therapy, and biologic agents (interferon [IFN] α, monoclonal antibodies such as rituximab [anti-CD20]) are all considered appropriate. More than 90% of pts are responsive to treatment; complete responses are seen in about 50-75% of pts treated aggressively. The median duration of remission of pts treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) + rituximab exceeds 6 years. Bendamustine + rituximab is an active combination. Younger pts are being treated experimentally with high-dose therapy and autologous hematopoietic stem cells or minitransplant. It is not yet clear whether this is curative. Radioimmunotherapy with isotopes guided by anti-CD20 antibody (ibritumomab tiuxetan, In-111; tositumomab, I-131) may produce durable responses. Combination chemotherapy with or without monoclonal antibody maintenance may prolong survival and delay or prevent histologic progression, especially in pts with poor prognostic features. Remissions appear to last longer with chemotherapy plus rituximab or obinutuzumab; some data suggest that the longer remissions are leading to improved survival. |