Follicular, small-cleaved cell lymphoma and follicular mixed small-cleaved and large cell lymphoma do not have reproducibly different disease-free survival or OS.
Therapeutic options include watchful waiting; rituximab, an anti-CD20 monoclonal antibody, alone or with purine nucleoside analogs; oral alkylating agents; and combination chemotherapy. Radiolabeled monoclonal antibodies, vaccines, and autologous or allogeneic bone marrow or peripheral stem cell transplantation are also under clinical evaluation.[16,17] Currently, no randomized trials have mature results to guide clinicians about the initial choice of rituximab, nucleoside analogs, alkylating agents, combination chemotherapy, radiolabeled monoclonal antibodies, or combinations of these options. On a comparative basis, it is difficult to prove benefit when relapsing disease is followed with watchful waiting, or when the median survival is more than 10 years. Follicular lymphoma in situ and primary follicular lymphoma of the duodenum are particularly indolent variants that rarely progress and rarely require therapy.[18,19] A so-called pediatric-type nodal follicular lymphoma has indolent behavior and rarely recurs; adult patients with this histologic variant are characterized by a lack of bcl-2 rearrangement in conjunction with a Ki-67 proliferation index greater than 30% and a localized stage I presentation.
Patients with indolent lymphoma may experience a relapse with a more aggressive histology. If the clinical pattern of relapse suggests that the disease is behaving in a more aggressive manner, a biopsy should be performed. Documentation of conversion to a more aggressive histology requires an appropriate change to a therapy applicable to that histologic type. Rapid growth or discordant growth between various disease sites may indicate a histologic conversion. The risk of histologic transformation was 30% by 10 years in a retrospective review of 325 patients from diagnosis between 1972 and 1999. In this series, high-risk factors for subsequent histologic transformation were advanced stage, high-risk FLIPI, and expectant management. The 5-year OS rate was more than 50% for 172 patients who had biopsy-proven, aggressive-histology transformation in a multicenter cohort study employing rituximab plus anthracycline or platinum-based chemotherapy, or similar therapy followed by autologous or allogeneic stem cell transplantation.[23,24]