Follicular lymphoma comprises 20% of all non-Hodgkin’s lymphomas and as many as 70%
of the indolent lymphomas reported in American and European clinical
trials.[7,8,11] Most patients with follicular lymphoma are 50 years and older and
present with widespread disease at diagnosis. Nodal involvement is most common and is
often accompanied by splenic and bone marrow disease. Rearrangement of the bcl-2 gene is present in more than 90% of patients with
follicular lymphoma; overexpression of the bcl-2 protein is associated with
the inability to eradicate the lymphoma by inhibiting apoptosis.
Despite the advanced
stage, the median survival ranges from 8 to 15 years, leading to the
designation of being indolent.[13,14,15] Patients
with advanced-stage follicular lymphoma are not cured with current therapeutic
options. The rate of relapse is fairly consistent over time, even in patients
who have achieved complete responses to treatment. Watchful waiting, i.e., the deferring
of treatment until the patient becomes symptomatic, is an option for patients
with advanced-stage follicular lymphoma. An international index for follicular lymphoma (i.e., the Follicular Lymphoma International Prognostic Index [FLIPI])[19,20,21] identified five significant risk factors prognostic of overall survival (OS):
- Age (=60 years vs. >60 years).
- Serum lactate dehydrogenase (normal vs. elevated).
- Stage (stage I or stage II vs. stage III or stage IV).
- Hemoglobin level (=120 g/L vs. <120 g/L).
- Number of nodal areas (=4 vs. >4).
Patients with 0 to 1 risk factors have an 85% 10-year survival rate, while 3 or more risk factors confer a 40% 10-year survival rate. Gene expression profiles of tumor biopsy specimens suggest that follicular lymphoma that is surrounded by infiltrating T-lymphocytes has a much longer median survival (13.6 years) than follicular lymphoma that is surrounded by dendritic and monocytic cells (3.9 years) (P < .001). These infiltrating nonmalignant cells may be valuable therapeutic targets.
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
monoclonal antibodies, vaccines, and autologous or allogeneic bone marrow or
peripheral stem cell transplantation are also under clinical evaluation. Currently, no randomized trials 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.
LYMPHOPLASMACYTIC LYMPHOMA (WALDENSTRöM’S MACROGLOBULINEMIA)
Lymphoplasmacytic lymphoma is usually associated with a monoclonal serum
paraprotein of immunoglobulin M (IgM) type (Waldenström’s macroglobulinemia).[25,26,27]
Most patients have bone marrow, lymph node, and splenic involvement, and some
patients may develop hyperviscosity syndrome. Other lymphomas may also be
associated with serum paraproteins.