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Non-Hodgkin's Lymphoma

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Indolent NHL

Indolent non-Hodgkin lymphoma (NHL) includes the following subtypes:

  • Follicular lymphoma.
  • Lymphoplasmacytic lymphoma (Waldenström macroglobulinemia).
  • Marginal zone lymphoma.
  • Splenic marginal zone lymphoma.
  • Primary cutaneous anaplastic large cell lymphoma.

Follicular Lymphoma

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Understanding Non-Hodgkin Lymphoma -- Symptoms

Symptoms of non-Hodgkin lymphoma may include: Painless swelling of one or more lymph nodes, with no recent infection. Swelling may be intermittent. Swelling, fluid accumulation, or pain in the abdomen. Shortness of breath, wheezing, or coughing. Bloody stool or vomit. Swelling of the face, neck, and arms. Blockage of urine flow. Bone pain. Unexplained weight loss amounting to 10% of body weight over six months. Fever lasting for at least 14 consecutive days, usually in...

Read the Understanding Non-Hodgkin Lymphoma -- Symptoms article > >

Follicular lymphoma comprises 20% of all NHLs and as many as 70% of the indolent lymphomas reported in American and European clinical trials.[1,2,3] Most patients with follicular lymphoma are age 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.[4]

Prognosis

Despite the advanced stage, the median survival ranges from 8 to 15 years, leading to the designation of being indolent.[5,6,7] Patients with advanced-stage follicular lymphoma are not cured with current therapeutic options.[8] The rate of relapse is fairly consistent over time, even in patients who have achieved complete responses to treatment.[9] Watchful waiting, i.e., the deferring of treatment until the patient becomes symptomatic, is an option for patients with advanced-stage follicular lymphoma.[10] An international index for follicular lymphoma (i.e., the Follicular Lymphoma International Prognostic Index [FLIPI]) [11,12,13] identified five significant risk factors prognostic of overall survival (OS):

  1. Age (≤60 years vs. >60 years).
  2. Serum lactate dehydrogenase (LDH) (normal vs. elevated).
  3. Stage (stage I or stage II vs. stage III or stage IV).
  4. Hemoglobin level (≥120 g/L vs. <120 g/L).
  5. Number of nodal areas (≤4 vs. >4).

Patients with none or one risk factor have an 85% 10-year survival rate, while three or more risk factors confer a 40% 10-year survival rate.[11] As a revised FLIPI, an elevated beta-2-microglobulin and lymph node size of more than 6 cm are proposed prognostic factors instead of serum LDH and the number of nodal areas.[14] 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).[15]

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 approaches

Therapeutic options include watchful waiting; rituximab, an anti-CD20 monoclonal antibody, alone or with purine nucleoside analogs; oral alkylating agents; and combination chemotherapy.[16] Radiolabeled monoclonal antibodies, vaccines, and autologous or allogeneic bone marrow or peripheral stem cell transplantation are also under clinical evaluation.[16] 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. Follicular lymphoma in situ and primary follicular lymphoma of the duodenum are particularly indolent variants that rarely progress and rarely require therapy.[17,18]

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