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Leukemia & Lymphoma

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Adult Non-Hodgkin Lymphoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - 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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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]


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]

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