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

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

  • Diffuse large B-cell lymphoma.
  • Mediastinal large B-cell lymphoma (primary mediastinal large B-cell lymphoma).
  • Follicular large cell lymphoma.
  • Anaplastic large cell lymphoma.
  • Extranodal NK-/T-cell lymphoma.
  • Lymphomatoid granulomatosis.
  • Angioimmunoblastic T-cell lymphoma.
  • Peripheral T-cell lymphoma.
  • Enteropathy-type intestinal T-cell lymphoma.
  • Intravascular large B-cell lymphoma (intravascular lymphomatosis).
  • Burkitt lymphoma/diffuse small noncleaved-cell lymphoma.
  • Lymphoblastic lymphoma.
  • Adult T-cell leukemia/lymphoma.
  • Mantle cell lymphoma.
  • Polymorphic posttransplantation lymphoproliferative disorder.
  • True histiocytic lymphoma.
  • Primary effusion lymphoma.

Diffuse Large B-cell Lymphoma

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Diffuse large B-cell lymphoma (DLBCL) is the most common of the NHLs and comprises 30% of newly diagnosed cases.[1] Most patients present with rapidly enlarging masses, often with both local and systemic symptoms (designated B symptoms with fever, recurrent night sweats, or weight loss). (Refer to the PDQ summary on Hot Flashes and Night Sweats and the PDQ summary on Nutrition in Cancer Care for more information on weight loss.)

Some cases of large B-cell lymphoma have a prominent background of reactive T cells and often of histiocytes, so-called T-cell/histiocyte-rich large B-cell lymphoma. This subtype of large cell lymphoma has frequent liver, spleen, and bone marrow involvement; however, the outcome is equivalent to that of similarly staged patients with DLBCL.[2,3,4] Some patients with DLCBL at diagnosis have a concomitant indolent small B-cell component; while overall survival (OS) appears similar after multidrug chemotherapy, there is a higher risk of indolent relapse.[5]


The vast majority of patients with localized disease are curable with combined-modality therapy or combination chemotherapy alone.[6] For patients with advanced-stage disease, 50% of presenting patients are cured with doxorubicin-based combination chemotherapy and rituximab.[7,8,9]

An International Prognostic Index (IPI) for aggressive NHL (diffuse large cell lymphoma) identifies five significant risk factors prognostic of OS:[10]

  1. Age (≤60 years vs. >60 years).
  2. Serum lactate dehydrogenase (LDH) (normal vs. elevated).
  3. Performance status (0 or 1 vs. 2-4).
  4. Stage (stage I or stage II vs. stage III or stage IV).
  5. Extranodal site involvement (0 or 1 vs. 2-4).

Patients with two or more risk factors have a less than 50% chance of relapse-free survival and OS at 5 years. This study also identifies patients at high risk of relapse based on specific sites of involvement, including bone marrow, central nervous system (CNS), liver, lung, and spleen. Age-adjusted and stage-adjusted modifications of this IPI are used for younger patients with localized disease.[11] The bcl-2 gene and rearrangement of the myc gene or dual overexpression of the myc gene, or both, confer a particularly poor prognosis.[12,13,14,15] Patients at high risk of relapse may be considered for clinical trials.[16] Molecular profiles of gene expression using DNA microarrays may help to stratify patients in the future for therapies directed at specific targets and to better predict survival after standard chemotherapy.[17,18,19,20,21] Patients who have DLBCL with coexpression of CD20 and CD30 may define a subgroup with a unique molecular signature, a more favorable prognosis, and possible therapeutic implication for the use of anti-CD30-specific therapy, such as brentuximab vedotin.[22]

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