(Refer to the PDQ summaries on Chronic Lymphocytic Leukemia Treatment; Mycosis Fungoides/Sézary Syndrome Treatment; Hairy Cell Leukemia Treatment; and Adult Hodgkin Lymphoma Treatment for more information.)
Diffuse large cell lymphoma
Diffuse large B-cell lymphoma is the most common of the NHLs and comprises 30% of newly diagnosed cases. Most patients present with rapidly enlarging masses, often with symptoms both locally and systemically (designated B symptoms with fever, recurrent night sweats, or weight loss). (Refer to the PDQ summary on Fever, Sweats, and Hot Flashes and for more information on weight loss, refer to the Nutrition in Cancer Care summary.) The vast majority of patients with localized disease are curable with combined modality therapy or combination chemotherapy alone. For patients with advanced-stage disease, 50% of presenting patients are cured with doxorubicin-based combination chemotherapy and rituximab.[100,101,102]
An International Prognostic Index (IPI) for aggressive NHL (diffuse large cell lymphoma) identifies five significant risk factors prognostic of OS:
- Age (≤60 years vs. >60 years).
- Serum LDH (normal vs. elevated).
- Performance status (0 or 1 vs. 2–4).
- Stage (stage I or stage II vs. stage III or stage IV).
- 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, CNS, liver, lung, and spleen. Age-adjusted and stage-adjusted modifications of this IPI are used for younger patients with localized disease. Patients at high risk of relapse may be considered for clinical trials. 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.[106,107,108,109,110]
CNS prophylaxis (usually with four to six injections of methotrexate intrathecally) is recommended for patients with paranasal sinus or testicular involvement. Some clinicians are employing high-dose intravenous methotrexate (usually four doses) as an alternative to intrathecal therapy because drug delivery is improved, and patient morbidity is decreased. CNS prophylaxis for bone marrow involvement is controversial; some investigators recommend it, others do not.[112,113] A retrospective analysis of 605 patients with diffuse large cell lymphoma who did not receive prophylactic intrathecal therapy identified an elevated serum LDH and more than one extranodal site as independent risk factors for CNS recurrence. Patients with both risk factors have a 17% probability of CNS recurrence at 1 year after diagnosis (95% confidence interval [CI], 7%–28%) versus 2.8% (95% CI, 2.7%–2.9%) for the remaining patients.[Level of evidence: 3iiiDiii] Some cases of large B-cell lymphoma have a prominent background of reactive T-cells and often of histiocytes, so-called T-cell/histocyte-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 diffuse large B-cell lymphoma.[115,116,117] Some patients with diffuse large B-cell lymphoma at diagnosis have a concomitant indolent small B-cell component; while OS appears similar after multidrug chemotherapy, there is a higher risk of indolent relapses.