The Ann Arbor technique designates stages I and II as one disease site and more than one lymph node site, respectively, on the same side of the diaphragm. Stage III involves multiple lymph node sites on both sides of the diaphragm. Stage IV disease includes extranodal involvement in the liver, the lungs, or most commonly, the bone marrow. Certain clinical and laboratory parameters combined with staging provide better prognostic information for patients with NHL compared with information from staging alone. The International Prognostic Index (IPI) score was initially developed for more aggressive lymphomas and was followed by the Follicular Lymphoma International Prognostic Index (FLIPI) score for the second most common form of lymphoma4-6 (Table 2).


The nearly universal expression of the CD20 receptor on B-cell lymphomas is a target of rituximab (Rituxan) therapy. Rituximab is a monoclonal antibody that binds to the CD20 receptor. Although the agent is effective as a single agent to treat various types of B-cell lymphomas, it is often used in conjunction with chemotherapy to increase its efficacy.

A variety of therapeutic options have been used to treat low-grade B-cell lymphomas. The generally accepted goal of treatment is to control the disease, not cure the patient because these patients are often elderly and have numerous comorbidities. The risks inherent with the only curative approach, allogeneic stem cell transplant, have a higher mortality rate than the disease. Rituximab combinations with chemotherapeutic agents are the mainstay of therapy. Until recently, the chemotherapy regimens used most often were R-CVP (rituximab plus cyclophosphamide [Cytoxin, Neosar, generics], vincristine [Oncovin, Vincasar, generics], prednisone) and R-CHOP (rituximab plus cyclophosphamide, doxorubicin [hydroxydoxorubicin, Andriamycin, Doxil, Rubex, generics], vincristine [Oncovin], and prednisone). However, bendamustine (Treanda), a recently marketed chemotherapy agent, plus rituximab has the same efficacy as R-CHOP with less toxicity.7-10 An equally debatable issue is when to treat low-grade B-cell lymphomas.

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No studies have demonstrated that treating the disease before the patient becomes symptomatic or excessive marrow involvement is apparent (such as development of anemia and thrombocytopenia) results in better patient outcomes. However, the opposite is true for diffuse large B-cell lymphoma. The gold standard for achieving a complete remission is treatment with R-CHOP as early as possible, as untreated disease has a definitive impact on patient survival. Approximately 30% of patients who experience a relapse will require extremely high doses of chemotherapy and radiation followed by a stem cell transplant. Using an autologous source of stem cells most often minimizes the complications following transplant.11

Mantle cell lymphoma has the worst characteristics of both low-grade lymphomas and large B-cell intermediate-grade lymphomas. Similar to low-grade lymphomas, mantle cell lymphoma cannot be cured; and the same as large B-cell intermediate-grade lymphomas, it has a fairly rapid and pernicious course. Treatment is quite controversial; R-CHOP alone is not found to be adequate. Use of higher-dosage chemotherapy regimens with or without autologous stem cell support has been met with resistance. An aggressive form of B-cell lymphoma therapy involves regimens of conventional chemotherapy administered with rituximab and higher doses of cyclophosphamide in conjunction with cytarabine (Cytosar-U, DepoCyt), referred to as R-hyper-CVAD (rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone [Decadron, Dexamethasone Intensol, Dexpak Taperpak, generics]).1

T-cell lymphomas have a much lower incidence; therefore, the pharmaceutical industry has much less focus on this form of lymphoma. Patients with low-grade forms of T-cell lymphomas have benefited from treatment interventions ranging from topical agents to systemic approaches with chemotherapy and biologic therapies.12

The intermediate forms of T-cell lymphoma are primarily treated with CHOP-like regimens without rituximab, as these lymphomas do not express the CD20 receptor.13,14 A new anti-CD30 monoclonal antibody, known as brentuximab vedotin, seems to be highly effective and may become the “rituximab” for this type of lymphoma.15 The peripheral T-cell lymphomas (PTCLs) are grouped together in therapeutic interventions, and treatment with CHOP-like regimens has limited success as these patients often relapse. The most effective treatment options are high doses of chemotherapy with or without radiation, followed by either autologous or allogeneic stem cell transplant. Recently a new chemotherapeutic agent, pralatrexate (Folotyn), has demonstrated effectiveness in treating patients with PTCL relapse.16

High-grade T-cell lymphomas are often managed in a similar manner as their aggressive B-cell counterparts. Unfortunately, not much success has been achieved in treating the virally associated HTLV lymphoma, which is highly refractory to various treatments.


Although disease staging is an important assessment in all malignancies, an accurate identification of subtype is paramount in management of the disease process of NHLs. Various classification systems are established based on the aggressiveness of the disease type, and maintaining clinical application of these systems is useful. Typically, more aggressive therapeutic interventions are matched to high-grade disease; therefore, the potential for over- or undertreatment of the disease is minimized. ONA

Donald Fleming is an oncologist at the Cancer Care Center, Davis Memorial Hospital, Elkins, West Virginia, and a member of the Oncology Nurse Advisor editorial board.

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2. Matasar MJ, Zelenetz AD. Overview of lymphoma diagnosis and management. Radiol Clin North Am. 2008;46(2):175-198.

3. Good DJ, Gascoyne RD. Classification of non-Hodgkin’s lymphoma. Hematol Oncol Clin North Am. 2008;22(5):781-805.

4. A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med. 1993;329(14):987-994.

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6. Suzumiya J, Ohshima K, Tamura K, et al; International Peripheral T-Cell Lymphoma Project. The International Prognostic Index predicts outcome in aggressive adult T-cell leukemia/lymphoma: analysis of 126 patients from the International Peripheral T-Cell Lymphoma Project. Ann Oncol. 2009;20(4):715-721.

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8. Salles G, Seymour JF, Offner F, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomized controlled trial. Lancet. 2011;377(9759):42-51.

9. Rummel MJ, Kaiser U, Balser C, et al. Bendamustine plus rituximab versus fludarabine plus rituximab in patients with relapsed follicular, indolent and mantle cell lymphomas—final results of the randomized phase III study NHL 2-2003 on behalf of the StiL (Study Group Indolent Lymphomas, Germany). Poster presented at: 52nd ASH Annual Meeting and Exposition, December 4-7, 2010; Orlando, FL. Abstract 856.

10. Hochster H, Weller E, Gascoyne RD, et al: Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 study. J Clin Oncol. 2009;27(10):1607-1614.

11. Pfreundschuh M, Trümper L, Osterborg A, et al; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomized controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7(5):379-391.

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13. Savage KJ, Harris NL, Vose JM, et al; International Peripheral T-Cell Lymphoma Project. ALK-anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood. 2008;111(12):5496-5504.

14. Corradini P, Tarella C, Zallio F, et al. Long term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation. Leukemia. 2006;20(9):1533-1538.

15. Younes A, Bartlett NL, Leonard JP, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363(19):1812-1821.

16. O’Connor OA, Horwitz S, Hamlin P, et al. Phase II-I-II study of two different doses and schedules of pralatrexate, a high-affinity substrate for the reduced folate carrier, in patients with relapsed or refractory lymphoma reveals marked activity in T-cell malignancies. J Clin Oncol. 2009;27(26):4357-4364.

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