What is the initial treatment approach for non-Hodgkin lymphoma (NHL)?

Initial Treatment Approach for Non-Hodgkin Lymphoma (NHL)

The initial treatment approach for non-Hodgkin lymphoma should be based on disease stage, with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) given every 21 days for 8 cycles being the current standard for CD20-positive large-cell NHL of all stages. 1

Diagnostic Workup

• An excisional lymph node biopsy is essential for proper diagnosis, providing adequate tissue for histopathological examination and immunohistochemistry studies with CD20 for proper subtyping according to the WHO classification 2
• Fine needle aspirations or core biopsies are inadequate for proper diagnosis and should only be used in rare emergency situations 2
• Complete staging requires:
  • CT scan of thorax, abdomen, and pelvis 1
  • Bone marrow aspirate and biopsy 1
  • Complete blood count, LDH, uric acid, and screening for HIV and hepatitis B/C 1
  • PET-CT for FDG-avid lymphomas 1

Staging and Risk Assessment

• The Ann Arbor staging system is used with mention of bulky disease 1
• For prognostic purposes, the International Prognostic Index (IPI) should be established 1
• General practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and prognostic factors 1

Treatment Approach Based on Disease Type

CD20-Positive Large Cell NHL (DLBCL)

• R-CHOP given every 21 days for 8 cycles is the current standard for CD20-positive large-cell NHL of all stages 1
• Rituximab is FDA-approved for previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens 3
• Shortening the interval between CHOP cycles to two weeks with growth factor support may be considered 1
• Dose reductions due to hematological toxicity should be avoided and febrile neutropenia justifies prophylactic use of hematopoietic growth factors in patients treated with curative intent 1

T-Cell Lymphoma

• CHOP remains the standard treatment for T-cell lymphomas 1
• For NK/T-cell lymphomas, asparaginase-based combination chemotherapy regimens are recommended for advanced disease 4

Limited Stage Disease (Stages I and II, nonbulky)

• For limited stage follicular lymphoma, radiotherapy is the treatment of choice with curative potential 2
• For limited stage DLBCL, R-CHOP with consideration of consolidation radiotherapy to sites of bulky disease, though benefit has not been proven 1

Advanced Stage Disease (Stage III or IV, or bulky Stage II)

• For advanced stage follicular lymphoma, treatment should be initiated upon symptoms, with primary chemotherapy options including combination regimens such as COP or CHOP 2
• For advanced DLBCL, R-CHOP for 8 cycles is standard 1

Special Considerations

• High-dose chemotherapy with stem cell transplantation in poor risk patients remains experimental 1
• Elderly patients (>65 years) may experience higher rates of adverse events, particularly cardiac and pulmonary complications 3
• Rituximab-related infusion reactions can be fatal; patients must be monitored closely during infusion 3
• Hepatitis B virus screening is essential as reactivation can occur with rituximab therapy 3

Response Evaluation

• Adequate radiological tests should be performed after 2-4 cycles and after the last cycle of treatment 1
• PET-CT should be used to assess response in FDG-avid histologies using the 5-point scale 1
• An initially pathologic bone marrow aspirate/biopsy should be repeated at the end of treatment 1
• Patients with incomplete or lacking response should be evaluated for early salvage regimens 1

Follow-up

• History and physical examination every 3 months for 2 years, every 6 months for 3 more years, and then once a year with attention to development of secondary tumors 1
• Blood count and LDH at 3,6,12, and 24 months, then only as needed for evaluation of suspicious symptoms 1
• Minimal adequate radiological examinations at 6,12, and 24 months after end of treatment 1
• Routine surveillance scans beyond this schedule are discouraged 1
• Evaluation of thyroid function in patients with irradiation to the neck at 1,2, and at least at 5 years 1

Treatment Outcomes

• Five-year disease-specific survival varies by histologic subtype: DLBCL (82%), follicular lymphoma (92%), marginal zone lymphoma (95%), small lymphocytic lymphoma (89%), Burkitt lymphoma (78%), mantle cell lymphoma (77%), and peripheral T cell lymphoma (77%) 5
• Despite favorable disease-specific survival, there does not appear to be a plateau in survival curves, suggesting that patients need continued follow-up even after 5 years of remission 5