What is the chemotherapy approach for patients with lymphoma?

Chemotherapy Approach for Lymphoma

The chemotherapy approach for lymphoma is determined by histologic subtype, stage, and patient fitness, with rituximab-based immunochemotherapy (R-CHOP) being the standard for CD20-positive aggressive B-cell lymphomas, while follicular lymphoma often requires a watch-and-wait approach until symptomatic, followed by rituximab-containing regimens. 1

Diagnostic Requirements Before Treatment

Proper diagnosis requires excisional lymph node biopsy with WHO classification and CD20 immunohistochemistry—fine needle aspiration is inadequate. 1, 2 Core biopsies should only be performed when lymph nodes are not easily accessible 2. Fresh frozen tissue should be stored for molecular analyses when possible 2.

Treatment by Lymphoma Subtype

Aggressive B-Cell Lymphomas (Diffuse Large B-Cell)

For CD20-positive large cell non-Hodgkin's lymphoma, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) given every 21 days for 8 cycles is the standard treatment for all stages. 1, 3

• CHOP remains the gold standard based on comparative trials showing no survival advantage with more intensive third-generation regimens, but with significantly less toxicity 4
• Rituximab should be added to CHOP for all CD20-positive B-cell lymphomas 2
• For limited stage disease (I-II), 4-6 cycles of R-CHOP followed by involved field radiotherapy is appropriate 5

Follicular Lymphoma (Indolent)

For early stage (I-II) follicular lymphoma, involved field radiotherapy (30-40 Gy) is the treatment of choice with curative potential. 2, 1

For advanced stage (III-IV) follicular lymphoma, treatment should only be initiated when symptoms develop—watch-and-wait is standard for asymptomatic patients. 2, 6

Treatment indications include 2, 6:

• B symptoms (fever >38°C, night sweats, >10% weight loss)
• Hematopoietic impairment
• Bulky disease or rapid progression
• Vital organ compression

When treatment is indicated 2, 1:

• Rituximab combined with chemotherapy (R-CHOP, R-CVP, or R-FCM) should be administered 2
• Rituximab maintenance substantially prolongs progression-free survival in relapsed disease with favorable side effects 2
• Single-agent alkylators (bendamustine, chlorambucil) or rituximab monotherapy remain alternatives for low-risk patients 2

Hodgkin Lymphoma

For early unfavorable Hodgkin lymphoma, 4 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by involved field radiotherapy is standard. 2, 7

• Six cycles of ABVD does not improve outcomes even for bulky disease, but increases bleomycin pulmonary toxicity 7
• For stage IA nodular lymphocyte-predominant Hodgkin lymphoma without risk factors, 30 Gy involved field radiotherapy alone is sufficient 2
• BEACOPP-escalated is an alternative for advanced stages 2

Relapsed/Refractory Disease

For relapsed large cell lymphoma in suitable patients (age <65, no major organ dysfunction), conventionally-dosed salvage chemotherapy followed by high-dose therapy with autologous stem cell transplantation is recommended. 2

Salvage regimens include 2:

• R-DHAP (rituximab, dexamethasone, high-dose cytarabine, cisplatin)
• R-ESHAP (rituximab, etoposide, methylprednisolone, high-dose cytarabine, cisplatin)
• R-ICE (rituximab, ifosfamide, carboplatin, etoposide)
• R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin)

Repeat biopsy is mandatory before salvage therapy to exclude transformation to aggressive lymphoma, particularly in follicular lymphoma. 2, 6

For patients unsuitable for high-dose therapy, the same salvage regimens may be combined with involved field radiotherapy, with individualized palliative care for elderly or comorbid patients 2.

Critical Staging and Monitoring

Before initiating chemotherapy 2, 1:

• CT scan of chest, abdomen, pelvis
• Bone marrow aspirate and biopsy
• Complete blood count, LDH, uric acid
• HIV and hepatitis B/C screening
• International Prognostic Index (IPI) calculation
• Echocardiography or MUGA scan if cumulative anthracycline dose requires monitoring 2
• Diagnostic spinal tap with prophylactic intrathecal chemotherapy for high-risk patients (IPI >2, bone marrow/testis/spine/skull base involvement) 2

Response Evaluation

Radiological assessment should be performed after 2-4 cycles of therapy, before stem cell collection, and after completion of all treatment. 2, 1

Patients with insufficient response should be evaluated for early salvage regimens 2, 1.

Common Pitfalls

• Never rely on fine needle aspiration for lymphoma diagnosis—it lacks sufficient tissue for proper subtyping 1
• Do not treat asymptomatic advanced follicular lymphoma—spontaneous regression occurs in 15-20% of cases 2
• Always obtain repeat biopsy at relapse to exclude transformation, especially in follicular lymphoma 2, 6
• Monitor cumulative anthracycline doses and cardiac function—specify prior anthracycline exposure in mg/m² 2
• Consider CNS prophylaxis in high-risk patients to prevent devastating CNS relapse 2