What is the recommended treatment plan for a patient with Hodgkin's lymphoma?

Treatment of Hodgkin's Lymphoma

Treatment for Hodgkin's lymphoma is determined by disease stage and risk stratification, with limited-stage disease treated with 2 cycles of ABVD followed by involved-site radiotherapy (30 Gy), intermediate-stage disease with 4 cycles of ABVD plus radiotherapy, and advanced-stage disease with 6 cycles of ABVD or 4-6 cycles of BEACOPPescalated chemotherapy alone. 1

Initial Staging and Risk Assessment

Before initiating treatment, complete staging is mandatory:

• Contrast-enhanced CT scan of neck, chest, and abdomen is required, with baseline PET-CT strongly recommended if available 1, 2
• Bone marrow biopsy is not indicated if PET-CT is performed, but must be done if PET-CT is unavailable 1
• Laboratory evaluation including complete blood count, ESR, and blood chemistry (C-reactive protein, alkaline phosphatase, albumin, LDH) 1
• Screening for hepatitis B, hepatitis C, and HIV is mandatory before treatment 1, 2
• Cardiac and pulmonary function testing must be completed prior to anthracycline-based therapy 1, 3

Risk stratification follows the Ann Arbor staging system with three categories 1:

Limited stage: Clinical stage I-II without risk factors 1

Intermediate stage: Clinical stage I-II with ≥1 risk factor:

• Large mediastinal mass (>1/3 thoracic width on chest X-ray or >7.5 cm on CT) 1
• Extranodal involvement 1
• Massive splenic involvement (>5 nodules or diffuse enlargement) 1
• Elevated ESR (>30 mm/h for B-stages or >50 mm/h for A-stages) 1
• Extensive lymph node involvement (≥3 lymph node areas) 1
• Age >60 years 1

Advanced stage: Clinical stage III-IV 1

Treatment by Stage

Limited-Stage Disease (Stage I-II Without Risk Factors)

• 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by involved-site radiotherapy (ISRT) at 30 Gy is the standard of care 1
• ISRT is preferred over involved-field radiotherapy (IFRT) to minimize long-term toxicity 1
• Chemotherapy alone may be offered when the late risks of radiotherapy outweigh the short-term benefit of improved disease control 1

Intermediate-Stage Disease (Stage I-II With Risk Factors)

• 4 cycles of ABVD followed by ISRT at 30 Gy is the standard approach 1
• For patients ≤60 years eligible for intensive treatment, 2 cycles of BEACOPPescalated followed by 2 cycles of ABVD and 30 Gy ISRT can be considered 1
• If interim PET after 2 cycles of ABVD is positive, switch to 2 cycles of BEACOPPescalated before ISRT 1

Advanced-Stage Disease (Stage III-IV)

For patients ≤60 years:

• 6 cycles of ABVD or 4-6 cycles of BEACOPPescalated are both acceptable options 1
• BEACOPPescalated provides superior overall survival (95% at 5 years vs 88% with ABVD), representing a 7% absolute survival benefit 4
• After 2 cycles of ABVD, omit bleomycin in cycles 3-6 if interim PET is negative, particularly in elderly patients or those at increased risk for lung toxicity 1
• If interim PET after 2 cycles of ABVD is positive, switch to BEACOPPescalated 1
• After 2 cycles of BEACOPPescalated, PET-negative patients receive only 2 more cycles, while PET-positive patients need 4 more cycles 1
• Radiotherapy is restricted to patients with PET-positive residual lymphoma ≥2.5 cm after completing chemotherapy 1

For patients >60 years:

• ABVD-based chemotherapy is the standard of care 1
• BEACOPP regimen should NOT be given to patients >60 years due to excessive toxicity 1
• Bleomycin should be discontinued after the second cycle in this age group 1, 2

Special Considerations for Organ Dysfunction

For patients with chronic liver disease, acute kidney injury, or cardiomyopathy:

• Modified ABVD without bleomycin is recommended to avoid pulmonary toxicity 2
• BEACOPP is absolutely contraindicated in the setting of significant organ dysfunction 2
• Dose adjustment of renally cleared agents based on creatinine clearance is necessary 2
• Aggressive hydration protocols before and after chemotherapy are essential 2
• Single-agent brentuximab vedotin may be considered for patients unable to tolerate standard chemotherapy 2
• Frequent monitoring of liver, kidney, and cardiac function before each treatment cycle is mandatory 2

Response Evaluation

• Interim PET-CT after 2 cycles identifies patients at risk for incomplete response and guides treatment intensification 1
• End-of-treatment PET-CT should be performed after completing all therapy 1, 2
• Positive end-of-treatment PET scans indicate partial remission with high risk for early relapse 1

Relapsed/Refractory Disease

• High-dose chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT) is the standard of care for most patients with relapsed disease 1
• Salvage regimens include DHAP, IGEV, or ICE before HDCT and ASCT 1
• Achieving PET-negative status should be the goal of salvage therapy regardless of the protocol used 1
• Brentuximab vedotin consolidation following HDCT and ASCT is recommended for patients with poor-risk factors 1
• For patients failing ASCT, brentuximab vedotin, nivolumab, or pembrolizumab are approved options 1
• Allogeneic stem cell transplant should be considered in young, chemosensitive patients in good condition after ASCT failure 1

Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

• Stage IA NLPHL without risk factors is treated with 30 Gy ISRT alone 1
• All other NLPHL patients are treated identically to classical Hodgkin lymphoma 1
• Localized NLPHL relapses can be treated with rituximab or ofatumumab as single agents 1

Follow-Up and Surveillance

• History and physical examination every 3 months for 1 year, every 6 months for 3 years, then annually 1
• Laboratory analysis and chest X-ray at 6,12, and 24 months, then as clinically indicated 1
• CT scan once to confirm remission status; routine surveillance CT scans are not recommended 1
• Thyroid function testing annually if the neck was irradiated 1
• Breast cancer screening for women who received chest irradiation at premenopausal age, especially <25 years, with clinical examination and mammography after age 40-50 1

Critical Pitfalls to Avoid

• Never use BEACOPP in patients >60 years due to unacceptable toxicity 1
• Do not continue bleomycin beyond 2 cycles in elderly patients or those at risk for pulmonary toxicity 1, 2
• Avoid staging laparotomy, which is not recommended 1
• Do not perform routine surveillance CT scans after confirming remission, as they are not indicated unless clinical symptoms occur 1
• Ensure reproductive counseling and fertility preservation (sperm banking, oocyte collection, ovarian tissue cryopreservation) before treatment initiation 1