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 receiving 2 cycles of ABVD followed by involved-site radiotherapy (30 Gy), intermediate-stage disease receiving 4 cycles of ABVD plus radiotherapy, and advanced-stage disease receiving 6 cycles of ABVD or escalated BEACOPP chemotherapy alone. 1

Initial Staging and Risk Assessment

Before initiating treatment, comprehensive staging is mandatory to guide therapy selection:

• Imaging requirements: Contrast-enhanced CT scan of neck, chest, and abdomen is mandatory, with baseline PET-CT strongly recommended if available 1
• Bone marrow biopsy: Not indicated if PET-CT is performed, but mandatory if PET-CT unavailable 1
• Laboratory evaluation: Complete blood count, ESR, and blood chemistry including C-reactive protein, alkaline phosphatase, albumin, and LDH are required 1
• Infectious disease screening: Hepatitis B, hepatitis C, and HIV testing is compulsory before treatment 1
• Cardiac and pulmonary assessment: Function tests must be completed before anthracycline-based therapy 1

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

• Limited stage: Clinical stage I-II without risk factors
• Intermediate stage: Clinical stage I-II with ≥1 risk factor (large mediastinal mass >1/3 thoracic width or >7.5 cm, extranodal involvement, massive splenic involvement, elevated ESR >30 mm/h for B-stages or >50 mm/h for A-stages, ≥3 lymph node areas, age >60 years)
• Advanced stage: Clinical stage III-IV

Treatment by Stage

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

Two cycles of ABVD followed by involved-site radiotherapy (ISRT) at 30-36 Gy is the standard of care. 1

• ABVD consists of doxorubicin, bleomycin, vinblastine, and dacarbazine 1
• ISRT is preferred over involved-field radiotherapy (IFRT) to minimize radiation exposure 1
• Chemotherapy alone may be considered when late radiation toxicity risks outweigh short-term disease control benefits 1

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

Four 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 escalated BEACOPP followed by 2 cycles of ABVD plus 30 Gy ISRT can be offered 1
• Interim PET-CT after 2 cycles is critical: PET-positive patients should switch to 2 cycles of escalated BEACOPP before ISRT 1
• Bleomycin should not exceed 2 cycles in patients >60 years due to pulmonary toxicity risk 1

Advanced-Stage Disease (Stage III-IV)

For patients ≤60 years, either 6 cycles of ABVD or 4-6 cycles of escalated BEACOPP is recommended, with chemotherapy alone as the primary modality. 1

The most recent high-quality evidence shows escalated BEACOPP provides superior overall survival:

• Six cycles of escalated BEACOPP achieves 95% 5-year survival compared to 88% with ABVD—a 7% absolute survival benefit 2
• However, ABVD remains widely used due to better tolerability and lower toxicity profile 1

PET-adapted treatment strategies 1:

• After 2 cycles of ABVD: If interim PET is negative, omit bleomycin in cycles 3-6, especially in elderly patients or those at increased lung toxicity risk 1
• After 2 cycles of ABVD: If interim PET is positive, switch to escalated BEACOPP 1
• After 2 cycles of escalated BEACOPP: PET-negative patients receive only 2 more cycles; PET-positive patients need 4 more cycles 1

Radiotherapy in advanced disease is restricted to patients with PET-positive residual lymphoma ≥2.5 cm after completing chemotherapy 1

Critical contraindication: BEACOPP regimen should NOT be given to patients >60 years due to excessive toxicity 1

Elderly Patients (>60 Years)

ABVD-based chemotherapy is the standard of care for fit elderly patients, with bleomycin discontinued after the second cycle. 1

Special Histologic Subtype: Nodular Lymphocyte-Predominant HL

• Stage IA without risk factors: 30 Gy ISRT alone is standard treatment 1
• All other stages: Treat identically to classical HL 1
• Recurrent disease: Rituximab or ofatumumab as single agent is effective for localized relapses 1

Relapsed/Refractory Disease

For most patients with relapsed or refractory HL, high-dose chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT) is the treatment of choice. 1

Salvage chemotherapy regimens before ASCT include DHAP, IGEV, or ICE 1:

• Single-agent brentuximab vedotin may be sufficient as salvage therapy in select patients 1
• Achieving PET-negative status should be the goal of salvage therapy regardless of protocol 1
• Consolidation with brentuximab vedotin following HDCT and ASCT is recommended for patients with poor-risk factors 1

For patients failing ASCT 1, 3:

• Single-agent brentuximab vedotin is an option 1
• Nivolumab and pembrolizumab are FDA-approved for patients with disease recurrence after HDCT/ASCT and brentuximab vedotin 1, 3
• Allogeneic stem cell transplant should be considered in young, chemosensitive patients in good condition after careful risk-benefit evaluation 1
• Gemcitabine-based palliative chemotherapy and/or regional radiotherapy for patients with multiple relapses and no other options 1

Response Evaluation and Monitoring

Interim staging after 2 cycles and final staging after treatment completion 1:

• Physical examination, laboratory analysis, and repeat of initially abnormal radiographic tests 1
• PET-CT after 2 cycles identifies patients at risk for incomplete response 1
• Positive end-of-treatment PET scans indicate partial remission with high early relapse risk 1

Follow-up schedule 1:

• History and physical exam every 3 months for 6 months, then every 6 months until year 4, then annually 1
• Laboratory analysis and chest X-ray at 6,12, and 24 months 1
• CT scan once to confirm remission; surveillance scans not indicated unless clinical symptoms occur 1
• Thyroid function (TSH) annually if neck irradiation performed 1
• Breast cancer screening for women receiving chest irradiation at premenopausal age, especially <25 years: clinical examination and mammography after age 40-50 1

Critical Pitfalls to Avoid

• Never use staging laparotomy—it is not recommended 1
• Do not give bleomycin beyond 2 cycles in patients >60 years due to pulmonary toxicity 1
• Do not use BEACOPP in patients >60 years—excessive toxicity without proven benefit 1
• Do not perform routine surveillance CT scans after confirming remission—follow clinically 1
• Do not ignore interim PET results—they guide treatment intensification or de-escalation 1