What are the current updated guidelines for managing classical Hodgkin lymphoma?

Current Updated Guidelines for Management of Classical Hodgkin Lymphoma

The current standard management of classical Hodgkin lymphoma involves risk-stratified combined modality therapy with ABVD chemotherapy followed by involved-field radiotherapy for early-stage disease, and full-term ABVD chemotherapy (6-8 cycles) for advanced-stage disease, with PET/CT-based response assessment using the Deauville 5-point scale to guide treatment decisions. 1

Initial Workup and Staging

Mandatory Laboratory Assessments

• Complete blood count with differential to assess for cytopenias 2
• Serum albumin and LDH as prognostic markers and indicators of tumor burden 2
• Erythrocyte sedimentation rate (ESR) for risk stratification 2
• HBV, HCV, and HIV serology, as these infections impact treatment decisions 2
• Pregnancy test in women of fertile age before therapy initiation 2

Imaging and Staging Studies

• CT scan of neck, chest, abdomen, and pelvis for volumetric assessment and identification of bulky disease (mediastinal mass >1/3 maximum horizontal thoracic diameter on chest X-ray) 1, 3
• FDG-PET or CT-PET scan is strongly recommended for accurate baseline staging and is necessary for PET-aided response assessment during treatment 1, 2
• Monolateral bone marrow biopsy should be performed in patients with B symptoms and/or stage III/IV disease and/or blood count abnormalities 1

Pre-Treatment Functional Assessment

• Bidimensional ultrasound evaluation of left ventricular ejection fraction to detect cardiac abnormalities before anthracycline therapy 1, 3
• Pulmonary function tests to identify patients at increased risk of bleomycin-related complications 3
• Thyroid function assessment (TSH, FT3, FT4) and dental care in patients candidate to neck irradiation 1

First-Line Treatment Strategy

Early-Stage Disease (Stages I-II)

Combined modality therapy with ABVD chemotherapy followed by involved-field radiotherapy (30 Gy) is the standard approach for early-stage disease 2, as radiotherapy alone has been definitively shown to be inferior with significantly worse freedom from progression (70% vs 93% at 5 years) 1.

Risk Stratification for Early-Stage Disease

• Favorable early-stage: 2 cycles of ABVD followed by involved-site radiotherapy (ISRT) of 20 Gy 4
• Unfavorable early-stage: 4 cycles of ABVD followed by ISRT of 30 Gy 4
• Unfavorable features include bulky mediastinal mass, extranodal disease, high ESR, ≥3-4 involved nodal sites, and B symptoms 5

Advanced-Stage Disease (Stages III-IV)

Full-term chemotherapy with ABVD (typically 6-8 cycles) is recommended for advanced-stage disease 2, 4. In 2025, brentuximab vedotin plus AVD (BV-AVD) for 6 cycles has emerged as the standard of care for advanced-stage disease, while ABVD remains a viable option in elderly patients due to its more favorable tolerability profile 4.

Adjuvant radiotherapy in patients without initial bulk who achieved complete remission is not recommended, as this increases toxicity without survival benefit 2.

Response Assessment and Treatment Adaptation

Interim PET Evaluation

• Early evaluation of response with FDG-PET scan after 2-4 cycles of chemotherapy is recommended to guide treatment modifications 2, 5
• Response is assessed using the Deauville 5-point scale, with scores 1-3 considered PET-negative 1, 6
• PET-negative patients (Deauville 1-3) after 2 cycles can continue with standard ABVD and potentially avoid radiotherapy in bulky disease 6
• PET-positive patients (Deauville 4-5) may require treatment intensification 6

Critical Pitfall to Avoid

Never use radiotherapy alone for early-stage disease, as combined modality therapy has proven superior survival outcomes with 3-year progression-free survival of 93% versus 70% with radiotherapy alone 2, 1.

Management of Relapsed or Refractory Disease

Standard Salvage Approach

High-dose chemotherapy followed by autologous hematopoietic stem cell transplant is the standard of care for patients younger than 60-65 years with relapsed or refractory disease 1, 2. This approach achieves 3-year event-free survival of 53% compared to 10% with conventional-dose therapy 1.

Second-Line Chemotherapy Options

• Non-cross-resistant regimens such as IGEV (ifosfamide, gemcitabine, vinorelbine), DHAP (dexamethasone, high-dose cytarabine, cisplatin), or ICE (ifosfamide, carboplatin, etoposide) should be used for debulking before autologous transplant 1
• These regimens are administered to chemosensitive patients before proceeding to high-dose therapy 1

Allogeneic Transplantation

• Allogeneic stem cell transplant with reduced-intensity conditioning is recommended in patients relapsing after autologous transplant 1
• Peripheral blood stem cells are preferred to bone marrow 1
• HLA-identical or partially identical family donors should be screened, with unrelated donor search for patients without suitable family donors 1

Role of Radiotherapy in Salvage

• Radiotherapy (30-36 Gy) to residual nodal disease may be recommended in patients with very good partial response after salvage therapy with autologous transplant 1
• Radiotherapy can be considered for limited residual disease in patients relapsing more than 3 years after first complete remission 1

Special Populations

Elderly Patients

• ABVD remains the preferred option in elderly patients due to its more favorable tolerability profile compared to intensified regimens 4
• Chemotherapy regimens more intensive than ABVD are not recommended in the elderly 1

Fertility Preservation

Reproductive counseling must be offered immediately to all patients of reproductive age before any treatment initiation, as chemotherapy and radiotherapy cause permanent fertility damage 5, 3. Fertility preservation measures should be taken before the initiation of therapy 1.

Long-Term Follow-Up Considerations

• Long-term follow-up after completion of treatment is essential to determine potential long-term effects, including second cancers and cardiovascular disease 1
• The 5-year overall survival for classical Hodgkin lymphoma now approaches 90%, with permanent remission rates of 80-90% in adolescents and young adults 5, 7
• Treatment strategies increasingly emphasize de-escalation and toxicity reduction in patients with favorable early response to minimize late effects 4