What are the characteristic features and treatment options for Hodgkin lymphoma?

Hodgkin Lymphoma: Characteristic Features and Treatment Options

Hodgkin lymphoma (HL) is a highly curable malignancy involving lymph nodes and the lymphatic system, characterized by Reed-Sternberg cells in classical Hodgkin lymphoma (CHL) or lymphocyte-predominant cells in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). 1

Types and Pathology

• HL is divided into two main types according to WHO classification: Classical Hodgkin Lymphoma (CHL) and Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) 1
• CHL accounts for approximately 95% of HL cases diagnosed in Western countries and is characterized by Reed-Sternberg cells in an inflammatory background 1
• CHL is further subdivided into four subtypes: nodular sclerosing, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted 1
• NLPHL (5% of cases) lacks Reed-Sternberg cells but contains lymphocyte-predominant cells ("popcorn cells") with a different immunophenotype (CD15-/CD30-/CD20+) compared to CHL (CD15+/CD30+/CD20-) 1
• Reed-Sternberg cells represent only 0.1-1% of the entire cell population, surrounded by a heterogeneous mixture of lymphocytes, histiocytes, eosinophils, plasma cells, and fibroblasts 1, 2

Epidemiology and Clinical Presentation

• HL has a bimodal age distribution with peaks at 15-30 years and after age 55 1
• Most patients (>60%) initially present with enlarged cervical lymph nodes 1
• B symptoms (fever, night sweats, weight loss) are important prognostic factors 1
• The disease is now curable in at least 80% of patients with modern treatment approaches 1

Diagnosis

• Diagnosis always requires a lymph node biopsy to identify Reed-Sternberg cells or lymphocyte-predominant cells 1, 3
• Immunophenotyping is essential to distinguish between CHL and NLPHL 1

Staging and Risk Assessment

• Staging is based on the Ann Arbor staging system with Cotswolds modification 1
• Required investigations include:
  • CT scans of neck, chest, and abdomen 1
  • Bone marrow aspiration and biopsy 1
  • PET/CT for accurate staging and response assessment 1
  • Blood tests including complete blood count, ESR, and chemistry panel 1
• Patients are classified into three risk groups:
  • Early-stage favorable (stage I-II without risk factors) 1
  • Early-stage unfavorable (stage I-II with risk factors such as bulky mediastinal disease, B symptoms, elevated ESR, multiple nodal sites) 1
  • Advanced-stage disease (stage III-IV) 1
• The International Prognostic Score (IPS) helps determine prognosis for patients with advanced disease 1

Treatment Approaches

Early-Stage Favorable Disease

• Standard treatment is combined modality therapy with 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by 30 Gy involved-field radiotherapy (IF-RT) 1
• This approach results in excellent long-term outcomes with cure rates exceeding 90% 1

Early-Stage Unfavorable Disease

• Standard treatment is 4 cycles of ABVD followed by 30 Gy IF-RT 1
• For patients under 60 years eligible for more intensive treatment, 2 cycles of BEACOPPescalated followed by 2 cycles of ABVD and 30 Gy IF-RT may provide superior freedom from treatment failure 1

Advanced-Stage Disease

• Treatment options include:
  • 6-8 cycles of ABVD with radiotherapy limited to residual masses 1
  • 8 cycles of BEACOPPescalated for patients under 60 years, followed by radiation to residual disease >1.5 cm 1
  • BEACOPPescalated provides superior freedom from treatment failure and overall survival compared to ABVD but with increased toxicity 1
• PET/CT is used to assess treatment response using the Deauville criteria (5-point scale) 1
• Patients older than 60 should receive 6-8 cycles of ABVD rather than BEACOPP due to increased toxicity in this age group 1

Relapsed or Refractory Disease

• High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care 1
• Salvage regimens such as DHAP, IGEV, or ICE are used to reduce tumor burden and mobilize stem cells prior to ASCT 1
• Brentuximab vedotin, a CD30-directed antibody-drug conjugate, has shown encouraging results in relapsed/refractory disease 1, 3
• Immune checkpoint inhibitors are an option for patients who fail ASCT or are ineligible 3

Response Assessment and Follow-up

• PET/CT is essential for response assessment using the Deauville criteria 1
• Long-term follow-up is crucial due to potential late effects of treatment 1, 3
• The risk of relapse decreases significantly after 2 years of event-free survival 4

Treatment Complications and Considerations

• Long-term complications include secondary malignancies, cardiovascular disease, and infertility 1, 3
• Fertility preservation should be offered to young patients prior to treatment 1
• Treatment selection must balance efficacy with potential long-term toxicity 1, 3