Classical Hodgkin LymphomaEdit

Classical Hodgkin lymphoma (CHL) is a cancer of the lymphatic system that principally affects B lymphocytes. It is distinguished by the presence of Reed-Sternberg cells within an inflammatory background. CHL accounts for a small fraction of all lymphomas but is notable for a high cure rate with modern treatment. The disease tends to present in two age peaks: in early adulthood and in later life, though it can occur at any age. Symptoms often include painless swelling of lymph nodes, usually in the neck or chest, and may be accompanied by fevers, night sweats, or weight loss. Because the condition is relatively uncommon and the symptoms can mimic infections, accurate diagnosis depends on tissue biopsy and expert staging. Hodgkin lymphoma Reed-Sternberg cell B cell Epstein-Barr virus

CHL is a highly treatable malignancy when detected and managed properly. With current regimens, long-term survival is common, especially in early-stage disease, and many patients are cured. The clinical course depends on stage at diagnosis, patient age, and comorbidity, but advances in imaging, chemotherapy, and radiotherapy have dramatically improved outcomes over the past several decades. In relapsed or refractory cases, salvage chemotherapy and autologous stem cell transplantation offer potential cures, while newer targeted therapies and immunotherapies are expanding options for difficult-to-treat disease. Ann Arbor staging PET-CT Autologous stem cell transplantation Brentuximab vedotin Nivolumab Pembrolizumab

Pathophysiology and classification

CHL is a malignancy arising from B cells in the lymphatic system. The hallmark cellular feature is the malignant Reed-Sternberg cell, typically CD30-positive and CD15-positive with weak expression of the B-cell marker PAX5. The tumor is unusual in that the neoplastic cells are a minority within a rich inflammatory microenvironment composed of T cells, eosinophils, macrophages, and other reactive cells. The disease is categorized under the umbrella of Hodgkin lymphoma, but the classical form (Classical Hodgkin lymphoma) has several subtypes that diverge in morphology and clinical behavior. The main subtypes include nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted forms. Reed-Sternberg cell CD30 CD15 PAX5 Nodular sclerosis Hodgkin lymphoma Mixed cellularity Hodgkin lymphoma Lymphocyte-rich Hodgkin lymphoma Lymphocyte-depleted Hodgkin lymphoma

A substantial proportion of CHL cases are associated with Epstein-Barr virus (EBV), particularly in certain age groups and geographic regions. The EBV connection appears to influence tumor biology and may have implications for etiology and prognosis in some patients. The exact role of EBV varies by subtype and population. Epstein-Barr virus

Epidemiology and risk factors

CHL shows a bimodal age distribution, with peaks in young adulthood and later life. Males are slightly more commonly affected than females in many populations. The disease is relatively uncommon compared with other cancers, but it is one of the most curable forms of lymphoma when treated appropriately. Compared with other segments of the population, incidence can differ by geography and race, with higher reported rates in some white populations in Western countries and variations in EBV association across groups. Risk factors include a history of EBV infection in certain settings and, in some analyses, familial predisposition. Hodgkin lymphoma Epstein-Barr virus Staging (cancer)

Diagnosis and staging

Diagnosis rests on biopsy of an affected node demonstrating Reed-Sternberg cells within the characteristic inflammatory milieu. Imaging and laboratory studies support staging and treatment planning. Typical presenting features include painless regional lymphadenopathy, mediastinal widening on chest imaging, and B symptoms (fever, drenching night sweats, unintended weight loss). Staging uses the Ann Arbor system (with Cotswold refinement) to classify disease by extent and spread, with stages I through IV describing progressively widespread involvement. Modern practice relies heavily on functional imaging with PET-CT to assess nodal involvement and to monitor response during therapy. In many patients, bone marrow biopsy is no longer mandatory for initial staging, depending on risk factors and institutional guidelines. Reed-Sternberg cell Ann Arbor staging PET-CT Staging (cancer) Hasenclever score

Prognostic tools, such as the Hasenclever International Prognostic Score (IPS) for advanced-stage disease, help guide treatment intensity. Deauville scoring on PET scans after initial cycles of therapy provides a robust method to adapt treatment in real time, potentially sparing patients from excessive toxicity while maintaining high cure rates. Hasenclever score Deauville five-point scale

Treatment

The goal of CHL treatment is to achieve durable remission with the least long-term toxicity. Treatment strategies balance immediate disease control with the risk of late adverse effects, particularly in patients treated at a young age.

Early-stage disease (Stage I–II): In many patients, a combination of chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for a limited number of cycles, followed by involved-site radiotherapy (ISRT), yields high cure rates. The role of radiotherapy is tailored to minimize long-term toxicity, and in some PET-responsive patients, chemotherapy alone may be sufficient. ABVD remains a standard regimen, with components each serving a purpose in achieving remission. ABVD chemotherapy Doxorubicin (Adriamycin) Bleomycin Vinblastine Dacarbazine Radiation therapy Involved-site radiotherapy
Advanced-stage disease (Stage III–IV) and high-risk early-stage cases: regimens often start with ABVD or alternative approaches such as escalated BEACOPP in select centers, depending on risk stratification and contributor factors. BEACOPP escalated involves a more intensive chemotherapy backbone and may improve progression-free outcomes in some populations, but it carries higher toxicity, including hematologic toxicity and fertility considerations. Treatment choice is guided by trial data, patient comorbidity, and preferences. BEACOPP escalated ABVD chemotherapy
Relapsed or refractory disease: For patients who relapse after initial therapy or do not respond adequately, options include salvage chemotherapy followed by autologous stem cell transplantation when feasible. Additional therapies include targeted agents and immunotherapies that have shown activity in CHL, especially in relapsed settings. Autologous stem cell transplantation Relapsed Hodgkin lymphoma Brentuximab vedotin Nivolumab Pembrolizumab
Targeted and immune therapies: Brentuximab vedotin (BV) has activity in CHL and has been studied in various settings, including first-line and salvage therapy. Immune checkpoint inhibitors such as nivolumab and pembrolizumab also demonstrate meaningful activity in relapsed disease. The use of BV-AVD or BV-AD in first-line regimens reflects evolving practice patterns and cost considerations. These approaches aim to balance cure rates with long-term toxicity and quality of life. Brentuximab vedotin Nivolumab Pembrolizumab
Fertility, cardiovascular, and secondary cancer considerations: Modern CHL management emphasizes minimizing late effects, particularly in patients treated with chest irradiation or alkylating regimens. Fertility preservation discussions, breast cancer risk reduction in survivors, and long-term surveillance for cardiovascular disease and secondary malignancies are important components of care. Fertility preservation Secondary cancer Cardiovascular disease

Prognosis and survivorship

With appropriate therapy, long-term remission and survival are common, especially for patients with limited-stage disease. Five-year survival rates in modern cohorts exceed the 90 percent mark for many early-stage patients and remain substantial in advanced stages, though they vary by stage, biology, and patient health. Survivors may experience late effects from treatment, including risks of secondary cancers, cardiovascular disease, thyroid dysfunction, infertility, and pulmonary toxicity, depending on the modalities used. Lifelong follow-up with primary care and oncology teams is standard to monitor for relapse and manage late toxicities. Survival rate Long-term effects of cancer treatment Secondary cancer Cardiovascular disease

Controversies and debates

Debates surrounding CHL treatment reflect balancing cure rates with long-term toxicity and cost.

De-escalation versus escalation of therapy: A persistent question is whether radiotherapy can be omitted in selected patients who achieve a complete metabolic response after chemotherapy, thereby reducing long-term risks of breast and other secondary cancers and cardiovascular disease. PET-guided strategies aim to tailor intensity to response, but real-world implementation varies. Proponents argue this approach preserves cure rates while limiting late toxicity; critics worry about the risk of undertreatment in subsets of patients. PET-CT Deauville score Involved-site radiotherapy
Use of radiotherapy: ISRT reduces relapse in many early-stage patients but increases cumulative exposure to normal tissues, which translates into lifelong toxicity risks. The conservative path emphasizes minimizing exposure, while others argue for targeted radiotherapy to consolidate remission and improve long-term outcomes. Radiation therapy
First-line novel agents and cost: Trials like those examining brentuximab vedotin in first-line regimens show potential for higher cure rates or reduced exposure to certain toxicities, but at substantially higher cost and with distinct toxicity profiles (e.g., neuropathy). Whether such regimens should become standard depends on cost-effectiveness analyses, healthcare system capabilities, and long-term outcome data. Brentuximab vedotin ECHELON-1 trial
Access and outcomes: Disparities in access to cutting-edge therapies and high-quality imaging can influence outcomes. In some settings, cost containment and patient adherence intersect with the real-world effectiveness of regimens, making streamlined, evidence-based protocols essential for maintaining high cure rates without overburdening patients or systems. Health disparities
Perspective on policy and practice: Advocates for cost-conscious care emphasize maximizing value—delivering the best available cures while avoiding unnecessary toxicities and overly expensive, marginally beneficial options. Critics sometimes argue that delaying advanced therapies can hinder outcomes for some patients. In this space, the emphasis is on evidence, patient-centered decision-making, and responsible stewardship of resources to deliver reliable, high-quality care. Evidence-based medicine