From Fear to Cure: Hodgkin Lymphoma and the Importance of Awareness

Abdulrahman Al-Abdulmalek, MD.
Chief Hematology Fellow 
McGill university 
Montreal, Canada

Introduction

Cancer often carries an image of late-life illness, but not all cancers follow this pattern. Hodgkin lymphoma (HL), a highly curable malignancy, frequently strikes individuals in their twenties, and thirties; the very years when life is taking shape. For patients and families, hearing the diagnosis can be frightening. Yet the story of HL is also one of hope: when diagnosed early and treated appropriately, most patients achieve cure. This duality makes HL an important focus during Blood Cancer Awareness Month; a reminder that vigilance, timely diagnosis, and evidence-based therapy can transform outcomes.

Definition and Epidemiology

Classic Hodgkin lymphoma (cHL) is a B-cell–derived lymphoid neoplasm defined by the presence of malignant Hodgkin/Reed–Sternberg (HRS) cells within a background of reactive immune cells [2]. It accounts for about 10% of all lymphomas worldwide and 0.5% of all cancers [5].

The disease displays a bimodal age distribution, with one peak in young adulthood (ages 15–34) and a second, smaller peak in older adults. Subtype distribution varies: nodular sclerosis is most common in high-income countries, while mixed cellularity and lymphocyte-depleted subtypes are more frequent in resource-limited settings, often linked to Epstein–Barr virus (EBV) infection [2].

In Qatar, between 2013 and 2017, malignant lymphoma accounted for 414 cases; HL represented 21% of these. National registry data report a 3-year overall survival of 94% for HL, comparable or superior to international benchmarks [1]. According to GLOBOCAN 2022, there were 49 new HL cases in Qatar that year, making it the 11th most common cancer nationally and accounting for 2.8% of all new cancer diagnoses. The 5-year prevalence was estimated at 207 cases per 100,000 population [3].

Risk Factors

• Epstein–Barr virus (EBV): Detected in up to 70% of mixed cellularity and nearly all lymphocyte-depleted cases; more common in low-resource regions [2].
• Immunosuppression: HIV infection, post-transplant immunosuppression, and certain autoimmune conditions increase risk [6].
• Familial predisposition: Same-sex siblings of patients with HL have been reported to have up to a 10-fold higher risk of developing the disease, and monozygotic twins of HL patients have significantly increased risk compared with dizygotic twins [5,8]. Genetic susceptibility and abnormal immune responses also play an important role in pathogenesis [2].

Molecular Insights: HL develops in part because Reed–Sternberg cells learn to evade the immune system. Changes in chromosome 9p24.1 drive overexpression of PD-L1/PD-L2 and activate JAK2 signaling, while EBV infection and tumor-associated macrophages add to PD-L1 expression. These changes allow the tumor to hide from T-cells, but they also explain why PD-1 inhibitors work so well in HL, changing outcomes in relapsed and frontline disease [2,7].

Clinical Presentation and Diagnosis

HL is broadly divided into two main types: classic Hodgkin lymphoma (cHL), which represents about 90–95% of all cases, and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), which accounts for the remaining 5–10% [2]. In this article we will focus on cHL, given its predominance and distinct biology and management. Clinically, cHL often presents with painless lymphadenopathy, especially in the cervical and mediastinal regions. About 40% of patients experience systemic “B symptoms”: fever, drenching night sweats, and unexplained weight loss [2]. Other features include pruritus, fatigue, or rarely alcohol-induced pain at disease sites.

Diagnosis and staging are closely linked. Diagnosis requires excisional lymph node biopsy whenever feasible, as fine needle aspiration lacks sensitivity and architecture preservation. A core needle biopsy may be used in selected cases where excision is not possible [2]. Pathology demonstrates HRS cells with CD30 and CD15 positivity, weak PAX5, and absence of CD45. Staging evaluation involves PET-CT imaging, Ann Arbor classification, blood counts, ESR, and screening for HIV, hepatitis B and C, and in high-risk populations, tuberculosis. Bone marrow biopsy is reserved for unexplained cytopenias, or when staging information would influence management decisions [2].

We subcategorize HL into early-stage (I–II) and advanced-stage (III–IV) disease. Early-stage is further classified as favorable or unfavorable, depending on factors such as bulky mediastinal mass, involvement of three or more nodal sites, presence of B symptoms, or elevated ESR. Risk stratification systems like the German Hodgkin Study Group (GHSG) and European Organisation for Research and Treatment of Cancer (EORTC) refine these definitions, incorporating criteria such as age >50 years, ESR thresholds, and extranodal disease. This distinction is important because it guides treatment intensity and use of combined modality therapy. In advanced-stage disease, the International Prognostic Score (IPS) is applied to predict outcomes and tailor therapy [4,2].

Pre-treatment Evaluation

Before initiating chemotherapy, baseline assessments are crucial. An echocardiogram or cardiac function test is recommended to evaluate left ventricular ejection fraction prior to anthracycline exposure. Pulmonary function tests, particularly diffusion capacity, help assess risk before bleomycin therapy. In addition, fertility counseling and preservation options should be discussed with young patients, as some regimens may impair reproductive potential.

Treatment Approaches

Treatment of Hodgkin lymphoma is highly effective and stage-adapted, aiming to achieve cure while minimizing late toxicities. In early-stage favorable disease, combined-modality therapy with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) plus involved-site radiotherapy remains a cornerstone, with long-term overall survival above 95%. PET-adapted approaches allow therapy to be de-escalated or escalated according to interim response, and radiotherapy can sometimes be omitted to avoid long-term effects. Bleomycin may also be omitted in patients achieving an early complete metabolic response, to reduce pulmonary toxicity. In early-stage unfavorable disease, more intensive combined-modality regimens are typically used. Interim PET imaging guides therapy—for example, escalating to BEACOPP in those with inadequate response; helping to maximize cure rates while minimizing toxicity. These strategies achieve excellent results, with five-year overall survival exceeding 90% [2].

Advanced-stage (III–IV): Historically treated with ABVD, but newer regimens such as BV-AVD (brentuximab vedotin + AVD), BrECADD, and especially N-AVD (nivolumab + AVD) have reshaped practice. N-AVD has emerged as the preferred standard, achieving ~94% 1-year progression-free survival with less neurotoxicity compared with BV-AVD [7]. Interim PET-CT continues to guide escalation or de-escalation in this setting.

Survivorship and Follow-up

Because cure is expected in most cases, survivorship care is critical:

• Secondary malignancies: Breast cancer, lung cancer, leukemia (especially after radiation/alkylators).
• Cardiac disease: Due to anthracyclines and mediastinal
• Endocrine disorders: Hypothyroidism after neck irradiation; gonadal toxicity from
• Monitoring: Structured lifelong follow-up with cancer screening, cardiovascular risk reduction, endocrine monitoring, and fertility counseling [2].

Public Health in Qatar

Qatar’s National Cancer Strategy and registry-based surveillance integrate HL into standardized care pathways. Outcomes align with global standards, reflecting strong access to PET-CT, pathology, and evidence-based chemotherapy [1]. While there is no known primary prevention for HL, early diagnosis through public and healthcare provider awareness can significantly improve outcomes. In Qatar, outcomes for HL align with, and in some areas exceed, global benchmarks. A strong message for clinicians is clear: continued investment in awareness, early detection, individualized therapy, and structured survivorship programs will sustain these achievements and further reduce the long-term burden of disease.

Key Clinical Pearls

• General practitioners should stay vigilant and remember that cancer can affect the young. HL should be considered in the differential diagnosis when young patients present with B symptoms, as early suspicion and referral are key to timely detection and improved outcomes.
• Always obtain an excisional biopsy when possible.
• PET-CT is essential for both staging and response-adapted therapy.
• Interim PET guides de-escalation/escalation to minimize toxicity.
• Counsel young patients on fertility preservation before treatment.
• Survivorship planning is as important as initial therapy.

Conclusion

Hodgkin lymphoma represents one of oncology’s success stories: a cancer that once instilled fear now offers cure to most patients. With continued investment in early recognition, precision treatment, and survivorship care, Qatar and the wider MENA region can ensure that patients not only survive HL but thrive beyond it.

References

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