HemaSphere | EHA Clinical Practice Guidelines for Hodgkin Lymphoma: Diagnosis, Treatment, and Follow-up

This study provides a systematic framework for precise staging and risk-adapted therapy in Hodgkin lymphoma, offering direct guidance for clinical strategies in lymphoma management.

 

Literature Overview

This article, 'Hodgkin lymphoma: EHA Clinical Practice Guidelines for diagnosis, treatment, and follow-up,' published in the journal HemaSphere, systematically addresses the diagnosis, staging, risk stratification, treatment options, and long-term follow-up strategies for Hodgkin lymphoma (HL). Based on the latest clinical evidence, the guidelines integrate the central role of PET/CT in staging and response assessment, and provide systematic recommendations for individualized treatment pathways across different risk groups. The article further differentiates treatment approaches between classical Hodgkin lymphoma (cHL) and nodular lymphocyte-predominant HL (NLPHL), emphasizing the importance of multidisciplinary collaboration and long-term toxicity management.

Background Knowledge

Hodgkin lymphoma is a malignant lymphoma of B-cell origin, primarily affecting young adults with a bimodal age distribution. Although cure rates are high, current treatment strategies still face challenges related to long-term toxicities (e.g., secondary malignancies, cardiovascular disease, pulmonary fibrosis) and salvage therapy after relapse. In cHL, despite the widespread use of regimens such as ABVD and eBEACOPP, balancing efficacy and toxicity remains a key bottleneck. For NLPHL, the integration of anti-CD20 antibodies (e.g., rituximab) has not been fully standardized due to its indolent nature and CD20 expression. This guideline addresses these gaps by integrating findings from recent randomized trials (e.g., HD17, SWOG S1826, ECHELON-1) and PET-guided strategies to optimize treatment pathways for both newly diagnosed and relapsed patients, reduce unnecessary exposure to chemotherapy and radiotherapy, and improve cure rates. The guidelines also specifically address the management of elderly patients and those unfit for intensive therapy, filling critical gaps between existing evidence and clinical practice.

 

 

Research Methods and Experiments

The author team, following evidence-based medicine principles, integrated data from multiple key randomized controlled trials (RCTs), including GHSG HD10, HD14, HD17, HD21, RAPID, H10F, H10U, SWOG S1826, and ECHELON-1. These studies employed PET/CT-guided staging and interim assessments, combining Ann Arbor staging with clinical risk factors (e.g., bulky mediastinal disease, B symptoms, elevated ESR) for risk stratification. The experimental designs compared the efficacy and toxicity of different chemotherapy regimens (e.g., ABVD vs. eBEACOPP vs. BrECADD vs. N-AVD) with or without radiotherapy. Key evidence includes: the HD17 study demonstrated that in early unfavorable cHL, radiotherapy can be omitted if interim PET is negative; SWOG S1826 showed N-IVD superiority over BV-AVD, particularly in elderly patients; ECHELON-1 supported the superiority of BrECADD in younger patients. Together, these data support a risk-adapted and PET-guided individualized treatment model.

Key Conclusions and Perspectives

• For early favorable cHL patients, 2 cycles of ABVD followed by 20Gy involved-site radiotherapy (IS-RT) achieves >90% 5-year PFS, supporting this as a standard approach to avoid overtreatment.
• In early unfavorable cHL (≤60 years), the '2+2' regimen (2 cycles eBEACOPP + 2 cycles ABVD) followed by PET-guided radiotherapy significantly improves disease control, with safe omission of radiotherapy in PET-negative patients.
• For advanced-stage cHL, BrECADD or N-IVD are preferred—BrECADD offers higher efficacy, while N-IVD has lower toxicity, allowing tailored selection based on patient characteristics.
• For relapsed/refractory cHL, PD-1 inhibitors combined with chemotherapy should be prioritized as salvage therapy, significantly improving complete metabolic response (CMR) rates and subsequently enhancing outcomes post-ASCT.
• In NLPHL, CD20-targeted therapy (e.g., rituximab) combined with chemotherapy or radiotherapy alone is the core strategy, whereas brentuximab vedotin (BV) and PD-1 inhibitors are ineffective, highlighting biological differences from cHL.
• Elderly patients (>60 years) should avoid bleomycin; N-IVD or A(B)VD+AVD regimens are recommended to reduce pulmonary toxicity risks.

Research Significance and Prospects

The guideline provides clear direction for drug development: future efforts should focus on reducing long-term toxicities of conventional chemotherapy, such as developing safer anti-CD30 antibody-drug conjugates or optimizing the timing of immune checkpoint inhibitor use. In clinical monitoring, dynamic PET/CT assessment has become standard, advancing response-adapted treatment strategies. Additionally, the guideline emphasizes monitoring for second malignancies, cardiovascular, and endocrine dysfunction during long-term follow-up, suggesting the need for standardized survivorship care pathways. For disease modeling, this guideline offers real-world treatment references for preclinical research, such as simulating post-relapse treatment responses in humanized mouse models.

 

 

Conclusion

This EHA clinical practice guideline provides a comprehensive, evidence-driven framework for the modern management of Hodgkin lymphoma. By integrating PET/CT-guided risk stratification and individualized therapy, it significantly improves cure rates while reducing long-term toxicities. The guideline clearly differentiates treatment pathways between cHL and NLPHL, highlights the therapeutic value of CD20 targeting in NLPHL, and offers practical strategies for elderly and relapsed patients. Its precise definition of radiotherapy indications, optimized chemotherapy selection, and systematic recommendations for long-term complication management collectively form the cornerstone of contemporary HL care. Future research should further explore biomarker-driven treatment decisions, such as dynamic monitoring of ctDNA or TARC, to achieve more precise individualization, ultimately transforming HL into a curable and low-burden chronic disease.

 

Dennis A Eichenauer, Marc André, Peter Borchmann, Joseé M Zijlstra, and Igor Aurer. Hodgkin lymphoma: EHA Clinical Practice Guidelines for diagnosis, treatment, and follow‐up. HemaSphere.