Initial Treatment for Hodgkin Lymphoma
The initial treatment for Hodgkin lymphoma is risk-stratified based on stage and prognostic factors, with ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) forming the backbone of therapy, combined with involved-field radiotherapy for early-stage disease, while advanced-stage disease requires 6-8 cycles of ABVD or escalated BEACOPP in younger patients. 1
Risk Stratification
Before initiating treatment, patients must be allocated to one of three risk groups based on Ann Arbor staging and specific risk factors 1:
- Early favorable: Stage I-II without risk factors 1
- Early unfavorable: Stage I-II with risk factors (large mediastinal mass >1/3 horizontal chest diameter, extranodal disease, ESR >50 with B symptoms or >30 without, ≥3 involved lymph node areas) 1
- Advanced: Stage III-IV, or stage IIB with large mediastinal mass or extranodal involvement 1
Treatment by Risk Group
Early Favorable Disease (Stage I-II without risk factors)
Standard treatment consists of 2 cycles of ABVD followed by 30 Gy involved-field radiotherapy. 1 This approach is based on the German Hodgkin Study Group HD7 and HD10 trials, which demonstrated that 2 cycles of ABVD is not inferior to 4 cycles when combined with radiotherapy, while substantially reducing toxicity 1. The addition of chemotherapy to radiotherapy significantly reduces relapse rates compared to radiotherapy alone 1.
An alternative chemotherapy-only approach using 4-6 cycles of ABVD can be considered, though prospective randomized trial data supporting this approach remains limited 1.
Early Unfavorable Disease (Stage I-II with risk factors)
Standard treatment is 4 cycles of ABVD followed by 30 Gy involved-field radiotherapy. 1 This achieves tumor control and overall survival exceeding 85-90% at 5 years 1. The Italian Society of Hematology guidelines confirm that 4 cycles of ABVD followed by involved-field radiotherapy represents the standard for this intermediate-stage risk group 1.
Recent evidence demonstrates that 4 cycles of ABVD followed by involved-site radiotherapy (ISRT) produces excellent outcomes even in patients with bulky disease, with 6-year freedom from relapse of 100% and no deaths, suggesting that 6 cycles does not provide superior disease control 2.
Advanced-Stage Disease (Stage III-IV)
For patients under 60 years, 8 cycles of BEACOPP escalated is considered standard by the German Hodgkin Study Group, achieving superior outcomes with 96% overall response, 88% disease-free survival, and 92% overall survival at 5 years. 1 A 2014 network meta-analysis including 9,993 patients confirmed a 10% survival advantage at 5 years with BEACOPP escalated compared to ABVD 1.
However, due to significantly higher acute toxicity, 6-8 cycles of ABVD remains widely used internationally and is the standard regimen for patients over 60 years. 1 ABVD achieves long-term cure rates of 50-60% in advanced disease 1. The BEACOPP regimen should not be given to patients >60 years due to increased treatment-related mortality in this age group 1.
Additional radiotherapy to initial tumor bulks or residual disease <2.5 cm after chemotherapy is not generally recommended outside clinical trials 1. Larger residual tumors that are PET-positive should receive additional radiotherapy 1.
Special Populations
Lymphocyte Predominant Hodgkin Lymphoma (LPHL)
Stage I LPHL can be treated with involved-field radiotherapy (30 Gy) alone 1. Rituximab is an option for relapsed LPHL given the CD20-positive immunophenotype 1.
Patients with Multiple Comorbidities
For patients with chronic liver disease, acute kidney injury, and cardiomyopathy, modified ABVD without bleomycin followed by involved-site radiotherapy is recommended for limited/intermediate stage disease 3. Bleomycin should be completely omitted due to pulmonary toxicity risk in patients with compromised organ function 3. BEACOPP is absolutely contraindicated in the setting of organ dysfunction 3.
Common Pitfalls
Avoid radiotherapy alone for early-stage disease: Multiple randomized trials (SWOG, GHSG HD7, EORTC H7 and H8) have definitively shown that combined modality therapy is superior to radiotherapy alone, with significantly better freedom from progression (93% vs 70% at 5 years in the SWOG trial) 1.
Do not use BEACOPP in elderly patients: Treatment-related mortality increases significantly in patients over 60 years receiving BEACOPP 1.
Monitor for bleomycin pulmonary toxicity: This complication occurs more frequently with 6 cycles compared to 4 cycles (31% vs 20%) 2, supporting shorter treatment duration when appropriate.