What is the recommended treatment and expected side effects for a patient with Classical Hodgkin Lymphoma (CHL) stage IIIB post-biopsy, specifically the ABVD (Adriamycin (doxorubicin), Bleomycin, Vinblastine, and Dacarbazine) regimen?

Treatment for Classical Hodgkin Lymphoma Stage IIIB

For stage IIIB classical Hodgkin lymphoma, the standard treatment is 6-8 cycles of ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine), with consideration for consolidative radiation therapy to bulky sites >5 cm based on interim PET response. 1

Primary Treatment Regimen

ABVD remains the established standard of care for advanced-stage Hodgkin lymphoma (stage III-IV) based on landmark trials demonstrating superior efficacy with less myelotoxicity compared to older regimens. 1 The NCCN guidelines recommend 6-8 cycles of ABVD for stage III-IV disease, with interim PET scanning after 2-4 cycles to guide treatment decisions. 1

ABVD Dosing Schedule

• Doxorubicin (Adriamycin): 25 mg/m² IV on days 1 and 15 2
• Bleomycin: 10 units/m² IV on days 1 and 15 1
• Vinblastine: 6 mg/m² IV on days 1 and 15 2
• Dacarbazine: 375 mg/m² IV on days 1 and 15 3

Each cycle is 28 days, with chemotherapy administered on days 1 and 15. 1

Response-Adapted Approach

After 2-4 cycles of ABVD, interim PET scanning using the Deauville 5-point scale determines subsequent management: 1

• Deauville score 1-3: Continue ABVD to complete 6-8 cycles total; consider ISRT (30 Gy) for initial sites >5 cm 1
• Deauville score 4: Continue ABVD to complete 6-8 cycles with ISRT 1
• Deauville score 5: Biopsy recommended; if positive, manage as refractory disease 1

Alternative Regimens

Escalated BEACOPP

For patients under age 60 with high-risk disease (International Prognostic Score ≥3), escalated BEACOPP may be considered, though it carries significantly higher toxicity. 1 The HD9 trial demonstrated superior 10-year freedom from treatment failure (82% vs 64%) and overall survival (86% vs 75%) compared to COPP-ABVD, but this comes at the cost of increased acute toxicity and secondary malignancies. 1

BEACOPP is contraindicated in patients over age 60 due to excessive toxicity. 1

Stanford V

Stanford V (12 weeks) followed by ISRT (30 Gy) to sites >5 cm is an alternative option, though the E2496 trial showed no significant difference in overall survival compared to ABVD. 1 Among high-risk patients (IPS ≥3), ABVD demonstrated superior 5-year freedom from progression (67% vs 57%, P=0.02). 1

Expected Side Effects by Drug

Doxorubicin (Adriamycin)

• Cardiotoxicity: Dose-dependent cardiomyopathy; baseline echocardiogram or MUGA scan required before treatment 1, 4
• Myelosuppression: Neutropenia, thrombocytopenia, anemia 1
• Nausea/vomiting: Common, manageable with antiemetics 1
• Alopecia: Universal, reversible 1
• Red urine discoloration: Harmless, expected within 1-2 days of administration 1

Bleomycin

Bleomycin-induced pulmonary toxicity (BPT) is the most critical concern, occurring in 5-10% of patients and potentially fatal. 1 Risk factors include:

• Age >40 years 1
• Cumulative dose >400 units 1
• Concurrent or prior chest radiation 1
• Pre-existing lung disease 1
• Concurrent use of G-CSF (growth factors should NOT be routinely used with ABVD) 1

Baseline pulmonary function tests and monitoring for dyspnea, cough, or infiltrates on chest imaging are essential. 1 Bleomycin should be discontinued immediately if pulmonary toxicity develops. 1

Vinblastine

• Peripheral neuropathy: Sensory > motor, typically grade 1-2, dose-limiting 1, 2
• Constipation: Due to autonomic neuropathy; prophylactic bowel regimen recommended 2
• Myelosuppression: Primarily neutropenia 2
• Alopecia: Common 2

Dacarbazine

• Nausea/vomiting: Most common side effect (>85%), requires aggressive antiemetic prophylaxis 3
• Myelosuppression: Neutropenia and thrombocytopenia, typically nadir at 3-4 weeks 3
• Flu-like symptoms: Fever, myalgias, malaise 3
• Photosensitivity: Sun protection essential 3
• Hepatotoxicity: Transient transaminase elevation 3

Critical Management Considerations

Growth Factor Use

Routine prophylactic G-CSF is NOT recommended with ABVD, as it may increase the risk of bleomycin pulmonary toxicity and does not improve overall survival. 1 Two separate studies confirmed ABVD can be safely administered at full-dose intensity without growth factor support. 1

Fertility Preservation

ABVD is rarely associated with permanent infertility, unlike BEACOPP which causes immediate and permanent infertility in most patients. 1, 4 However, fertility counseling and consideration of sperm banking or oocyte preservation should be discussed before treatment initiation. 1, 4

Infection Risk

Myelosuppression is the most common side effect of chemotherapy, increasing infection risk. 1 Pneumococcal, meningococcal, and H. influenzae vaccinations are recommended every 5 years for patients receiving splenic radiation or splenectomy. 1

Common Pitfalls to Avoid

1. Do not use G-CSF routinely with ABVD - increases pulmonary toxicity risk 1
2. Monitor pulmonary symptoms vigilantly - bleomycin toxicity can be fatal if not recognized early 1
3. Avoid high-flow oxygen during anesthesia - increases bleomycin lung injury risk 1
4. Ensure adequate antiemetic prophylaxis - dacarbazine causes severe nausea in >85% of patients 3
5. Baseline cardiac assessment mandatory - doxorubicin cardiotoxicity is cumulative and irreversible 1, 4

Prognosis

With ABVD treatment, 5-year overall survival for stage III-IV disease is 82-85%, with complete remission rates of 76-80%. 1, 4 The presence of B symptoms (which defines stage IIIB) is incorporated into risk stratification but does not fundamentally alter the treatment approach. 1