For a fit patient under 65 with relapsed classical Hodgkin lymphoma who achieved at least a partial remission after salvage chemotherapy and has adequate performance status and organ function, is autologous stem‑cell transplantation the recommended curative treatment?

Autologous Stem Cell Transplantation in Relapsed Classical Hodgkin Lymphoma

Yes, autologous stem cell transplantation (ASCT) is unequivocally the recommended curative treatment for fit patients under 65 with relapsed classical Hodgkin lymphoma who achieve at least partial remission after salvage chemotherapy. 1, 2

Evidence Supporting ASCT as Standard of Care

The superiority of high-dose chemotherapy followed by ASCT over conventional-dose therapy is established by two landmark randomized controlled trials that demonstrate dramatically improved disease control 1:

• British National Lymphoma (BNLI) trial: 3-year event-free survival was 53% with ASCT versus only 10% with conventional-dose chemotherapy 1, 2
• European Blood and Marrow Transplantation (EBMT) trial: Freedom from progression was 55% with ASCT versus 34% with conventional chemotherapy alone 1, 2

These data establish ASCT as a Grade A recommendation for patients younger than 60-65 years with relapsed or refractory disease who demonstrate chemosensitivity to salvage therapy. 1, 3

Critical Treatment Algorithm

Step 1: Salvage Chemotherapy for Debulking and Stem Cell Mobilization

Administer 2-3 cycles of platinum-based salvage chemotherapy using non-cross-resistant regimens 1, 2, 4:

• DHAP (cisplatin, high-dose cytarabine, dexamethasone) 1, 2
• ICE (ifosfamide, carboplatin, etoposide) 1, 2
• IGEV (ifosfamide, gemcitabine, vinorelbine) 1, 2

The dual purpose is achieving maximum tumor reduction (debulking) and efficiently mobilizing peripheral blood progenitor cells for subsequent autologous rescue 1, 2. No randomized studies demonstrate superiority of one regimen over another 1.

Step 2: Response Assessment with PET-CT

Perform FDG-PET scan after salvage chemotherapy to assess chemosensitivity—this is the single most important predictor of post-transplant outcomes. 1, 2, 4

• Goal: Achieve complete metabolic response (PET-negative status, Deauville score 1-3) 2, 4
• Chemosensitive disease (at minimum partial response) is required to proceed to ASCT 1, 5

Step 3: Proceed Immediately to ASCT

For chemosensitive patients, proceed directly to high-dose chemotherapy (typically BEAM regimen: carmustine, etoposide, cytarabine, melphalan) followed by autologous stem cell infusion without delay 1, 2, 4, 3.

The American Society of Transplantation and Cellular Therapy recommends ASCT consolidation after salvage therapy in the first relapse setting for patients with chemotherapy-sensitive disease in complete response. 3

Age-Specific Considerations

Your patient's age (under 65) places them squarely within the recommended age range for ASCT. 1, 2 Guidelines specifically state that patients younger than 60-65 years with relapsed disease or refractory to first-line therapy should receive salvage chemotherapy followed by ASCT in chemosensitive patients 1. Age alone should NOT exclude this patient from transplantation 2.

Important Caveats and Pitfalls

Conventional Chemotherapy Has No Curative Potential

Conventional-dose chemotherapy has virtually no curative potential in patients with resistant or early relapsing Hodgkin lymphoma. 1 Do not accept conventional chemotherapy alone as definitive treatment for this patient 4.

Chemosensitivity is Mandatory

Do not proceed to ASCT if the patient remains PET-positive after salvage therapy. 4 For patients who fail to achieve chemosensitivity with first salvage regimen, consider alternating to a non-cross-resistant chemotherapy regimen or exploring novel agents (brentuximab vedotin, checkpoint inhibitors) to improve response before ASCT 4, 3.

Overall Survival Benefit Not Demonstrated

While both randomized trials showed dramatic improvements in event-free survival, neither demonstrated an overall survival advantage for the transplant group 1. This likely reflects effective salvage options after relapse post-ASCT, but does not diminish the importance of achieving durable disease control.

Modern Enhancements to ASCT Strategy

Pre-ASCT Salvage with Novel Agents

The American Society of Transplantation and Cellular Therapy now recommends preferred use of pre-HCT salvage therapy regimens incorporating novel agents (brentuximab vedotin or checkpoint inhibitors) 3. Recent data show that ASCT after anti-PD-1 therapy yields 18-month progression-free survival of 81% even in heavily pretreated, chemorefractory patients 6.

Post-ASCT Consolidation

Consider brentuximab vedotin consolidation after ASCT for high-risk patients (those with primary refractory disease, early relapse <12 months, or extranodal disease at relapse) 5, 7, 8. This has become standard practice based on randomized trial data showing improved tumor control 5.

If ASCT Fails or Patient Cannot Proceed

For patients who relapse after ASCT or cannot achieve chemosensitivity 2, 4:

• Brentuximab vedotin: Preferred single-agent option with 75% overall response rate 2, 4
• Anti-PD-1 antibodies (nivolumab or pembrolizumab): FDA-approved for multiply relapsed disease 2, 4
• Allogeneic stem cell transplantation: Consider in young, chemosensitive patients in good condition after careful risk-benefit evaluation 1, 3