Is high‑dose chemotherapy (HDCT) with autologous stem‑cell transplantation (ASCT) curative for a fit patient under 65 years old with relapsed classical Hodgkin lymphoma who has achieved at least a partial remission after salvage chemotherapy?

High-Dose Chemotherapy with ASCT in Relapsed Classical Hodgkin Lymphoma

For a fit patient under 65 years old with relapsed classical Hodgkin lymphoma who has achieved at least partial remission after salvage chemotherapy, high-dose chemotherapy with autologous stem cell transplantation is the standard of care and offers the only potentially curative approach, with 3-year event-free survival of 53-55% compared to only 10-34% with conventional chemotherapy alone. 1

Evidence for Curative Potential

The curative potential of HDCT with ASCT is supported by two landmark randomized controlled trials that directly compared this approach to conventional-dose chemotherapy:

• British National Lymphoma Investigation (BNLI) trial: Patients receiving high-dose BEAM with ASCT achieved 53% actuarial 3-year event-free survival versus only 10% with conventional-dose mini-BEAM alone 1

• European Blood and Marrow Transplantation (EBMT) trial: Freedom from progression was significantly higher in the BEAM+ASCT group at 55% versus 34% with conventional chemotherapy 1

Critical caveat: Neither trial demonstrated an overall survival advantage for the transplant group, though event-free survival was dramatically superior 1. This means ASCT significantly delays disease progression and extends disease-free periods, but does not guarantee cure for all patients.

Grade A Recommendation

Patients younger than 60-65 years with relapsed disease or refractory to first-line therapy should receive second-line chemotherapy for debulking, followed—in chemosensitive patients—by high-dose chemotherapy and infusion of autologous stem cells from peripheral blood or bone marrow [Grade A recommendation]. 1

Prognostic Factors That Determine Success

The likelihood of achieving durable remission with ASCT depends critically on:

• Chemosensitivity to salvage therapy: Achieving FDG-PET negativity (complete metabolic response) after salvage chemotherapy is the single most important predictor of post-transplant outcomes 2, 3

• Timing of relapse: Early relapse (within 12 months) has significantly worse prognosis than late relapse, but ASCT remains indicated 1, 2

• Disease burden at transplant: Patients achieving complete remission prior to HDCT have significantly higher 4-year overall survival (78.4% vs 31.3% for partial remission) 4

• Response to initial salvage: Patients proceeding directly to transplantation with minimal disease after first relapse achieved 90% failure-free survival at 5 years 5

Long-Term Outcomes

Real-world data demonstrate:

• 5-year actuarial survival: 51% overall, with failure-free survival of 40% 5

• 4-year progression-free survival: 71.7% when ASCT consolidates response to salvage therapy 4

• Durable complete remissions: 75% of patients achieving CR after the full treatment sequence maintained durable remissions 4

When ASCT May Not Be Curative

ASCT has limited curative potential in:

• Primary refractory disease (progression within 3 months of treatment completion): This carries the worst prognosis with significantly lower response rates and shorter overall survival 6

• Chemotherapy-resistant disease: Patients who fail to achieve at least partial remission to salvage therapy have poor outcomes with ASCT 3, 7

• Multiple relapses: More than 50% of patients will experience relapse following ASCT, requiring additional therapies 4

Post-ASCT Consolidation for High-Risk Patients

For patients with early relapse (within 12 months) or primary refractory disease, brentuximab vedotin consolidation after ASCT is now standard, as randomized trials showed improved tumor control in these high-risk subgroups. 6

Alternative Options After ASCT Failure

If ASCT fails or the patient relapses post-transplant:

• Brentuximab vedotin: Overall response rate of 75% in post-ASCT relapse 2

• Anti-PD-1 antibodies (nivolumab or pembrolizumab): Effective for multiply relapsed disease 2, 6

• Allogeneic stem cell transplantation: Recommended for young, chemosensitive patients in good condition after careful risk-benefit evaluation, using reduced-intensity conditioning 1

Bottom Line on Curative Potential

HDCT with ASCT is potentially curative but not universally so. Approximately 40-55% of patients achieve durable event-free survival at 3-5 years, which represents the best available outcome for relapsed Hodgkin lymphoma in this age group 1, 5. The procedure offers significantly superior disease control compared to any conventional chemotherapy approach, making it the definitive standard of care for chemosensitive relapsed disease in fit patients under 65 1.