What is the cure rate of allogeneic (allo) hematopoietic stem cell transplant in follicular lymphoma?

Allogeneic Stem Cell Transplantation Cure Rate in Follicular Lymphoma

Allogeneic stem cell transplantation (allo-SCT) offers a potential cure rate of 76-85% at 4-8 years in patients with follicular lymphoma, though it carries significant treatment-related mortality risks of 15-20%. 1, 2, 3

Efficacy of Allogeneic Transplantation in Follicular Lymphoma

• Allogeneic transplantation demonstrates excellent long-term disease control with progression-free survival (PFS) rates of 76% at 4 years and overall survival (OS) rates of 76-85% at 4-8 years 3, 2
• The curative potential comes from the graft-versus-lymphoma (GVL) effect, which can lead to durable remissions and potential cure 2, 4
• Most studies show survival curves reaching a plateau at 12-24 months post-transplantation, suggesting curative potential 1
• Non-relapse mortality (NRM) is approximately 15% at 4 years, with higher rates in unrelated donor transplants (22%) compared to sibling donor transplants (8%) 1, 3

Conditioning Regimens and Outcomes

• Reduced-intensity conditioning (RIC) regimens have largely replaced myeloablative conditioning to reduce toxicity while maintaining efficacy 4
• Fludarabine-based regimens are commonly used, with the MD Anderson protocol (fludarabine, cyclophosphamide, and rituximab) showing 85% disease-free survival at 8 years with only 10% transplant-related mortality 2
• T-cell depletion approaches using alemtuzumab have shown excellent outcomes with low rates of chronic graft-versus-host disease (GVHD) and good disease control 3
• The conditioning regimen choice impacts treatment-related mortality but disease status at transplant remains the most significant factor affecting outcomes 4

Patient Selection and Timing

• Allo-SCT is recommended for young (<65 years old) fit patients who have relapsed after or are refractory to previous therapies including autologous stem cell transplantation (ASCT) 1, 5
• Chemosensitivity prior to transplant is a critical factor for success, with significantly better outcomes in patients with chemotherapy-sensitive disease 4
• Patients with chemotherapy-refractory disease have higher treatment-related mortality and recurrence rates, though some may still be cured, particularly with myeloablative transplants 4

Complications and Management

• Acute GVHD grade 2-3 occurs in approximately 13% of patients 3
• Extensive chronic GVHD occurs in 18-60% of patients depending on the conditioning regimen and GVHD prophylaxis method 3, 4
• Donor lymphocyte infusions (DLI) can effectively convert mixed chimerism to full donor chimerism, significantly reducing relapse risk 3
• For patients who relapse after transplantation, DLI can induce remission in approximately 77% of cases, with most responses being durable 3

Comparison with Autologous Transplantation

• While ASCT is effective for relapsed follicular lymphoma with 10-year PFS of 46% and OS of 57%, it is not considered curative for most patients 6
• ASCT is recommended for younger patients (<65 years) who relapse within 12 months of frontline chemoimmunotherapy and achieve response to reinduction therapy 5
• Allo-SCT is superior to ASCT in preventing relapse but carries higher treatment-related mortality 4
• For patients who relapse after ASCT, allo-SCT offers the only potential curative approach 1, 5

Practical Considerations

• Patient age, performance status, and comorbidities are more predictive of transplant outcomes than the specific conditioning regimen used 4
• Transplant-related mortality increases significantly in patients over 50 years, even with reduced-intensity conditioning 1
• The risk-benefit assessment must consider the 15-20% treatment-related mortality against the potential for long-term disease-free survival 4
• Careful donor selection is important, with matched sibling donors showing better outcomes (90% PFS at 4 years) compared to unrelated donors (64% PFS) 3