What are the considerations for allogenic (allogeneic) stem cell bone marrow transplantation in elderly patients with aplastic anemia?

Allogeneic Stem Cell Bone Marrow Transplantation in Elderly Patients with Aplastic Anemia

Allogeneic stem cell transplantation should be considered for selected elderly patients with aplastic anemia up to age 70 years, with reduced-intensity conditioning regimens preferred for those over 55 years of age. 1

Patient Selection Criteria

Age alone should not be an exclusionary factor for allogeneic stem cell transplantation (allo-SCT) in aplastic anemia. Instead, the following factors should guide decision-making:

• Comorbidity assessment: Hematopoietic Cell Transplantation Comorbidity Index should be used rather than chronological age 1
• Performance status: "Particularly fit" patients over 70 years may still be considered 1
• Disease severity: Higher-risk disease favors transplantation even in older patients
• Time from diagnosis: Early transplantation (≤6 months from diagnosis) is associated with better outcomes 2
• Donor availability: HLA-identical siblings or matched unrelated donors are preferred 1

Age-Specific Considerations

• Age 40-50 years: Outcomes similar to younger patients when using matched related donors; should proceed to transplant early 2
• Age 50-70 years: Increased non-relapse mortality but still beneficial in selected patients 1
• Age >70 years: Limited data; only consider in exceptionally fit individuals with no significant comorbidities 1

Donor Selection Hierarchy

1. HLA-identical siblings or single antigen mismatched siblings [Level I, A] 1
2. Matched unrelated donors [Level I, A] 1
3. Haploidentical donors [Level II, B] 1
4. Cord blood (less commonly used) [Level II, B] 1

Conditioning Regimens

The choice of conditioning regimen is critical for elderly patients with aplastic anemia:

• Age <55 years without comorbidities: Consider myeloablative conditioning [Level II, B] 1
• Age >55 years or with comorbidities: Reduced-intensity conditioning (RIC) is preferred 1
• Optimal regimens:
  • Fludarabine/cyclophosphamide/ATG shows excellent outcomes in matched sibling donor transplants 3
  • Cyclophosphamide/ATG is an alternative effective regimen 3

Pre-Transplant Considerations

• Iron overload management: Elevated labile plasma iron levels predict increased infection-related mortality; appropriate iron chelation should be administered before conditioning 1
• Timing: Early transplantation (within 6 months of diagnosis) is associated with better outcomes 2
• Pre-transplant therapy: Consider immunosuppressive therapy if transplant will be delayed 4

GVHD Prophylaxis

• Rabbit-derived ATG is associated with lower risk of grade II-IV acute GVHD compared to equine-derived ATG 3
• Standard GVHD prophylaxis typically includes cyclosporine and methotrexate 4
• Post-transplantation cyclophosphamide strategies may improve outcomes, particularly with alternative donors 5

Monitoring and Post-Transplant Care

• Close monitoring for infections, particularly in the first 100 days
• Vigilance for late effects including cataracts, thyroid disorders, joint problems, and therapy-related cancers 6
• Long-term follow-up for disease recurrence and transplant-related complications

Common Pitfalls to Avoid

• Delaying donor search: Begin HLA typing and donor search at diagnosis
• Overlooking comorbidities: Thorough assessment is essential as comorbidities impact outcomes more than age alone
• Excessive transfusions: Minimize transfusions pre-transplant when possible to reduce alloimmunization and iron overload
• Inappropriate conditioning: Using myeloablative conditioning in older patients increases transplant-related mortality
• Neglecting iron overload: Failure to address iron overload before transplant increases non-relapse mortality 1

Transplant outcomes have improved significantly over time, with survival rates ranging from less than 40% to more than 90% depending on patient and donor factors 6. For elderly patients who are not candidates for transplantation or who lack suitable donors, immunosuppressive therapy remains the primary alternative treatment approach 4.