What is the success rate of adult allogeneic (allo) bone marrow transplant for sickle cell disease?

Success Rate of Adult Allogeneic Bone Marrow Transplantation for Sickle Cell Disease

Allogeneic bone marrow transplantation in adults with sickle cell disease has demonstrated promising results with event-free survival rates of 82-88% at 2-3 years in recent clinical trials. 1, 2

Current Outcomes by Donor Type

Matched Sibling Donor (MSD) Transplants

• Highest success rates with overall survival around 95% and disease-free survival of 86-95% 3, 1
• Considered the gold standard donor source for SCD patients
• Lowest risk of graft rejection and graft-versus-host disease (GVHD)
• Unfortunately, only about 18% of SCD patients have an available MSD 3

Matched Unrelated Donor (MUD) Transplants

• Limited data specifically for SCD due to difficulty finding suitable donors
• In a multicenter pilot study, 5 adult patients received 8/8 HLA-matched unrelated donor transplants with similar outcomes to matched sibling recipients 1
• One-year event-free survival of 86% in combined MSD and MUD recipients 1

Haploidentical Transplants

• Recent advances show promising results with 2-year event-free survival of 88% and overall survival of 95% 2
• Higher risk of complications but expanding access to curative therapy
• Incidence of grade 3-4 acute GVHD was 4.8% and 2-year chronic GVHD rate was 22.4% 2

Factors Affecting Transplant Success

Age and Timing

• Historically better outcomes in younger patients
• Recent studies show improved outcomes in adults with event-free survival >80% 1, 2
• Earlier transplantation (pre-school age) recommended when possible to prevent organ damage 3

Conditioning Regimen

• Reduced toxicity regimens have improved outcomes in adults
• Common regimens include:
  • Busulfan (13.2 mg/kg), fludarabine (175 mg/m²), and thymoglobulin (6 mg/kg) 1
  • More complex regimens for haploidentical transplants including antithymocyte globulin, fludarabine, cyclophosphamide, thiotepa, and total body irradiation 2

Stem Cell Source

• Bone marrow is the recommended stem cell source for SCD patients 3
• Peripheral blood stem cells associated with higher risk of chronic GVHD 3
• Cord blood may be an option with low rejection rates and low risk of GVHD 3

Complications and Risks

Graft-versus-Host Disease

• Acute GVHD (grades II-III): approximately 18% in adult recipients 1
• Chronic GVHD: 22-27% in adult recipients 1, 2
• Severe chronic GVHD occurs in a small percentage of patients

Mortality

• Overall survival rates of 91-95% at 1-2 years in recent adult trials 1, 2
• Main causes of mortality include:
  • Intracranial hemorrhage
  • Severe GVHD
  • Infectious complications

Graft Failure

• Primary graft failure: rare but serious complication (4.8% in haploidentical transplants) 2
• Secondary graft failure may occur and sometimes requires a second transplant 1, 2

Patient Selection

Transplantation should be considered for SCD patients with:

• Stroke or CNS events lasting >24 hours
• Recurrent acute chest syndrome requiring hospitalization
• Recurrent vaso-occlusive pain (>2 episodes per year over several years)
• Impaired neuropsychological function with abnormal cerebral MRI
• Sickle lung disease, nephropathy, retinopathy, or osteonecrosis of multiple joints 3

Conclusion

Allogeneic bone marrow transplantation offers a potentially curative option for adults with sickle cell disease with increasingly favorable outcomes. The best results are seen with matched sibling donors, but recent advances in haploidentical transplantation are expanding access to this therapy. Patient selection, timing, conditioning regimen, and GVHD prophylaxis are critical factors in optimizing outcomes.