Journal: Blood advances
This study reports outcomes of reduced-intensity haploidentical bone marrow transplantation (BMT) using post-transplant cyclophosphamide in patients with severe sickle cell disease, after increasing the total body irradiation dose from 200 to 400 cGy to improve engraftment.
Key points:
- Population: 43 patients with sickle cell disease, age 2–70 years (median 23); most (79%) had ≥2 indications for transplant and all had ≥2 SCD comorbidities, reflecting a high-risk group.
- Conditioning regimen: Antithymocyte globulin, fludarabine, cyclophosphamide, and single-fraction 400 cGy total body irradiation.
- GVHD prophylaxis: Post-transplant cyclophosphamide, mycophenolate mofetil, and sirolimus.
Outcomes:
- Engraftment and disease control:
- Disease-free survival at 2 years: 94.5% (95% CI, 0.87–1.0).
- Graft failure: 2 patients (5%).
- Survival:
- 5-year overall survival: 95.5% (95% CI, 0.87–1.0) at median follow-up of 2.43 years.
- Late deaths: Two deaths at 2.5 and 6 years post-transplant.
- GVHD and toxicity:
- Grade 3–4 acute GVHD: 2.4% (95% CI, 0–0.07).
- Moderate–severe chronic GVHD: 7.3% (95% CI, 0–0.15).
- Median time to stop immunosuppression: 354 days.
- Fertility signal:
- Among 27 female patients, 12 had return of menses and/or normalization of gonadal function, suggesting potential fertility preservation with this reduced-intensity approach.
Overall, the 400 cGy RIC haploidentical platform with PTCy appears to offer high rates of durable engraftment, excellent survival, low GVHD incidence, and possible fertility preservation, thereby meaningfully expanding curative transplant options for patients with severe sickle cell disease, including those without matched related donors.