Haploidentical transplant shows 79% two-year event-free survival in children with sickle cell disease

BMT CTN 1507 (NCT03263559) enrolled children aged 5–14.99 years with severe sickle cell disease, including qualifying neurological events, severe acute chest syndrome or recurrent vaso-occlusive pain. Forty-one participants enrolled at 18 centers; 39 proceeded to transplant. Most had hemoglobin SS disease (38/39), and 32/39 received grafts from donors mismatched at four HLA loci. The regimen used reduced-intensity conditioning and post-transplant cyclophosphamide, sirolimus and mycophenolate for graft-versus-host disease prophylaxis.

At two years, event-free survival was 79.3% (95% CI, 62.8%–89.1%) and overall survival was 94.5% (95% CI, 79.7%–98.6%). Predicted FEV1 increased from 79.5% to 95.7% (p=0.014); estimated glomerular filtration rate fell from 174 to 127 mL/min/1.73 m² (p<0.001), which the investigators interpreted as resolution of hyperfiltration. Serial MRI showed no new or progressive cerebral infarcts among the 22 participants assessed.

Graft failure and graft-versus-host disease were associated with lower event-free survival. The single-arm phase II design and small cohort limit conclusions about comparative effectiveness. The findings support further evaluation of haploidentical transplantation for children without a matched sibling donor, but do not establish it as standard care.