Reduced-Intensity Haploidentical Bone Marrow Transplantation in Children with Severe Sickle Cell Disease: BMT CTN 1507
In brief
Haploidentical transplant leaves 79% of children event-free at two years
In this phase 2 trial, 39 children with severe sickle cell disease received a transplant from a half-matched donor; 79% were alive and disease-free at two years, and overall survival was 95%. No new or worsening brain infarcts appeared in 22 children with follow-up MRI, but graft failure and graft-versus-host disease reduced event-free survival, and the single-arm study cannot establish comparative benefit.
- Journal
- Blood advances (Q1)
- Published
- 28 October 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Mark C Walters, Adetola A Kassim, Mary Eapen, Lori C Jordan, Sumit Pruthi, Elton B Greene, et al.
- PMID
- 42950248
- DOI
- 10.1182/bloodadvances.2026021576
Why clinicians should know about it
- Picked for Hematology (paper of the day, 31 October 2026): Reduced‑intensity haploidentical BMT for severe sickle cell disease
Abstract
This is a multi-center, single-arm, phase-II, trial (NCT03263559) of haploidentical bone marrow transplant (BMT) for children with severe sickle cell disease (SCD). Eligible participants were children 5.00 - 14.99 years of age with stroke (silent or overt), abnormal transcranial Doppler cerebral arterial velocity > 200 cm/sec with intracranial vasculopathy, severe acute chest syndrome (ACS) or recurrent vaso-occlusive pain. The primary outcome was 2-year event-free survival (EFS; alive and disease-free). The transplant regimen included hydroxyurea 30mg/kg/day (Day-60 to Day-10), followed by thymoglobulin, thiotepa, fludarabine, cyclophosphamide, and total body irradiation (200 cGy). Graft-versus-host disease (GVHD) prophylaxis included post-transplant cyclophosphamide (PTCy), sirolimus and mycophenolate mofetil. Forty-one participants were enrolled from 18 sites and 95% (39/41) proceeded to BMT. The median age at enrollment was 12.5 years; 98% (38/39) had hemoglobin SS disease, and 82.1% (32/39) had donors mismatched at 4 HLA-loci. The most common indication for BMT was a qualifying neurological event in 69% (27/39), including 15 with overt stroke. Nine participants had recurrent vaso-occlusive pain and 5, severe ACS. The 2-year EFS and overall survival were 79.3% (95% CI: 62.8%, 89.1) and 94.5% (95% CI: 79.7%, 98.6%), respectively. FEV1% predicted increased from 79.5 to 95.7 at 2 years (p=0.014), and eGFR declined from 174 to 127 mL/min/1.73m2 (p<0.001), indicating resolved hyperfiltration. No new or progressive cerebral infacts were detected by serial brain MRI per central adjudication (n=22). While graft failure and GVHD negatively impacted EFS, reduced-intensity haploidentical BMT with PTCy is a promising therapy for children who lack a matched sibling donor.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.