Reduced-Intensity Haploidentical Bone Marrow Transplantation in Children with Severe Sickle Cell Disease: BMT CTN 1507
Year: 2026
Type: article
Study design: Clinical Trial
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.
Source: Blood Advances
Authors: Mark C. Walters, Adetola A. Kassim, Mary Eapen, Lori C Jordan, Sumit Pruthi, Elton B Greene, Madoc Smith, Jordan Milner, Robert S Nickel, Catherine M. Bollard, Alfred P Gillio, Khaled Yassine, Jodi Skiles, Christopher M. McKinney, Hemalatha G. Rangarajan, Ghada Abusin, Gregory A Yanik, Jorge R Galvez Silva, Michael Kent, Nicole RItzau, Adam M Mendizabal, Kris Michael Michael Mahadeo, Lakshmanan Krishnamurti, Kenneth R Cooke, Eric Leifer, Brent R. Logan, Mary M Horowitz, Richard J. Jones, Robert A. Brodsky, Michael R DeBaun
Institutions: University of California, San Francisco, UCSF Benioff Children's Hospital, Vanderbilt University Medical Center, Medical College of Wisconsin, Vanderbilt University, Emmes (United States), University of Florida, Children's National, Hackensack Meridian Health, Baylor College of Medicine, Texas Children's Hospital, Riley Hospital for Children, University of Colorado Anschutz, Nationwide Children's Hospital, University of Michigan, C. S. Mott Children's Hospital, Miami Children's Hospital, Levine Children's Hospital, Duke Medical Center, Yale University, Johns Hopkins University, National Heart, Lung, and Blood Institute, Sidney Kimmel Comprehensive Cancer Center
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
Awards: Sickle Cell Disease Cure Initiative (SCDC), Blood & Marrow Transplant Clinical Trials Network Data Coordinating Center, A Data Resource for Blood and Marrow Transplants and Adoptive Cellular Therapy Research, Blood and Marrow Transplant Clinical Trials Network DCC- The Medical College of Wisconsin, Inc.
OpenAlex ID: W7224104545