Reduced-Intensity Haploidentical Bone Marrow Transplantation in Children with Severe Sickle Cell Disease: BMT CTN 1507

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.

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Journal
Blood Advances
Published
2026-10-28
DOI
https://doi.org/10.1182/bloodadvances.2026021576
Primary Topic
Hematopoietic Stem Cell Transplantation
Type
article
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article

Reduced-Intensity Haploidentical Bone Marrow Transplantation in Children with Severe Sickle Cell Disease: BMT CTN 1507

Robert Sheppard Nickel, Catherine M. Bollard, Michael W. Kent, Sumit Pruthi et al.
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Blood Advances
Hematopoietic Stem Cell Transplantation
article

Reduced-Intensity Haploidentical Bone Marrow Transplantation in Children with Severe Sickle Cell Disease: BMT CTN 1507

Robert Sheppard Nickel, Catherine M. Bollard, Michael W. Kent, Sumit Pruthi, Jordan Milner, Brent R. Logan, Ghada A. Abusin, Alfred P. Gillio, Elton Benjamin Greene, Jorge R. Galvez Silva, Christopher M. McKinney, Khaled Yassine, Kenneth R. Cooke, Mark C. Walters, Mary Eapen, Kris Michael Mahadeo, Michael Rutledge DeBaun, Adetola A. Kassim, Lori C. Jordan, Lakshmanan Krishnamurti, Hemalatha G. Rangarajan, Adam M. Mendizabal, Jodi L. Skiles, Eric Leifer, Robert Alan Brodsky, Gregory Anthony Yanik, Mary M. Horowitz, Nicole Ritzau, Richard Julian Jones, Madoc Smith
article en

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.

Blood Advances
Nationwide Children's Hospital (US), Children's National (US), Johns Hopkins University (US), University of California, San Francisco (US), Baylor College of Medicine (US), Vanderbilt University (US), Medical College of Wisconsin (US), University of Michigan (US), Riley Hospital for Children (US), Yale University (US), University of Florida (US), National Heart, Lung, and Blood Institute (US), Michigan United (US), Emmes (United States) (US), Duke Medical Center (US), Levine Children's Hospital (US), UCSF Benioff Children's Hospital (US), Miami Children's Hospital (US), Texas Children's Hospital (US), Hackensack Meridian Health (US), C. S. Mott Children's Hospital (US), Sidney Kimmel Comprehensive Cancer Center (US), University of Colorado Anschutz Medical Campus (US), Vanderbilt University Medical Center (US)
National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases
Good health and well-being
Openalex Percentile: Top 12%
Hematopoietic Stem Cell Transplantation
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