Outcomes following matched sibling donor transplantation for severe combined immunodeficiency: a report from the PIDTC

The Primary Immune Deficiency Treatment Consortium performed a retrospective analysis of 133 patients with severe combined immunodeficiency (SCID) receiving matched sibling donor (MSD) hematopoietic cell transplantation (HCT) between 1980 and 2023 at 30 North American institutions. In this largest cohort of MSD outcomes in patients with SCID to date, we examined the impact of conditioning regimen and graft-versus-host disease (GVHD) prophylaxis on survival and immune recovery. Outcomes after MSD HCT for SCID were excellent. Patients without an active infection or failure to thrive (FTT) at the time of HCT had 5-year overall survival superior to those with infection or FTT. Acute and chronic GVHD outcomes were independent of GVHD prophylaxis, conditioning regimen, SCID type, or presence of maternal engraftment. Patients without active infection at the time of HCT had superior chronic GVHD-free event-free survival vs those with infection. T-cell reconstitution at 6 months was less likely achieved with use of GVHD prophylaxis or serotherapy, and in patients with leaky SCID or Omenn syndrome. At 6 months, 1 year, and 2-5 years, T-cell reconstitution was less likely with ADA, DCLRE1C, or RAG genotype. B-cell reconstitution at 1 year and 2-5 years was negatively affected by development of grade 2 to 4 or 3 to 4 acute GVHD. Conditioning did not affect T- or B-cell reconstitution. Our data suggest omitting conditioning and GVHD prophylaxis for patients with typical SCID did not negatively affect 5-year outcomes after MSD HCT, but the data are insufficient to recommend this approach for best long-term outcomes. This trial was registered at www.clinicaltrials.gov as #NCT01186913 and #NCT01346150.

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Journal
Blood Advances
Published
2025-11-25
DOI
https://doi.org/10.1182/bloodadvances.2025016812
Primary Topic
Immunodeficiency and Autoimmune Disorders
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article
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article

Outcomes following matched sibling donor transplantation for severe combined immunodeficiency: a report from the PIDTC

Nancy Bunin, Hilary Haines, Deepak Chellapandian, Roberta Parrott et al.
Blood Advances
Immunodeficiency and Autoimmune Disorders
article

Outcomes following matched sibling donor transplantation for severe combined immunodeficiency: a report from the PIDTC

Nancy Bunin, Hilary Haines, Deepak Chellapandian, Roberta Parrott, Evan Shereck, Ahmad Rayes, Michael A. Pulsipher, Mark T. Vander Lugt, Holly Miller, Neena Kapoor, Monica S. Thakar, Geoff D.E. Cuvelier, Jessie L. Alexander, Jennifer M. Puck, Michael D. Keller, Sung‐Yun Pai, Alan P. Knutsen, Brent R. Logan, Caridad Martinez, Alfred P. Gillio, Luigi Daniele Notarangelo, Rebecca Marsh, Shanmuganathan Chandrakasan, Christine M. Seroogy, Christen L. Ebens, Christopher C. Dvorak, Donald B. Kohn, Blachy J. Dávila Saldaña, Jennifer Heimall, Susan E. Prockop, Morton J. Cowan, Karin Chen, Paibel Aguayo‐Hiraldo, Malika Kapadia, Hesham Eissa, Élie Haddad, Ami J. Shah, Jeffrey J. Bednarski, Troy R. Torgerson, Sonali Chaudhury, Talal Mousallem, Sharat Chandra, Morna J. Dorsey, Joseph H. Oved, Jasmeen Dara, Lauri M. Burroughs, Julie‐An Talano, Jennifer W. Leiding, Rebecca H. Buckley, Xuerong Liu, Linda M. Griffith, Richard J. O’Reilly, Victor M. Aquino
article en

Abstract

The Primary Immune Deficiency Treatment Consortium performed a retrospective analysis of 133 patients with severe combined immunodeficiency (SCID) receiving matched sibling donor (MSD) hematopoietic cell transplantation (HCT) between 1980 and 2023 at 30 North American institutions. In this largest cohort of MSD outcomes in patients with SCID to date, we examined the impact of conditioning regimen and graft-versus-host disease (GVHD) prophylaxis on survival and immune recovery. Outcomes after MSD HCT for SCID were excellent. Patients without an active infection or failure to thrive (FTT) at the time of HCT had 5-year overall survival superior to those with infection or FTT. Acute and chronic GVHD outcomes were independent of GVHD prophylaxis, conditioning regimen, SCID type, or presence of maternal engraftment. Patients without active infection at the time of HCT had superior chronic GVHD-free event-free survival vs those with infection. T-cell reconstitution at 6 months was less likely achieved with use of GVHD prophylaxis or serotherapy, and in patients with leaky SCID or Omenn syndrome. At 6 months, 1 year, and 2-5 years, T-cell reconstitution was less likely with ADA, DCLRE1C, or RAG genotype. B-cell reconstitution at 1 year and 2-5 years was negatively affected by development of grade 2 to 4 or 3 to 4 acute GVHD. Conditioning did not affect T- or B-cell reconstitution. Our data suggest omitting conditioning and GVHD prophylaxis for patients with typical SCID did not negatively affect 5-year outcomes after MSD HCT, but the data are insufficient to recommend this approach for best long-term outcomes. This trial was registered at www.clinicaltrials.gov as #NCT01186913 and #NCT01346150.

Blood AdvancesVol. 10(3)
Children's Hospital of Wisconsin (US), Cincinnati Children's Hospital Medical Center (US), National Institutes of Health (US), Hackensack University Medical Center (US), Primary Children's Hospital (US), BJC HealthCare (US), Memorial Sloan Kettering Cancer Center (US), Children's Hospital of Philadelphia (US), Children's National (US), Children's Hospital of Los Angeles (US), Johns Hopkins University (US), University of California, Los Angeles (US), Oregon Health & Science University (US), Duke University (US), Palo Alto University (US), Baylor College of Medicine (US), Medical College of Wisconsin (US), Washington University in St. Louis (US), University of Michigan (US), Johns Hopkins Medicine (US), Huntsman Cancer Institute (US), Alberta Children's Hospital (CA), Centre Hospitalier Universitaire Sainte-Justine (CA), University of Alabama at Birmingham (US), Fred Hutch Cancer Center (US), Cardinal Glennon Children’s Medical Center (US), Children's Hospital Colorado (US), Johns Hopkins All Children's Hospital (US), Allen Institute for Immunology (US), Seattle Children's Hospital (US), Center for Cancer and Blood Disorders (US), Michigan Medicine (US), Dana-Farber Cancer Institute (US), Lurie Children's Hospital (US), Children's Hospital of Pittsburgh (US), National Institute of Allergy and Infectious Diseases (US), University of Minnesota Medical Center (US), UCSF Benioff Children's Hospital (US), University of Wisconsin American Family Children's Hospital (US), Allen Institute (US), National Cancer Institute (US), Immune Regulation (United Kingdom) (GB), Office of Extramural Research (US), Children's Healthcare of Atlanta (US), Texas Children's Hospital (US), Hackensack Meridian Health (US), National Institutes of Health Clinical Center (US), Robert H. Lurie Comprehensive Cancer Center of Northwestern University, The University of Texas Southwestern Medical Center (US), University of Colorado Denver (US), Stanford University (US)
U.S. Department of Health and Human Services, Aflac, Amgen, Pfizer, Children's Hospital of Philadelphia, Emory University, Memorial Sloan-Kettering Cancer Center, Northwestern University, Texas Children's Hospital, Cincinnati Children's Hospital Medical Center, Children's Hospital Colorado, University of Minnesota, California Institute of Regenerative Medicine, University of Washington, Johns Hopkins University, University of Cincinnati, Seattle Children's Research Institute, Saint Louis University, Children’s Hospital of Wisconsin Research Institute, Children's Healthcare of Atlanta, Les Laboratories Pierre Fabre, Atara Biotherapeutics, bluebird bio, Rare Diseases Clinical Research Network, Children's National Hospital, National Institutes of Health, Health Resources and Services Administration, Feinberg School of Medicine, Office of Naval Research, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences, Children's Hospital of Pittsburgh, NHLBI Division of Intramural Research
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