Hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report

Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to affect overall survival (OS). However, the influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium from 1990 to 2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and 79.7%, respectively. Age ≥5 years, donor type, and a pre-HCT history of severe infection had a negative impact on OS and EFS, whereas pre-HCT autoimmunity had no impact. Reduced-intensity regimens were associated with lower T-cell and myeloid donor chimerism, particularly when non-busulfan-based regimens were used. Low myeloid donor chimerism was associated with lower platelet counts. Mixed chimerism was not consistently associated with post-HCT autoimmunity. Patients with class I (exon 1-2 missense and intron 5 hot spot variants) and class II variants (all others) had similar pre-HCT clinical symptom severity and no difference in OS, EFS, or platelet recovery post-HCT. In conclusion, our study showed excellent long-term OS and EFS after HCT for WAS, highlighting the importance of early HCT, before the development of severe infections. We confirmed that HCT using busulfan-based conditioning was associated with improved donor chimerism and platelet recovery. This trial was registered at www.clinicaltrials.gov as NCT02064933.

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Publication Details

Journal
Blood Advances
Published
2025-12-05
DOI
https://doi.org/10.1182/bloodadvances.2025017662
Citations
1
Primary Topic
Cellular Mechanics and Interactions
Type
article
Field-Weighted Citation Impact
1.15

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article

Hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report

Suhag H Parikh, Hilary Haines, Jacob Rozmus, Deepak Chellapandian et al.
1 citations
Blood Advances
Cellular Mechanics and Interactions
1.15
article

Hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report

Suhag H Parikh, Hilary Haines, Jacob Rozmus, Deepak Chellapandian, Evan Shereck, Kathleen E. Sullivan, Ahmad Rayes, Michael A. Pulsipher, Mark T. Vander Lugt, Holly Miller, Neena Kapoor, Jessie L. Alexander, Ashley Chopek, Jeffrey R. Andolina, Lisa Forbes Satter, Katja G. Weinacht, Jennifer M. Puck, Michael D. Keller, Sung‐Yun Pai, Alan P. Knutsen, David C. Shyr, Caridad Martinez, Alfred P. Gillio, David J. Rawlings, Luigi Daniele Notarangelo, Rebecca Marsh, Shanmuganathan Chandrakasan, Christen L. Ebens, Hannah Lust, Hesham Eissa, Christopher C. Dvorak, Andrea Bauchat, Donald B. Kohn, Blachy J. Dávila Saldaña, Jennifer Heimall, Susan E. Prockop, Morton J. Cowan, Theodore B. Moore, Kristin A. Shimano, Lolie C. Yu, Hemalatha G. Rangarajan, Malika Kapadia, Jack Bleesing, Élie Haddad, Ami J. Shah, Ruta Brazauskas, Kenneth B. DeSantes, Jeffrey J. Bednarski, Hey Chong, Alice Chan, Troy R. Torgerson, Avni Y. Joshi, Joseph H. Oved, Lauri M. Burroughs, Lisa Madden, Julie‐An Talano, Jennifer W. Leiding, Aleksandra Petrovič, Linda M. Griffith, Victor M. Aquino, Hans D. Ochs, Sravya Gethika Dammalapati
article en
1 citations

Abstract

Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to affect overall survival (OS). However, the influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium from 1990 to 2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and 79.7%, respectively. Age ≥5 years, donor type, and a pre-HCT history of severe infection had a negative impact on OS and EFS, whereas pre-HCT autoimmunity had no impact. Reduced-intensity regimens were associated with lower T-cell and myeloid donor chimerism, particularly when non-busulfan-based regimens were used. Low myeloid donor chimerism was associated with lower platelet counts. Mixed chimerism was not consistently associated with post-HCT autoimmunity. Patients with class I (exon 1-2 missense and intron 5 hot spot variants) and class II variants (all others) had similar pre-HCT clinical symptom severity and no difference in OS, EFS, or platelet recovery post-HCT. In conclusion, our study showed excellent long-term OS and EFS after HCT for WAS, highlighting the importance of early HCT, before the development of severe infections. We confirmed that HCT using busulfan-based conditioning was associated with improved donor chimerism and platelet recovery. This trial was registered at www.clinicaltrials.gov as NCT02064933.

Blood AdvancesVol. 10(5)
Intermountain Healthcare (US), Cincinnati Children's Hospital Medical Center (US), Boston Children's Hospital (US), Lurie Children's Hospital (US), Seattle Children's Hospital (US), National Institutes of Health (US), Nationwide Children's Hospital (US), Hackensack University Medical Center (US), Primary Children's Hospital (US), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), Lucile Packard Children's Hospital (US), Memorial Sloan Kettering Cancer Center (US), Children's Hospital of Philadelphia (US), Children's National (US), Children's Hospital of Los Angeles (US), University of Wisconsin–Madison (US), Johns Hopkins University (US), Emory University (US), City College of San Francisco (US), University of California, Los Angeles (US), Oregon Health & Science University (US), Duke University (US), Palo Alto University (US), University of California, San Francisco (US), Baylor College of Medicine (US), University of Washington (US), Medical College of Wisconsin (US), Washington University in St. Louis (US), University of Utah (US), University of Michigan (US), Columbia University Irving Medical Center (US), UCLA Health (US), Johns Hopkins Medicine (US), University of Minnesota System (US), Huntsman Cancer Institute (US), Centre Hospitalier Universitaire Sainte-Justine (CA), WinnMed (US), University of Rochester Medical Center (US), University of Alabama at Birmingham (US), Institute for Stem Cell Biology and Regenerative Medicine (IN), CancerCare Manitoba (CA), Fred Hutch Cancer Center (US), Cardinal Glennon Children’s Medical Center (US), Southwestern Medical Center (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 United (US), Michigan Medicine (US), Versiti Blood Center of Wisconsin (US), Children's Hospital of New Orleans (US), Dana-Farber Cancer Institute (US), Golisano Children's Hospital (US), Phoenix Children's Hospital (US), Lurie Children's Hospital (US), Methodist 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), Stanford Medicine (US), University of Wisconsin American Family Children's Hospital (US), Allen Institute (US), National Cancer Institute (US), Mayo Clinic in Florida (US), Children's Healthcare of Atlanta (US), Texas Children's Hospital (US), Hackensack Meridian Health (US), Children's Center (US), Boston Children's Museum (US), BC Children's Hospital (CA), Southwestern Medical Center (US), Robert H. Lurie Comprehensive Cancer Center of Northwestern University, University of Manitoba (CA), Saint Louis University (US), University of Cincinnati (US), Louisiana State University Health Sciences Center New Orleans (US), The University of Texas Southwestern Medical Center (US), University of Colorado Denver (US), Stanford University (US)
U.S. Department of Health and Human Services, Amgen, Eli Lilly and Company, Pfizer, Children's Hospital of Philadelphia, Memorial Sloan-Kettering Cancer Center, CSL Behring, Les Laboratories Pierre Fabre, Atara Biotherapeutics, bluebird bio, Incyte, Horizon Therapeutics, Swedish Orphan Biovitrum, Medac, Grifols, National Institutes of Health, Health Resources and Services Administration, National Heart, Lung, and Blood Institute, Office of Naval Research, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences, Daiichi Sankyo Europe, NHLBI Division of Intramural Research
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Cellular Mechanics and Interactions
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