Evidence map›Paper›PMID 25898053›Full record

Trial reportJAMA2015

Outcomes following gene therapy in patients with severe Wiskott-Aldrich syndrome.

Salima Hacein-Bey Abina, H Bobby Gaspar, Johanna Blondeau, Laure Caccavelli, Sabine Charrier, Karen Buckland, Capucine Picard, Emmanuelle Six, Nourredine Himoudi, Kimberly Gilmour and 23 more

Registry-linked trialAbstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in JAMA, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03538899 (Phase I/II Safety and Efficacy Study of Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency), which is not on this map. Cited by 187 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
187citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03538899 phase1 / phase2recruitingnot on this mapstarted 2018, after this paper: background citation

Phase I/II Safety and Efficacy Study of Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency (ART-SCID) in Newly Diagnosed Patients Using Self-Inactivating Lentiviral Vector (AProArt) to Transduce Autologous CD34 Hematopoietic Cells

TypeinterventionalSponsorUniversity of California, San FranciscoRan2018 to 2038Enrolled24ConditionsSevere Combined ImmunodeficiencyArmsAProArt-CD34, CliniMACS® CD34 Reagent System cell sorter device, Busulfan
3 · Its place in the literature

Who cites it

187 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Review
  7. Review
  8. Review
  9. Review
  10. Ex Vivo Gene and Cell Therapy in Hematopoietic Stem Cells.International journal of molecular sciences · 2025
    Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. It's all about location: Targeting the right spot for Wiskott-Aldrich syndrome.Molecular therapy. Methods & clinical development · 2024
    Article
  20. Article

127 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors.

Salima Hacein-Bey AbinaBiotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France2Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, Paris, France3Unité de.
H Bobby GasparSection of Molecular and Cellular Immunology, University College London Institute of Child Health, London, England6Department of Clinical Immunology, Hospital National Health Service Foundation Trust, London, England.
Johanna BlondeauBiotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France2Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, Paris, France.
Laure CaccavelliBiotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France2Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, Paris, France.
Sabine CharrierINSERM U951, Unité Mixte de Recherche S951, Molecular Immunology and Innovative Biotherapies, University of Evry, Evry, France8Genethon, Evry, France.
Karen BucklandSection of Molecular and Cellular Immunology, University College London Institute of Child Health, London, England6Department of Clinical Immunology, Hospital National Health Service Foundation Trust, London, England.
Capucine PicardCentre d'Étude des Déficits Immunitaires, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France10Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France11Immunology and Pediatric Hematology Departmen.
Emmanuelle SixParis Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France12INSERM Unité Mixte de Recherche 1163, Laboratory of Human Lymphohematopoiesis, Paris, France.
Nourredine HimoudiSection of Molecular and Cellular Immunology, University College London Institute of Child Health, London, England6Department of Clinical Immunology, Hospital National Health Service Foundation Trust, London, England.
Kimberly GilmourSection of Molecular and Cellular Immunology, University College London Institute of Child Health, London, England6Department of Clinical Immunology, Hospital National Health Service Foundation Trust, London, England.
Anne-Marie McNicolSection of Molecular and Cellular Immunology, University College London Institute of Child Health, London, England6Department of Clinical Immunology, Hospital National Health Service Foundation Trust, London, England.
Havinder HaraSection of Molecular and Cellular Immunology, University College London Institute of Child Health, London, England6Department of Clinical Immunology, Hospital National Health Service Foundation Trust, London, England.
Jinhua Xu-BayfordDepartment of Clinical Immunology, Hospital National Health Service Foundation Trust, London, England.
Christine RivatSection of Molecular and Cellular Immunology, University College London Institute of Child Health, London, England6Department of Clinical Immunology, Hospital National Health Service Foundation Trust, London, England.
Fabien TouzotBiotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France2Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, Paris, France10Paris D.
Fulvio MavilioGenethon, Evry, France.
Annick LimGroupe Immunoscope, Immunology Department, Institut Pasteur, Paris, France.
Jean-Marc TreluyerClinical Research Center Necker-Enfants Malades and Cochin Hospital Assistance Publique-Hôpitaux de Paris, Paris Descartes University.
Sébastien HéritierParis Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France11Immunology and Pediatric Hematology Department, Assistance Publique-Hôpitaux de Paris, Paris, France.
Francois LefrèreBiotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Jeremy MagalonBiotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France2Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, Paris, France.
Isabelle Pengue-KoyiBiotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France2Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, Paris, France10Paris D.
Géraldine HonnetGenethon, Evry, France.
Stéphane BlancheParis Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France11Immunology and Pediatric Hematology Department, Assistance Publique-Hôpitaux de Paris, Paris, France.
Eric A ShermanDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia.
Frances MaleDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia.
Charles BerryDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia.
Nirav MalaniDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia.
Frederic D BushmanDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia.
Alain FischerParis Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France11Immunology and Pediatric Hematology Department, Assistance Publique-Hôpitaux de Paris, Paris, France12INSERM Unité Mixte de Recherche 1163, Laboratory of Human Lymphohematop.
Adrian J ThrasherSection of Molecular and Cellular Immunology, University College London Institute of Child Health, London, England6Department of Clinical Immunology, Hospital National Health Service Foundation Trust, London, England.
Anne GalyINSERM U951, Unité Mixte de Recherche S951, Molecular Immunology and Innovative Biotherapies, University of Evry, Evry, France8Genethon, Evry, France.
Marina CavazzanaBiotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France2Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, Paris, France10Paris D.

Funding

Massively Parallel Analysis of Integration in Therapeutic Gene TransferR01AI082020 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D · 2009 to 2018
$3.5M
NIAID NIH HHS R01 AI082020Wellcome Trust
6 · The paper itself

Abstract

importanceWiskott-Aldrich syndrome is a rare primary immunodeficiency associated with severe microthrombocytopenia. Partially HLA antigen-matched allogeneic hematopoietic stem cell (HSC) transplantation is often curative but is associated with significant comorbidity.

objectiveTo assess the outcomes and safety of autologous HSC gene therapy in Wiskott-Aldrich syndrome. DESIGN, SETTING, AND

participantsGene-corrected autologous HSCs were infused in 7 consecutive patients with severe Wiskott-Aldrich syndrome lacking HLA antigen-matched related or unrelated HSC donors (age range, 0.8-15.5 years; mean, 7 years) following myeloablative conditioning. Patients were enrolled in France and England and treated between December 2010 and January 2014. Follow-up of patients in this intermediate analysis ranged from 9 to 42 months.

interventionA single infusion of gene-modified CD34+ cells with an advanced lentiviral vector. MAIN OUTCOMES AND MEASURES: Primary outcomes were improvement at 24 months in eczema, frequency and severity of infections, bleeding tendency, and autoimmunity and reduction in disease-related days of hospitalization. Secondary outcomes were improvement in immunological and hematological characteristics and evidence of safety through vector integration analysis.

resultsSix of the 7 patients were alive at the time of last follow-up (mean and median follow-up, 28 months and 27 months, respectively) and showed sustained clinical benefit. One patient died 7 months after treatment of preexisting drug-resistant herpes virus infection. Eczema and susceptibility to infections resolved in all 6 patients. Autoimmunity improved in 5 of 5 patients. No severe bleeding episodes were recorded after treatment, and at last follow-up, all 6 surviving patients were free of blood product support and thrombopoietic agonists. Hospitalization days were reduced from a median of 25 days during the 2 years before treatment to a median of 0 days during the 2 years after treatment. All 6 surviving patients exhibited high-level, stable engraftment of functionally corrected lymphoid cells. The degree of myeloid cell engraftment and of platelet reconstitution correlated with the dose of gene-corrected cells administered. No evidence of vector-related toxicity was observed clinically or by molecular analysis. CONCLUSIONS AND RELEVANCE: This study demonstrated the feasibility of the use of gene therapy in patients with Wiskott-Aldrich syndrome. Controlled trials with larger numbers of patients are necessary to assess long-term outcomes and safety.

Indexed as

Genetic TherapyGenetic VectorsHematopoietic Stem Cell TransplantationLentivirusAdolescentChildChild, PreschoolFeasibility StudiesGene ExpressionHumansInfantInfant, NewbornMaleSeverity of Illness IndexWiskott-Aldrich SyndromeWiskott-Aldrich Syndrome Protein FamilyWiskott-Aldrich Syndrome Protein Family

Identifiers

PMID25898053
PMCPMC4942841

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.