Evidence map›Paper›PMID 41092330›Full record

Observational studyThe New England journal of medicine2025

Long-Term Safety and Efficacy of Gene Therapy for Adenosine Deaminase Deficiency.

Claire Booth, Katelyn Masiuk, Konstantinos Vazouras, Augustine Fernandes, Jinhua Xu-Bayford, Beatriz Campo Fernandez, Sohini Roy, Beatrice Curio-Penny, Jordyn Arnold, Dayna Terrazas and 21 more

Registry-linked trialAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The New England journal of medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04049084 (An Observational Long-term Follow-up Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–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.

NCT04049084 enrolling by invitationnot on this map

An Observational Long-term Follow-up Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID)

Typeobservational_patient_registrySponsorUniversity of California, Los AngelesRan2019 to 2040Enrolled70ConditionsAdenosine Deaminase Deficiency, Severe Combined Immunodeficiency (SCID)Armsautologous ex vivo gene therapy products based on the EFS LV encoding for the human adenosine deaminase (ADA) gene (EFS-ADA LV)
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. International journal of biological sciences · 2026
    Review
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors.

Claire BoothUniversity College London Great Ormond Street Institute of Child Health, London.
Katelyn MasiukDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles.
Konstantinos VazourasUniversity College London Great Ormond Street Institute of Child Health, London.
Augustine FernandesDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles.
Jinhua Xu-BayfordDepartment of Paediatric Immunology and Gene Therapy, Great Ormond Street Hospital for Sick Children NHS Foundation Trust, London.
Beatriz Campo FernandezDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles.
Sohini RoyDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles.
Beatrice Curio-PennyDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles.
Jordyn ArnoldDepartment of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles.
Dayna TerrazasDepartment of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles.
Jack ReidDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles.ORCID 0009-0005-8080-8302
Kimberly C GilmourDepartment of Immunology, National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, London.
Stuart AdamsDepartment of Haematology, Great Ormond Street Children's Hospital, London.ORCID 0000-0002-2650-2848
Elena Alvarez MediavillaUniversity College London Great Ormond Street Institute of Child Health, London.
Lana MhaldienDepartment of Immunology, National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, London.
Grainne O'TooleDepartment of Paediatric Immunology and Gene Therapy, Great Ormond Street Hospital for Sick Children NHS Foundation Trust, London.
Rima AhmedDepartment of Paediatric Immunology and Gene Therapy, Great Ormond Street Hospital for Sick Children NHS Foundation Trust, London.
Elizabeth GarabedianNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
Harry MalechSection of Genetic Immunotherapy, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Suk See De RavinSection of Genetic Immunotherapy, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Theodore B MooreDepartment of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles.
Satiro De OliveiraDepartment of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles.
Danilo PellinGene Therapy Program, Dana-Farber-Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston.
Tsai-Yu LinDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis.ORCID 0000-0002-8076-1584
Thao Thi DangDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis.
Kenneth CornettaDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis.
Michael S HershfieldDuke University Medical Center, Durham, North Carolina.
Havinder HaraUniversity College London Great Ormond Street Institute of Child Health, London.
Adrian J ThrasherUniversity College London Great Ormond Street Institute of Child Health, London.
H Bobby GasparUniversity College London Great Ormond Street Institute of Child Health, London.
Donald B KohnDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles.

Funding

Data Resource for Analyzing Blood &Marrow TransplantsU24CA076518 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI Amy M Moskop, Bronwen Shaw · 1998 to 2026
$105.2M
PB vs. BMU01HL069294 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI HOROWITZ, MARY MARESCA · 2001 to 2010
$63.3M
Rare Diseases Data Management and Coordinating CenterU01TR001263 · NCATS · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2014 to 2018
$28.1M
Training of Clinical Investigators in Primary Immune DeficienciesU54AI082973 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PAI, SUNG-YUN · 2009 to 2023
$23.3M
Transduction of Human Stem and Progenitor CellsP01HL073104 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOHN, DONALD B · 2003 to 2013
$18.3M
Data Management and Coordinating Center (DMCC)U54NS064808 · NINDS · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2009 to 2013
$16.5M
Primary Immune Deficiency Treatment Consortium (PIDTC): A resource to drive scientific and clinical advances related to the treatment of inborn errors of immunityR24AI184316 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Christopher Craig Dvorak, Elie Haddad · 2024 to 2026
$5.3M
EFS-ADA Lentiviral Vector Transduction of Bone Marrow CD34+ Cells for ADA-SCIDU01AI100801 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOHN, DONALD B · 2012 to 2016
$3.2M
PURPOSE OF THE NGVB CONTRACT IS TO CONTINUE SUPPORTING GENE THERAPY RESEARCH.75N92019D00018 · OD · INDIANA UNIVERSITY INDIANAPOLIS · 2019 to 2023
$1.7M
GENE THERAPY FOR IMMUNE DEFICIENCIESZ01AI000645 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI DE RAVIN, SUK · 1992 to 2008
$873k
Blood and Marrow Transplant Clinical Trials NetworkU10HL069254 · NHLBI · UNIVERSITY OF UTAH · PI PULSIPHER, MICHAEL A · 2011 to 2016
$839k
California Institute for Regenerative Medicine CLIN2-09339Doris Duke Charitable Foundation 20000654Intramural NIH HHS Z01 AI000645NCATS NIH HHS U01 TR001263NCI NIH HHS U24 CA076518NHLBI NIH HHS 75N92019D00018NHLBI NIH HHS P01 HL073104NHLBI NIH HHS U01 HL069294NHLBI NIH HHS U10 HL069254NIAID NIH HHS R24 AI184316NIAID NIH HHS U01 AI100801NIAID NIH HHS U54 AI082973NINDS NIH HHS U54 NS064808
6 · The paper itself

Abstract

backgroundSevere combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency (ADA-SCID) is a life-threatening inborn error of immunity for which lentiviral gene therapy has been investigated in clinical trials.

methodsBetween 2012 and 2019, we treated patients who had ADA-SCID with busulfan nonmyeloablative conditioning followed by transplantation with autologous CD34+ hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding human

resultsWe treated 62 patients with ADA-SCID in the United States (33 patients) and the United Kingdom (29 patients). Overall survival was 100%, and event-free survival was 95% (59 of 62 patients). All 59 patients who had successful gene-marked engraftment at 6 months have continued not to receive enzyme-replacement therapy and have had stable gene marking, ADA enzyme activity, metabolic detoxification, and immune reconstitution through the last follow-up; 58 of these patients (98%) discontinued IgG replacement therapy and have evidence of a robust response to vaccinations. None of the patients had a leukoproliferative event or clonal expansion.

conclusionsThese long-term findings in a large patient cohort show the sustained clinical efficacy and safety of autologous CD34+ hematopoietic stem-cell lentiviral gene therapy for ADA-SCID, indicating that it is a curative treatment. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT04049084.).

Indexed as

Adenosine DeaminaseAgammaglobulinemiaGenetic TherapyHematopoietic Stem Cell TransplantationSevere Combined ImmunodeficiencyAdolescentChildChild, PreschoolFemaleFollow-Up StudiesGenetic VectorsHumansImmunoglobulin GInfantLentivirusMaleADA protein, humanAdenosine DeaminaseImmunoglobulin G

Identifiers

PMID41092330
PMCPMC13682835

What OpenQuestion holds

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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.