ArticleJournal of clinical immunology2015
Outcomes in two Japanese adenosine deaminase-deficiency patients treated by stem cell gene therapy with no cytoreductive conditioning.
Article in Journal of clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders.Nature communications · 2022Pooled it
- Cytoreductive conditioning intensity predicts clonal diversity in ADA-SCID retroviral gene therapy patients.Blood · 2017Trial
- Safety and efficacy of elapegademase in patients with adenosine deaminase deficiency: A multicenter, open-label, single-arm, phase 3, and postmarketing clinical study.Immunity, inflammation and disease · 2023Review
- Therapeutics in paediatric genetic diseases: Current and future landscape.Singapore medical journal · 2023Review
- Management of Inborn Errors of Immunity in the Genomic Era.Turkish archives of pediatrics · 2022Article
- Review of Treatment for Adenosine Deaminase Deficiency (ADA) Severe Combined Immunodeficiency (SCID).Therapeutics and clinical risk management · 2022Review
- Nonconditioned ADA-SCID gene therapy reveals ADA requirement in the hematopoietic system and clonal dominance of vector-marked clones.Molecular therapy. Methods & clinical development · 2021Article
- Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders.Open life sciences · 2021Review
- Gene therapy and genome editing for primary immunodeficiency diseases.Genes & diseases · 2020Review
- Application of Flow Cytometry in Primary Immunodeficiencies: Experience From India.Frontiers in immunology · 2019Review
- Gene therapy in rare diseases: the benefits and challenges of developing a patient-centric registry for Strimvelis in ADA-SCID.Orphanet journal of rare diseases · 2018Article
- Single Cell-Based Vector Tracing in Patients with ADA-SCID Treated with Stem Cell Gene Therapy.Molecular therapy. Methods & clinical development · 2017Article
- Gene therapy for primary immune deficiencies: a Canadian perspective.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2017Review
- Current status of ex vivo gene therapy for hematological disorders: a review of clinical trials in Japan around the world.International journal of hematology · 2016Review
- Clinical development of gene therapy: results and lessons from recent successes.Molecular therapy. Methods & clinical development · 2016Review
Corrections and comments
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Authors and funding
23 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveWe here describe treatment outcomes in two adenosine deaminase (ADA)-deficiency patients (pt) who received stem cell gene therapy (SCGT) with no cytoreductive conditioning. As this protocol has features distinct from those of other clinical trials, its results provide insights into SCGT for ADA deficiency. PATIENTS AND
methodsPt 1 was treated at age 4.7 years, whereas pt 2, who had previously received T-cell gene therapy, was treated at age 13 years. Bone marrow CD34(+) cells were harvested after enzyme replacement therapy (ERT) was withdrawn; following transduction of ADA cDNA by the γ-retroviral vector GCsapM-ADA, they were administered intravenously. No cytoreductive conditioning, at present considered critical for therapeutic benefit, was given before cell infusion. Hematological/immunological reconstitution kinetics, levels of systemic detoxification, gene-marking levels, and proviral insertion sites in hematopoietic cells were assessed.
resultsTreatment was well tolerated, and no serious adverse events were observed. Engraftment of gene-modified repopulating cells was evidenced by the appearance and maintenance of peripheral lymphocytes expressing functional ADA. Systemic detoxification was moderately achieved, allowing temporary discontinuation of ERT for 6 and 10 years in pt 1 and pt 2, respectively. Recovery of immunity remained partial, with lymphocyte counts in pts 1 and 2, peaked at 408/mm(3) and 1248/mm(3), approximately 2 and 5 years after SCGT. Vector integration site analyses confirmed that hematopoiesis was reconstituted with a limited number of clones, some of which were shown to have myelo-lymphoid potential.
conclusionsOutcomes in SCGT for ADA-SCID are described in the context of a unique protocol, which used neither ERT nor cytoreductive conditioning. Although proven safe, immune reconstitution was partial and temporary. Our results reiterate the importance of cytoreductive conditioning to ensure greater benefits from SCGT.
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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.