Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients.

Autor: Hashem H; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Bone Marrow Transplant Unit, King Hussein Cancer Center (KHCC), P.O Box 1269, Amman, 11941, Jordan. hh.08847@khcc.jo., Bucciol G; Department of Pediatrics, ERN RITA Core Center, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.; Department of Microbiology, Immunology and Transplantation, Laboratory for Inborn Errors of Immunity, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium., Ozen S; Department of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey.; Hacettepe University Vasculitis Research Center, Ankara, Turkey., Unal S; Department of Pediatric Hematology, Research Center for Fanconi Anemia and Other Inherited Bone Marrow Failure Syndromes, Hacettepe University, Ankara, Turkey., Bozkaya IO; Division of Pediatric Hematology and Oncology, Bone Marrow Transplant Unit, University of Health Sciences, Ankara City Hospital, Ankara, Turkey., Akarsu N; Department of Medical Genetics, Hacettepe University, Sihhiye, 06100, Ankara, Turkey., Taskinen M; Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Helsinki University Hospital, Helsinki, Finland., Koskenvuo M; Pediatric Hematology, Oncology and Stem Cell Transplantation, Children and Adolescents, Helsinki University Hospital, Helsinki, Finland., Saarela J; Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.; Centre for Molecular Medicine Norway, University of Oslo, Oslo, Norway., Dimitrova D; Experimental Transplantation and Immunotherapy Branch, National Cancer Institute of the National Institutes of Health, Bethesda, MD, USA., Hickstein DD; Immune Deficiency Cellular Therapy Program, CCR, NCI, MD, Bethesda, USA., Hsu AP; Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Holland SM; Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Krance R; Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA., Sasa G; Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA., Kumar AR; Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; University of Cincinnati College of Medicine, Cincinnati, OH, USA., Müller I; Division of Pediatric Stem Cell Transplantation and Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., de Sousa MA; Division of Pediatric Stem Cell Transplantation and Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Delafontaine S; Department of Pediatrics, ERN RITA Core Center, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.; Department of Microbiology, Immunology and Transplantation, Laboratory for Inborn Errors of Immunity, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium., Moens L; Department of Microbiology, Immunology and Transplantation, Laboratory for Inborn Errors of Immunity, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium., Babor F; Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany., Barzaghi F; San Raffaele Telethon Institute for Gene Therapy (TIGET), Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute Milan, Milan, Italy., Cicalese MP; Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy., Bredius R; Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, Netherlands., van Montfrans J; Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, Netherlands., Baretta V; Pediatric Hematology Oncology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy., Cesaro S; Pediatric Hematology Oncology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy., Stepensky P; Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah University Medical Center, Jerusalem, Israel., Benedicte N; Pediatric Immunology, Hematology and Rheumatology Unit, Hôpital Necker-Enfants Malades, APHP, Paris, France., Moshous D; Pediatric Immunology, Hematology and Rheumatology Unit, Hôpital Necker-Enfants Malades, APHP, Paris, France., Le Guenno G; Department of Internal Medicine, University Hospital Estaing, CHU Clermont-Ferrand, Clermont-Ferrand, France., Boutboul D; Clinical Immunology Department, Hospital Saint Louis, Université de Paris, Paris, France., Dalal J; Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, OH, USA., Brooks JP; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Dokmeci E; Department of Pediatrics, University of New Mexico, Albuquerque, NM, USA., Dara J; Department of Pediatrics, Division of Allergy, Immunology, Blood and Marrow Transplantation, University of California San Francisco, San Francisco, CA, USA., Lucas CL; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Hambleton S; Newcastle University Translational and Clinical Research Institute and Great North Children's Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, , Newcastle Upon Tyne, UK., Wilson K; Department of Hematology, University Hospital of Wales, Cardiff, UK., Jolles S; Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK., Koc Y; Stem Cell Transplant Unit, Medicana International, Istanbul, Turkey., Güngör T; Division of Hematology/Oncology/Immunology, Gene Therapy, and Stem Cell Transplantation, University Children's Hospital Zurich - Eleonore Foundation & Children's Research Center (CRC), Steinwiesstrasse 75, CH-8032, Zurich, Switzerland., Schnider C; Pediatric Immuno-Rheumatology of Western Switzerland, Department Women-Mother-Child, Lausanne University Hospital, Lausanne, Switzerland., Candotti F; Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Steinmann S; Department of Pediatrics, University Medical Center Ulm, Ulm, Germany., Schulz A; Department of Pediatrics, University Medical Center Ulm, Ulm, Germany., Chambers C; Vanderbilt University Medical Center, Nashville, TN, USA., Hershfield M; Department of Medicine and Biochemistry, Duke University Medical Center, Durham, NC, USA., Ombrello A; Metabolic, Cardiovascular, and Inflammatory Disease Genomics Branch, National Human Genome Research Institute (NHGRI), Bethesda, MD, USA., Kanakry JA; Experimental Transplantation and Immunotherapy Branch, National Cancer Institute of the National Institutes of Health, Bethesda, MD, USA., Meyts I; Department of Pediatrics, ERN RITA Core Center, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. isabelle.meyts@uzleuven.be.; Department of Microbiology, Immunology and Transplantation, Laboratory for Inborn Errors of Immunity, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. isabelle.meyts@uzleuven.be.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2021 Oct; Vol. 41 (7), pp. 1633-1647. Date of Electronic Publication: 2021 Jul 29.
DOI: 10.1007/s10875-021-01098-0
Abstrakt: Purpose: Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2.
Methods: We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS).
Results: Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2-28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5-16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT.
Conclusion: HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency.
Clinical Implications: HCT is a definitive cure for DADA2 with > 95% survival.
(© 2021. The Author(s).)
Databáze: MEDLINE
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