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A Nationwide Study of GATA2 Deficiency in Norway-the Majority of Patients Have Undergone Allo-HSCT.
Jørgensen, Silje F; Buechner, Jochen; Myhre, Anders E; Galteland, Eivind; Spetalen, Signe; Kulseth, Mari Ann; Sorte, Hanne S; Holla, Øystein L; Lundman, Emma; Alme, Charlotte; Heier, Ingvild; Flægstad, Trond; Fløisand, Yngvar; Benneche, Andreas; Fevang, Børre; Aukrust, Pål; Stray-Pedersen, Asbjørg; Gedde-Dahl, Tobias; Nordøy, Ingvild.
Afiliação
  • Jørgensen SF; Section of Clinical Immunology and Infectious Diseases, Department of Rheumatology, Dermatology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway. s.f.jorgensen@medisin.uio.no.
  • Buechner J; Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway. s.f.jorgensen@medisin.uio.no.
  • Myhre AE; Department of Paediatric Haematology and Oncology, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
  • Galteland E; Department of Haematology, Oslo University Hospital, Oslo, Norway.
  • Spetalen S; Department of Haematology, Oslo University Hospital, Oslo, Norway.
  • Kulseth MA; Department of Pathology, Oslo University Hospital, Oslo, Norway.
  • Sorte HS; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
  • Holla ØL; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
  • Lundman E; Department of Medical Genetics, Telemark Hospital, Skien, Norway.
  • Alme C; Norwegian National Unit for Newborn Screening, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
  • Heier I; Department of Paediatric Haematology and Oncology, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
  • Flægstad T; Department of Paediatric Haematology and Oncology, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
  • Fløisand Y; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.
  • Benneche A; Department of Paediatrics, University Hospital of North Norway, Tromsø, Norway.
  • Fevang B; Department of Haematology, The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK.
  • Aukrust P; Centre for Cancer Cell Reprogramming, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • Stray-Pedersen A; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
  • Gedde-Dahl T; Section of Clinical Immunology and Infectious Diseases, Department of Rheumatology, Dermatology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  • Nordøy I; Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
J Clin Immunol ; 42(2): 404-420, 2022 02.
Article em En | MEDLINE | ID: mdl-34893945
ABSTRACT

PURPOSE:

GATA2 deficiency is a rare primary immunodeficiency that has become increasingly recognized due to improved molecular diagnostics and clinical awareness. The only cure for GATA2 deficiency is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The inconsistency of genotype-phenotype correlations makes the decision regarding "who and when" to transplant challenging. Despite considerable morbidity and mortality, the reported proportion of patients with GATA2 deficiency that has undergone allo-HSCT is low (~ 35%). The purpose of this study was to explore if detailed clinical, genetic, and bone marrow characteristics could predict end-point outcome, i.e., death and allo-HSCT.

METHODS:

All medical genetics departments in Norway were contacted to identify GATA2 deficient individuals. Clinical information, genetic variants, treatment, and outcome were subsequently retrieved from the patients' medical records.

RESULTS:

Between 2013 and 2020, we identified 10 index cases or probands, four additional symptomatic patients, and no asymptomatic patients with germline GATA2 variants. These patients had a diverse clinical phenotype dominated by cytopenia (13/14), myeloid neoplasia (10/14), warts (8/14), and hearing loss (7/14). No valid genotype-phenotype correlations were found in our data set, and the phenotypes varied also within families. We found that 11/14 patients (79%), with known GATA2 deficiency, had already undergone allo-HSCT. In addition, one patient is awaiting allo-HSCT. The indications to perform allo-HSCT were myeloid neoplasia, disseminated viral infection, severe obliterating bronchiolitis, and/or HPV-associated in situ carcinoma. Two patients died, 8 months and 7 years after allo-HSCT, respectively.

CONCLUSION:

Our main conclusion is that the majority of patients with symptomatic GATA2 deficiency will need allo-HSCT, and a close surveillance of these patients is important to find the "optimal window" for allo-HSCT. We advocate a more offensive approach to allo-HSCT than previously described.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Células-Tronco Hematopoéticas / Deficiência de GATA2 Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans País/Região como assunto: Europa Idioma: En Revista: J Clin Immunol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Noruega

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Células-Tronco Hematopoéticas / Deficiência de GATA2 Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans País/Região como assunto: Europa Idioma: En Revista: J Clin Immunol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Noruega