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A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis.
Speckmann, Carsten; Doerken, Sam; Aiuti, Alessandro; Albert, Michael H; Al-Herz, Waleed; Allende, Luis M; Scarselli, Alessia; Avcin, Tadej; Perez-Becker, Ruy; Cancrini, Caterina; Cant, Andrew; Di Cesare, Silvia; Finocchi, Andrea; Fischer, Alain; Gaspar, H Bobby; Ghosh, Sujal; Gennery, Andrew; Gilmour, Kimberly; González-Granado, Luis I; Martinez-Gallo, Monica; Hambleton, Sophie; Hauck, Fabian; Hoenig, Manfred; Moshous, Despina; Neven, Benedicte; Niehues, Tim; Notarangelo, Luigi; Picard, Capucine; Rieber, Nikolaus; Schulz, Ansgar; Schwarz, Klaus; Seidel, Markus G; Soler-Palacin, Pere; Stepensky, Polina; Strahm, Brigitte; Vraetz, Thomas; Warnatz, Klaus; Winterhalter, Christine; Worth, Austen; Fuchs, Sebastian; Uhlmann, Annette; Ehl, Stephan.
Affiliation
  • Speckmann C; Department of Pediatric Hematology and Oncology, Center for Pediatrics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg,
  • Doerken S; Institute for Medical Biometry and Statistics, Center for Medical Biometry and Medical Informatics, Medical Center - University of Freiburg, Freiburg, Germany.
  • Aiuti A; Pediatric Immunohematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute, Milan, Italy; Department of Pediatrics, Ospedale Pediatrico Bambino Gesù and University of Rome "Tor Vergata," Rome, Italy.
  • Albert MH; Dr von Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany.
  • Al-Herz W; Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
  • Allende LM; Servicio de Inmunología, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain.
  • Scarselli A; Department of Pediatrics, Ospedale Pediatrico Bambino Gesù and University of Rome "Tor Vergata," Rome, Italy.
  • Avcin T; Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center, Ljubljana, Slovenia.
  • Perez-Becker R; Center for Pediatrics and Adolescent Medicine, Helios Hospital Krefeld, Krefeld, Germany.
  • Cancrini C; Department of Pediatrics, Ospedale Pediatrico Bambino Gesù and University of Rome "Tor Vergata," Rome, Italy.
  • Cant A; Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Di Cesare S; Department of Pediatrics, Ospedale Pediatrico Bambino Gesù and University of Rome "Tor Vergata," Rome, Italy.
  • Finocchi A; Department of Pediatrics, Ospedale Pediatrico Bambino Gesù and University of Rome "Tor Vergata," Rome, Italy.
  • Fischer A; AP-HP, Hôpital Necker-Enfants Malades, Immunologie et Hématologie Pédiatriques, Paris, France.
  • Gaspar HB; Department of Immunology, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
  • Ghosh S; Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, Düsseldorf, Germany.
  • Gennery A; Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Gilmour K; Department of Immunology, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
  • González-Granado LI; Servicio de Inmunología, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain; Immunodeficiencies Unit, Hematology & Oncology Unit, Pediatrics, Hospital 12 Octubre, Madrid, Spain.
  • Martinez-Gallo M; Immunology Division, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Hambleton S; Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Hauck F; Immunodeficiency Unit and Immunological Diagnostics Laboratory, Dr von Hauner Children's Hospital Ludwig-Maximilians-University, Munich, Germany.
  • Hoenig M; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Moshous D; AP-HP, Hôpital Necker-Enfants Malades, Immunologie et Hématologie Pédiatriques, Paris, France; INSERM UMR1163, Genome Dynamics in the Immune System, Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, Paris, France.
  • Neven B; AP-HP, Hôpital Necker-Enfants Malades, Immunologie et Hématologie Pédiatriques, Paris, France.
  • Niehues T; Center for Pediatrics and Adolescent Medicine, Helios Hospital Krefeld, Krefeld, Germany.
  • Notarangelo L; Division of Immunology, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Mass.
  • Picard C; AP-HP, Hôpital Necker-Enfants Malades, Immunologie et Hématologie Pédiatriques, Paris, France; INSERM UMR1163, Genome Dynamics in the Immune System, Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, Paris, France.
  • Rieber N; Department of Pediatrics I, University of Tübingen, Tübingen, Germany; Department of Pediatrics, StKM GmbH and Technical University Muenchen, Munich, Germany.
  • Schulz A; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Schwarz K; Institute for Transfusion Medicine, University of Ulm, and the Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Service, Baden-Württemberg-Hessen, Ulm, Germany.
  • Seidel MG; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology-Oncology, Medical University Graz, Graz, Austria.
  • Soler-Palacin P; Immunology Division, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Stepensky P; Pediatric Hematology-Oncology and Bone Marrow Transplantation, Hadassah Hebrew University Hospital, Jerusalem, Israel.
  • Strahm B; Department of Pediatric Hematology and Oncology, Center for Pediatrics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Vraetz T; Department of Pediatric Hematology and Oncology, Center for Pediatrics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Warnatz K; Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Winterhalter C; Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Clinical Trials Unit, Medical Center - University of Freiburg, Freiburg, Germany.
  • Worth A; Department of Immunology, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
  • Fuchs S; Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Uhlmann A; Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Clinical Trials Unit, Medical Center - University of Freiburg, Freiburg, Germany.
  • Ehl S; Department of Pediatric Hematology and Oncology, Center for Pediatrics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg,
J Allergy Clin Immunol ; 139(4): 1302-1310.e4, 2017 Apr.
Article in En | MEDLINE | ID: mdl-27658761
BACKGROUND: Absent T-cell immunity resulting in life-threatening infections provides a clear rationale for hematopoetic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency (SCID). Combined immunodeficiencies (CIDs) and "atypical" SCID show reduced, not absent T-cell immunity. If associated with infections or autoimmunity, they represent profound combined immunodeficiency (P-CID), for which outcome data are insufficient for unambiguous early transplant decisions. OBJECTIVES: We sought to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. METHODS: In this prospective and retrospective observational study, we recruited nontransplanted patients with P-CID aged 1 to 16 years to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. RESULTS: A total of 51 patients were recruited (median age, 9.6 years). Thirteen of 51 had a genetic diagnosis of "atypical" SCID and 14 of 51 of CID. About half of the patients had less than 10% naive T cells, reduced/absent T-cell proliferation, and at least 1 significant clinical event/year, demonstrating their profound immunodeficiency. Nineteen patients (37%) underwent transplantation within 1 year of enrolment, and 5 of 51 patients died. Analysis of the HSCT decisions revealed the anticipated heterogeneity, favoring an ongoing prospective matched-pair analysis of patients with similar disease severity with or without transplantation. Importantly, so far neither the genetic diagnosis nor basic measurements of T-cell immunity were good predictors of disease evolution. CONCLUSIONS: The P-CID study for the first time characterizes a group of patients with nontypical SCID T-cell deficiencies from a therapeutic perspective. Because genetic and basic T-cell parameters provide limited guidance, prospective data from this study will be a helpful resource for guiding the difficult HSCT decisions in patients with P-CID.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Severe Combined Immunodeficiency / Hematopoietic Stem Cell Transplantation Type of study: Clinical_trials / Guideline / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male Language: En Journal: J Allergy Clin Immunol Year: 2017 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Severe Combined Immunodeficiency / Hematopoietic Stem Cell Transplantation Type of study: Clinical_trials / Guideline / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male Language: En Journal: J Allergy Clin Immunol Year: 2017 Document type: Article Country of publication: United States