title: A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: 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, Freiburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Speckmann
authors.affiliation: Institute for Medical Biometry and Statistics, Center for Medical Biometry and Medical Informatics, Medical Center - University of Freiburg, Freiburg, Germany.
authors.forename: Sam
authors.initials: S
authors.lastname: Doerken
authors.affiliation: 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.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Aiuti
authors.affiliation: Dr von Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Albert
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
authors.forename: Waleed
authors.initials: W
authors.lastname: Al-Herz
authors.affiliation: Servicio de Inmunología, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Allende
authors.affiliation: Department of Pediatrics, Ospedale Pediatrico Bambino Gesù and University of Rome "Tor Vergata," Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Scarselli
authors.affiliation: Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center, Ljubljana, Slovenia.
authors.forename: Tadej
authors.initials: T
authors.lastname: Avcin
authors.affiliation: Center for Pediatrics and Adolescent Medicine, Helios Hospital Krefeld, Krefeld, Germany.
authors.forename: Ruy
authors.initials: R
authors.lastname: Perez-Becker
authors.affiliation: Department of Pediatrics, Ospedale Pediatrico Bambino Gesù and University of Rome "Tor Vergata," Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cancrini
authors.affiliation: Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cant
authors.affiliation: Department of Pediatrics, Ospedale Pediatrico Bambino Gesù and University of Rome "Tor Vergata," Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Cesare
authors.affiliation: Department of Pediatrics, Ospedale Pediatrico Bambino Gesù and University of Rome "Tor Vergata," Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Finocchi
authors.affiliation: AP-HP, Hôpital Necker-Enfants Malades, Immunologie et Hématologie Pédiatriques, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Department of Immunology, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Sujal
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gennery
authors.affiliation: Department of Immunology, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Gilmour
authors.affiliation: 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.
authors.forename: Luis I
authors.initials: LI
authors.lastname: González-Granado
authors.affiliation: Immunology Division, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Martinez-Gallo
authors.affiliation: Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Sophie
authors.initials: S
authors.lastname: Hambleton
authors.affiliation: Immunodeficiency Unit and Immunological Diagnostics Laboratory, Dr von Hauner Children's Hospital Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Hauck
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Hoenig
authors.affiliation: 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.
authors.forename: Despina
authors.initials: D
authors.lastname: Moshous
authors.affiliation: AP-HP, Hôpital Necker-Enfants Malades, Immunologie et Hématologie Pédiatriques, Paris, France.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Neven
authors.affiliation: Center for Pediatrics and Adolescent Medicine, Helios Hospital Krefeld, Krefeld, Germany.
authors.forename: Tim
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authors.lastname: Niehues
authors.affiliation: Division of Immunology, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Mass.
authors.forename: Luigi
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authors.lastname: Notarangelo
authors.affiliation: 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.
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.affiliation: Department of Pediatrics I, University of Tübingen, Tübingen, Germany; Department of Pediatrics, StKM GmbH and Technical University Muenchen, Munich, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Rieber
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schulz
authors.affiliation: 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.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schwarz
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology-Oncology, Medical University Graz, Graz, Austria.
authors.forename: Markus G
authors.initials: MG
authors.lastname: Seidel
authors.affiliation: Immunology Division, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Soler-Palacin
authors.affiliation: Pediatric Hematology-Oncology and Bone Marrow Transplantation, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Polina
authors.initials: P
authors.lastname: Stepensky
authors.affiliation: Department of Pediatric Hematology and Oncology, Center for Pediatrics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Strahm
authors.affiliation: Department of Pediatric Hematology and Oncology, Center for Pediatrics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vraetz
authors.affiliation: Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Warnatz
authors.affiliation: 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.
authors.forename: Christine
authors.initials: C
authors.lastname: Winterhalter
authors.affiliation: Department of Immunology, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
authors.forename: Austen
authors.initials: A
authors.lastname: Worth
authors.affiliation: Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: 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.
authors.forename: Annette
authors.initials: A
authors.lastname: Uhlmann
authors.affiliation: 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, Freiburg, Germany. Electronic address: stephan.ehl@uniklinik-freiburg.de.
authors.forename: Stephan
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authors.lastname: Ehl
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D012107:Research Design; D016511:Severe Combined Immunodeficiency / Q000276:immunology* / Q000473:pathology* / Q000628:therapy*
keywords: T-cell deficiency; combined immunodeficiency; hematopoietic stem cell transplantation; natural history