title: Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency.
abstract: BACKGROUND
  Common variable immunodeficiency (CVID) is usually well controlled with immunoglobulin substitution and immunomodulatory drugs. A subgroup of patients has a complicated disease course with high mortality. For these patients, investigation of more invasive, potentially curative treatments, such as allogeneic hematopoietic stem cell transplantation (HSCT), is warranted.
  
  
  OBJECTIVE
  We sought to define the outcomes of HSCT for patients with CVID.
  
  
  METHODS
  Retrospective data were collected from 14 centers worldwide on patients with CVID receiving HSCT between 1993 and 2012.
  
  
  RESULTS
  Twenty-five patients with CVID, which was defined according to international criteria, aged 8 to 50 years at the time of transplantation were included in the study. The indication for HSCT was immunologic dysregulation in the majority of patients. The overall survival rate was 48%, and the survival rate for patients undergoing transplantation for lymphoma was 83%. The major causes of death were treatment-refractory graft-versus-host disease accompanied by poor immune reconstitution and infectious complications. Immunoglobulin substitution was stopped in 50% of surviving patients. In 92% of surviving patients, the condition constituting the indication for HSCT resolved.
  
  
  CONCLUSIONS
  This multicenter study demonstrated that HSCT in patients with CVID was beneficial in most surviving patients; however, there was a high mortality associated with the procedure. Therefore this therapeutic approach should only be considered in carefully selected patients in whom there has been extensive characterization of the immunologic and/or genetic defect underlying the CVID diagnosis. Criteria for patient selection, refinement of the transplantation protocol, and timing are needed for an improved outcome.
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg and the University of Freiburg, Freiburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Wehr
authors.affiliation: Department of Paediatric Immunology, Newcastle Upon Tyne Hospitals Foundation Trust, Newcastle Upon Tyne, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gennery
authors.affiliation: Pediatric Blood and Bone Marrow Transplantation Program, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lindemans
authors.affiliation: Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Hoenig
authors.affiliation: Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Marks
authors.affiliation: Clinic for Primary Immunodeficiency, Medical Outpatient Clinic and Immunodeficiency Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland.
authors.forename: Mike
authors.initials: M
authors.lastname: Recher
authors.affiliation: Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, Jena, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Gruhn
authors.affiliation: Division of Hematology and Stem Cell Transplant Team, University Hospital Basel, Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Holbro
authors.affiliation: Medical Immunology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Heijnen
authors.affiliation: University Children's Hospital, Zurich, Switzerland.
authors.forename: Deborah
authors.initials: D
authors.lastname: Meyer
authors.affiliation: Department of Hematology/Oncology, University Medical Center Würzburg, Würzburg, Germany.
authors.forename: Goetz
authors.initials: G
authors.lastname: Grigoleit
authors.affiliation: Department of Hematology/Oncology, University Medical Center Würzburg, Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Paediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
authors.affiliation: Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Witte
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Hannover, Hannover, Germany.
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Sykora
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg and the University of Freiburg, Freiburg, Germany.
authors.forename: Sigune
authors.initials: S
authors.lastname: Goldacker
authors.affiliation: Unidad de Immunología, Hospital de Niños Sor María Ludovica La Plata, Buenos Aires, Argentina.
authors.forename: Lorena
authors.initials: L
authors.lastname: Regairaz
authors.affiliation: Department of Pediatric Hematology & Oncology and BMT Center, Ege University, Bornova-Izmir, Turkey.
authors.forename: Serap
authors.initials: S
authors.lastname: Aksoylar
authors.affiliation: Division of Allergy and Clinical Immunology, Ege University Medical Faculty, Izmir, Turkey.
authors.forename: Ömur
authors.initials: Ö
authors.lastname: Ardeniz
authors.affiliation: Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.affiliation: Lower Silesian Center for Cellular Transplantation, Wroclaw, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Zdziarski
authors.affiliation: Department of Paediatrics, University Hospital Leuven, Leuven, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meyts
authors.affiliation: St Anna Kinderspital, Medical University, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Matthes-Martin
authors.affiliation: Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Imai
authors.affiliation: Department of Pediatrics, National Defense Medical College, Saitama, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Kamae
authors.affiliation: University College London, London, United Kingdom.
authors.forename: Adele
authors.initials: A
authors.lastname: Fielding
authors.affiliation: Immunology Department, Royal Free London, London, United Kingdom.
authors.forename: Suranjith
authors.initials: S
authors.lastname: Seneviratne
authors.affiliation: Unité d'Immuno-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, French National Reference Center for PIDs (CEREDIH), Stem Cell Transplantation for PIDs in Europe (SCETIDE) registry, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Slatter
authors.affiliation: University Children's Hospital, Zurich, Switzerland.
authors.forename: Tayfun
authors.initials: T
authors.lastname: Güngör
authors.affiliation: University of Manchester, Royal Manchester Children's Hospital, Manchester, United Kingdom.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Arkwright
authors.affiliation: Pediatric Immunology and Infectious Disease, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Joris
authors.initials: J
authors.lastname: van Montfrans
authors.affiliation: Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg and the University of Freiburg, Freiburg, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
authors.affiliation: Department of Paediatric Immunology, Newcastle Upon Tyne Hospitals Foundation Trust, Newcastle Upon Tyne, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cant
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg and the University of Freiburg, Freiburg, Germany.
authors.forename: Hans-Hartmut
authors.initials: HH
authors.lastname: Peter
authors.affiliation: Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Finke
authors.affiliation: Center of Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, London, United Kingdom.
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg and the University of Freiburg, Freiburg, Germany. Electronic address: klaus.warnatz@uniklinik-freiburg.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Warnatz
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg and the University of Freiburg, Freiburg, Germany. Electronic address: marta.rizzi@uniklinik-freiburg.de.
authors.forename: Marta
authors.initials: M
authors.lastname: Rizzi
mesh_terms: D000293:Adolescent; D000328:Adult; D002423:Cause of Death; D002648:Child; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000401:mortality / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D055815:Young Adult
keywords: Common variable immunodeficiency; hematopoietic stem cell transplantation; hypogammaglobulinemia; immunoglobulin substitution/replacement; immunologic reconstitution; mortality; outcome; survival