title: Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006).
abstract: Adenosine deaminase (ADA) deficiency is a disorder of purine salvage that has its most devastating consequences in the immune system leading to severe combined immunodeficiency (SCID). Management options for ADA SCID include hematopoietic stem cell transplantation, enzyme replacement therapy and gene therapy. Formal data on the outcome following each of the three treatment modalities are limited, and this symposium was held in order to gather together the experience from major centers in Europe and the US. Transplantation for ADA-SCID is highly successful with survival rates of approximately 90% if a matched sibling or matched related donor is available but survival following matched unrelated donor or haploidentical procedures is 63% and 50% respectively with a significant rejection/non-engraftment rate in unconditioned procedures. Successfully transplanted patients demonstrated good immunological recovery with normal cellular and humoral function in the majority of cases. PEG-ADA has been used in over 150 patients worldwide either as an alternative to mismatched transplant or as a stabilizing measure prior to transplant. Overall, approximately two thirds of patients treated with PEG-ADA have survived with the majority of patients showing good clinical improvement. The level of immune recovery long term was less than that seen after transplant and approximately 50% of patients continued to receive immunoglobulin replacement. Gene therapy has been used as an experimental procedure in two centers in Europe. Early results from 9 patients suggest that the treatment is safe and that the majority have shown recovery of cellular immune function. Long-term follow-up of treated patients highlights a significant incidence of non-immunological problems with cognitive, neurological and audiological abnormalities most prominent.
authors.affiliation: Molecular Immunology Unit, Institute of Child Health, University College London, and Department of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London WC1N 3JH, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Booth
authors.forename: Mike
authors.initials: M
authors.lastname: Hershfield
authors.forename: Luigi
authors.initials: L
authors.lastname: Notarangelo
authors.forename: Rebecca
authors.initials: R
authors.lastname: Buckley
authors.forename: Manfred
authors.initials: M
authors.lastname: Hoenig
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Aiuti
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
mesh_terms: D000243:Adenosine Deaminase / Q000009:adverse effects / Q000172:deficiency* / Q000627:therapeutic use; D000328:Adult; D002648:Child; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000243:Adenosine Deaminase; C051409:pegademase bovine