title: Excellent outcome of matched unrelated donor transplantation in paediatric aplastic anaemia following failure with immunosuppressive therapy: a United Kingdom multicentre retrospective experience.
abstract: We retrospectively analysed the outcome of consecutive children with idiopathic severe aplastic anaemia in the United Kingdom who received immunosuppressive therapy (IST) or matched unrelated donor (MUD) haematopoietic stem cell transplantation (HSCT). The 6-month cumulative response rate following rabbit antithymocyte globulin (ATG)/ciclosporin (IST) was 32·5% (95% CI 19·3-46·6) (n = 43). The 5-year estimated failure-free survival (FFS) following IST was 13·3% (95% confidence interval [CI] 4·0-27·8). In contrast, in 44 successive children who received a 10-antigen (HLA-A, -B, -C, -DRB1, -DQB1) MUD HSCT there was an excellent estimated 5-year FFS of 95·01% (95% CI 81·38-98·74). Forty of these children had failed IST previously. HSCT conditioning was a fludarabine, cyclophosphamide and alemtuzumab (FCC) regimen and did not include radiotherapy. There were no cases of graft failure. Median donor chimerism was 100% (range 88-100%). A conditioning regimen, such as FCC that avoids total body irradiation is ideally suited in children. Our data suggest that MUD HSCT following IST failure offers an excellent outcome and furthermore, if a suitable MUD can be found quickly, MUD HSCT may be a reasonable alternative to IST.
authors.affiliation: Department of Paediatric & Adolescent Haematology, Great North Children's Hospital, Newcastle upon Tyne, UK.
authors.forename: Sujith
authors.initials: S
authors.lastname: Samarasinghe
authors.forename: Colin
authors.initials: C
authors.lastname: Steward
authors.forename: Prashant
authors.initials: P
authors.lastname: Hiwarkar
authors.forename: Muhammad Ameer
authors.initials: MA
authors.lastname: Saif
authors.forename: Rachael
authors.initials: R
authors.lastname: Hough
authors.forename: David
authors.initials: D
authors.lastname: Webb
authors.forename: Alice
authors.initials: A
authors.lastname: Norton
authors.forename: Sarah
authors.initials: S
authors.lastname: Lawson
authors.forename: Amrana
authors.initials: A
authors.lastname: Qureshi
authors.forename: Philip
authors.initials: P
authors.lastname: Connor
authors.forename: Peter
authors.initials: P
authors.lastname: Carey
authors.forename: Rod
authors.initials: R
authors.lastname: Skinner
authors.forename: Ajay
authors.initials: A
authors.lastname: Vora
authors.forename: Maria
authors.initials: M
authors.lastname: Pelidis
authors.forename: Brenda
authors.initials: B
authors.lastname: Gibson
authors.forename: Graham
authors.initials: G
authors.lastname: Stewart
authors.forename: Steve
authors.initials: S
authors.lastname: Keogh
authors.forename: Nick
authors.initials: N
authors.lastname: Goulden
authors.forename: Denise
authors.initials: D
authors.lastname: Bonney
authors.forename: Mathew
authors.initials: M
authors.lastname: Stubbs
authors.forename: Persis
authors.initials: P
authors.lastname: Amrolia
authors.forename: Kanchan
authors.initials: K
authors.lastname: Rao
authors.forename: Stefan
authors.initials: S
authors.lastname: Meyer
authors.forename: Rob
authors.initials: R
authors.lastname: Wynn
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009894:Opportunistic Infections / Q000209:etiology; D012008:Recurrence; D012189:Retrospective Studies; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D017211:Treatment Failure; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine