title: Cyclosporin A response and dependence in children with acquired aplastic anaemia: a multicentre retrospective study with long-term observation follow-up.
abstract: Immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin A (CyA) is the standard treatment for children with acquired aplastic anaemia (AAA) lacking a matched donor. Survival rates of more than 80% at 5 years are achieved, but the response is drug-dependent in 15-25% of cases. This study, of 42 consecutive children with AAA treated with IST, assessed the incidence of CyA-dependence, CyA and granulocyte colony-stimulating factor (G-CSF) tapering schedules and the impact of drug accumulation on progression to myelodysplasia/acute myeloid leukaemia (MDS/AML). Overall survival was 83% at 10 years. CyA-dependence without a predictive marker was observed in 18% of responders. Probability of discontinuing CyA was 60.5% at 10 years; a slow CyA tapering schedule was performed in 84% of patients; the cumulative incidence of relapse was 16% at 10 years. Relapse risk was significantly associated with rapid CyA discontinuation: 60% compared to 7.6% in the slow tapering group (P = 0.001). Cumulative incidence of MDS/AML was 8% at 10 years, with a significant correlation with both G-CSF cumulative dose and second IST. This long-term follow-up of children with AAA shows that IST with a slow CyA tapering course is an effective treatment with a low-relapse rate in these cases.
authors.affiliation: Paediatric Haematology, University of Turin, Turin, Italy. paola.saracco@unito.it
authors.forename: Paola
authors.initials: P
authors.lastname: Saracco
authors.forename: Paola
authors.initials: P
authors.lastname: Quarello
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Iori
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.forename: Daniela
authors.initials: D
authors.lastname: Longoni
authors.forename: Johanna
authors.initials: J
authors.lastname: Svahn
authors.forename: Stefania
authors.initials: S
authors.lastname: Varotto
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Del Vecchio
authors.forename: Carlo
authors.initials: C
authors.lastname: Dufour
authors.forename: Ugo
authors.initials: U
authors.lastname: Ramenghi
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: Anna
authors.initials: A
authors.lastname: Locasciulli
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000097:blood / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine