title: Outcomes of alemtuzumab-based reduced intensity conditioning stem cell transplantation using unrelated donors for myelodysplastic syndromes.
abstract: This prospective study evaluated the outcomes of 75 successive patients receiving a FBC (fludarabine, busulphan, alemtuzumab) reduced-intensity conditioning (RIC) regimen for myelodysplastic syndromes (MDS) using volunteer unrelated donors(VUD). The prognostic significance of a variety of clinical variables including the recently described haematopoietic cell transplantation co-morbidity index (HCT-CI) was assessed. The median age of the cohort was 52.0 years (range: 19-68 years) with a median follow-up of 1038.5 d. Forty-nine patients (65%) had an International Prognostic Scoring System stage of > or = Intermediate-2, 35 (46%) had intermediate or poor risk cytogenetics, and 23 patients(31%) were human leucocyte antigen-mismatched. The actuarial 3-year overall survival (OS) and disease-free survival (DFS) was 43% [95% confidence interval (CI): 37-49] and 41% (95%CI: 35-47) respectively, and the cumulative incidence of extensive chronic graft-versus-host disease was 22%. On multivariate analysis, presence of either one class II mismatch or a two-antigen mismatch adversely influenced transplant-related mortality, DFS and OS. In addition, disease status at transplantation and the haematopoietic cell transplantation-specific comorbidity index were independent variables for overall survival. In contrast, both advanced age and pre-transplant cytogenetic status did not significantly affect overall outcomes. RIC regimens using VUD was associated with durable long-term survival even in older patients with MDS, and the use of a pre-transplant comorbidity index may help to improve patient selection for transplantation.
authors.affiliation: Department of Haematological Medicine, Kings College London and Kings College Hospital, UK.
authors.forename: Zi Yi
authors.initials: ZY
authors.lastname: Lim
authors.forename: Aloysius Y L
authors.initials: AY
authors.lastname: Ho
authors.forename: Wendy
authors.initials: W
authors.lastname: Ingram
authors.forename: Michelle
authors.initials: M
authors.lastname: Kenyon
authors.forename: Laurence
authors.initials: L
authors.lastname: Pearce
authors.forename: Barbara
authors.initials: B
authors.lastname: Czepulkowski
authors.forename: Stephen
authors.initials: S
authors.lastname: Devereux
authors.forename: Rafael F
authors.initials: RF
authors.lastname: Duarte
authors.forename: Antonio
authors.initials: A
authors.lastname: Pagliuca
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D004812:Epidemiologic Methods; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000628:therapy*; D011379:Prognosis; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine