title: HLA-mismatched unrelated donors are a viable alternate graft source for allogeneic transplantation following alemtuzumab-based reduced-intensity conditioning.
abstract: The impact of human leukocyte antigen (HLA) mismatch after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIT) using unrelated donors (UD) is unclear, and may be modulated by T-cell depletion. We therefore examined outcomes of 157 consecutive patients undergoing RIT after uniform conditioning with fludarabine, melphalan, and alemtuzumab (FMC). Donors were 10/10 HLA-matched (MUDs, n = 107) and 6 to 9/10 HLA-matched (MMUDs, n = 50), with no significant differences in baseline characteristics other than increased cytomegalovirus seropositivity in MMUDs. Rates of durable engraftment were high. Graft failure rates (persistent cytopenias with donor chimerism) were similar (8% vs 3%, P = .21), though rejection (recipient chimerism) was more frequent in MMUDs (8% vs 0%, P < .01). There were no significant differences between donors in the incidences of acute graft-versus-host disease (GVHD; 20% vs 22% grade 2-4, respectively, P = .83), chronic extensive GVHD (3-year cumulative incidence [CI] 23% vs 24%, P = .56), or treatment-related mortality (1-year CI 27% vs 27%, P = .96). Furthermore, there was no difference in 3-year overall survival (OS; 53% vs 49%, P = .44). Mismatch occurred at the antigenic level in 40 cases. The outcome in these cases did not differ significantly from the rest of the cohort. We conclude that RIT using HLA-mismatched grafts is a viable option using FMC conditioning.
authors.affiliation: Department of Haematology, University College London (UCL) Medical School, London, United Kingdom.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Mead
authors.forename: Kirsty J
authors.initials: KJ
authors.lastname: Thomson
authors.forename: Emma C
authors.initials: EC
authors.lastname: Morris
authors.forename: Sajir
authors.initials: S
authors.lastname: Mohamedbhai
authors.forename: Shari
authors.initials: S
authors.lastname: Denovan
authors.forename: Guillermo
authors.initials: G
authors.lastname: Orti
authors.forename: Adele K
authors.initials: AK
authors.lastname: Fielding
authors.forename: Panagiotis D
authors.initials: PD
authors.lastname: Kottaridis
authors.forename: Rachael
authors.initials: R
authors.lastname: Hough
authors.forename: Ronjon
authors.initials: R
authors.lastname: Chakraverty
authors.forename: David C
authors.initials: DC
authors.lastname: Linch
authors.forename: Stephen
authors.initials: S
authors.lastname: Mackinnon
authors.forename: Karl S
authors.initials: KS
authors.lastname: Peggs
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002908:Chronic Disease; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection / Q000401:mortality; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000401:mortality / Q000628:therapy; D006680:HLA Antigens; D019337:Hematologic Neoplasms / Q000401:mortality* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015994:Incidence; D019520:Living Donors; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D006680:HLA Antigens; D019653:Myeloablative Agonists; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan