HLA-mismatched unrelated donors are a viable alternate graft source for allogeneic transplantation following alemtuzumab-based reduced-intensity conditioning.
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.
Mead
Adam J
AJ
Department of Haematology, University College London (UCL) Medical School, London, United Kingdom.
Thomson
Kirsty J
KJ
Morris
Emma C
EC
Mohamedbhai
Sajir
S
Denovan
Shari
S
Orti
Guillermo
G
Fielding
Adele K
AK
Kottaridis
Panagiotis D
PD
Hough
Rachael
R
Chakraverty
Ronjon
R
Linch
David C
DC
Mackinnon
Stephen
S
Peggs
Karl S
KS
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
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