title: KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia.
abstract: Donor killer cell immunoglobulin-like receptor (KIR)-ligand incompatibility is associated with decreased relapse incidence (RI) and improved leukemia-free survival (LFS) after haploidentical and HLA-mismatched unrelated hematopoietic stem cell transplantation. We assessed outcomes of 218 patients with acute myeloid leukemia (AML n=94) or acute lymphoblastic leukemia (n=124) in complete remission (CR) who had received a single-unit unrelated cord blood transplant (UCBT) from a KIR-ligand-compatible or -incompatible donor. Grafts were HLA-A, -B or -DRB1 matched (n=21) or mismatched (n=197). Patients and donors were categorized according to their degree of KIR-ligand compatibility in the graft-versus-host direction by determining whether or not they expressed HLA-C group 1 or 2, HLA-Bw4 or HLA-A3/-A11. Both HLA-C/-B KIR-ligand- and HLA-A-A3/-A11 KIR-ligand-incompatible UCBT showed a trend to improved LFS (P=0.09 and P=0.13, respectively). Sixty-nine donor-patient pairs were HLA-A, -B or -C KIR-ligand incompatible and 149 compatible. KIR-ligand-incompatible UCBT showed improved LFS (hazards ratio=2.05, P=0.0016) and overall survival (OS) (hazards ratio=2.0, P=0.004) and decreased RI (hazards ratio=0.53, P=0.05). These results were more evident for AML transplant recipients (2-year LFS and RI with or without KIR-ligand incompatibility 73 versus 38% (P=0.012), and 5 versus 36% (P=0.005), respectively). UCBT for acute leukemia in CR from KIR-ligand-incompatible donors is associated with decreased RI and improved LFS and OS.
authors.affiliation: Clinical Research Unit, Eurocord Office, APHP, Hôpital Saint Louis, Université de Paris VII, Paris, France. r.willemze@lumc.nl
authors.forename: R
authors.initials: R
authors.lastname: Willemze
authors.forename: C A
authors.initials: CA
authors.lastname: Rodrigues
authors.forename: M
authors.initials: M
authors.lastname: Labopin
authors.forename: G
authors.initials: G
authors.lastname: Sanz
authors.forename: G
authors.initials: G
authors.lastname: Michel
authors.forename: G
authors.initials: G
authors.lastname: Socié
authors.forename: B
authors.initials: B
authors.lastname: Rio
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authors.initials: A
authors.lastname: Sirvent
authors.forename: M
authors.initials: M
authors.lastname: Renaud
authors.forename: L
authors.initials: L
authors.lastname: Madero
authors.forename: M
authors.initials: M
authors.lastname: Mohty
authors.forename: C
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authors.lastname: Ferra
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authors.lastname: Garnier
authors.forename: P
authors.initials: P
authors.lastname: Loiseau
authors.forename: J
authors.initials: J
authors.lastname: Garcia
authors.forename: L
authors.initials: L
authors.lastname: Lecchi
authors.forename: G
authors.initials: G
authors.lastname: Kögler
authors.forename: Y
authors.initials: Y
authors.lastname: Beguin
authors.forename: C
authors.initials: C
authors.lastname: Navarrete
authors.forename: T
authors.initials: T
authors.lastname: Devos
authors.forename: I
authors.initials: I
authors.lastname: Ionescu
authors.forename: K
authors.initials: K
authors.lastname: Boudjedir
authors.forename: A-L
authors.initials: AL
authors.lastname: Herr
authors.forename: E
authors.initials: E
authors.lastname: Gluckman
authors.forename: V
authors.initials: V
authors.lastname: Rocha
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000502:physiology; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology; D007938:Leukemia / Q000276:immunology / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000276:immunology; D012074:Remission Induction; D012189:Retrospective Studies; D014184:Transplantation, Homologous / Q000276:immunology; D016896:Treatment Outcome; D014775:Virus Activation; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D054340:Receptors, KIR