title: Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation.
abstract: Natural killer cells are regulated by killer cell immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n = 612) lacking ≥ 1 KIR ligands experienced higher grade III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95% CI, 1.16 to 2.28; P = .005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P = .002) and III to IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2(+) patients. AML patients with KIR2DS1(+), HLA-C2 homozygous donors had greater treatment-related mortality compared with others (HR, 2.4; 95% CI, 1.4 to 4.2; P = .002) but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor-activating KIRs or centromeric KIR content or for any donor-recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n = 297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT.
authors.affiliation: Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: sobeckr@ccf.org.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Sobecks
authors.affiliation: Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Transplant Center, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Medhat
authors.initials: M
authors.lastname: Askar
authors.affiliation: The Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Meighan M
authors.initials: MM
authors.lastname: Gallagher
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Michael
authors.initials: M
authors.lastname: Haagenson
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez-Vina
authors.affiliation: Oslo University Hospital, Oslo, Norway.
authors.forename: Karl-Johan
authors.initials: KJ
authors.lastname: Malmberg
authors.affiliation: Zentrales Knochenmarkspender-Register Deutschland, Ulm, Germany.
authors.forename: Carlheinz
authors.initials: C
authors.lastname: Müller
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Minoo
authors.initials: M
authors.lastname: Battiwalla
authors.affiliation: Division of Hematology & Medical Oncology, Center for Hematologic Malignancies, Oregon Health and Science University, Portland, Oregon.
authors.forename: James
authors.initials: J
authors.lastname: Gajewski
authors.affiliation: Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
authors.affiliation: Department of Therapeutic Immunology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.affiliation: Department of Pathology, University of Chicago Hospitals, Chicago, Illinois.
authors.forename: Susana
authors.initials: S
authors.lastname: Marino
authors.affiliation: Department of Pediatrics, Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital, Cincinnati, Ohio.
authors.forename: Stella
authors.initials: S
authors.lastname: Davies
authors.affiliation: Immunogenetic Operations and Research, National Marrow Donor Program, Minneapolis, Minnesota.
authors.forename: Jason
authors.initials: J
authors.lastname: Dehn
authors.affiliation: Universitatsklinikum Carl Gustav Carus, Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inamoto
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Pediatrics, University of Washington, Seattle, Washington.
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.affiliation: The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Shaw
authors.affiliation: Department of Pathology, Histocompatibility and Immunogenetics Laboratory, Children's Hospital, Oakland, California.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Pollack
authors.affiliation: Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weisdorf
authors.affiliation: Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Milller
authors.affiliation: Department of Oncology, Georgetown University Hospital, Washington, DC.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Hurley
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Katharine
authors.initials: K
authors.lastname: Hsu
mesh_terms: D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics / Q000401:mortality / Q000517:prevention & control; D015236:HLA-C Antigens / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000401:mortality / Q000628:therapy; D054342:Receptors, KIR2DL1 / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning
chemical_list: D015236:HLA-C Antigens; C048767:HLA-C*02 antigen; C093100:KIR2DL1 protein, human; D054342:Receptors, KIR2DL1
keywords: AML/MDS; Killer immunoglobulin-like receptor (KIR); Reduced-intensity conditioning HCT