title: Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation.
abstract: The ability of cord blood transplantation (CBT) to prevent relapse depends partly on donor natural killer (NK) cell alloreactivity. NK effector function depends on specific killer-cell immunoglobulin-like receptors (KIR) and HLA interactions. Thus, it is important to identify optimal combinations of KIR-HLA genotypes in donors and recipients that could improve CBT outcome. We studied clinical data, KIR and HLA genotypes, and NK-cell reconstitution in CBT patients (n = 110). Results were validated in an independent cohort (n = 94). HLA-KIR genotyping of recipient germline and transplanted cord blood (CB) grafts predicted for large differences in outcome. Patients homozygous for HLA-C2 group alleles had higher 1-year relapse rate and worse survival after CBT than did HLA-C1/C1 or HLA-C1/C2 (HLA-C1/x) patients: 67.8% vs 26.0% and 15.0% vs 52.9%, respectively. This inferior outcome was associated with delayed posttransplant recovery of NK cells expressing the HLA-C2-specific KIR2DL1/S1 receptors. HLA-C1/x patients receiving a CB graft with the combined HLA-C1-KIR2DL2/L3/S2 genotype had lower 1-year relapse rate (6.7% vs 40.1%) and superior survival (74.2% vs 41.3%) compared with recipients of grafts lacking KIR2DS2 or HLA-C1 HLA-C2/C2 patients had lower relapse rate (44.7% vs 93.4%) and better survival (30.1% vs 0%) if they received a graft with the combined HLA-C2-KIR2DL1/S1 genotype. Relapsed/refractory disease at CBT, recipient HLA-C2/C2 genotype, and donor HLA-KIR genotype were independent predictors of outcome. Thus, we propose the inclusion of KIR genotyping in graft selection criteria for CBT. HLA-C1/x patients should receive an HLA-C1-KIR2DL2/L3/S2 CB graft, while HLA-C2/C2 patients may benefit from an HLA-C2-KIR2DL1/S1 graft.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Takuya
authors.initials: T
authors.lastname: Sekine
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: David
authors.initials: D
authors.lastname: Marin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Kai
authors.initials: K
authors.lastname: Cao
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Pramod
authors.initials: P
authors.lastname: Mehta
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Hila
authors.initials: H
authors.lastname: Shaim
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Catherine
authors.initials: C
authors.lastname: Sobieski
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Roy
authors.initials: R
authors.lastname: Jones
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Betul
authors.initials: B
authors.lastname: Oran
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Chitra
authors.initials: C
authors.lastname: Hosing
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Abdullah
authors.initials: A
authors.lastname: Alsuliman
authors.affiliation: The Center for Human Immunobiology, Baylor College of Medicine, Houston, TX; and.
authors.forename: Silke
authors.initials: S
authors.lastname: Paust
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Borje
authors.initials: B
authors.lastname: Andersson
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Uday
authors.initials: U
authors.lastname: Popat
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Muharrem
authors.initials: M
authors.lastname: Muftuoglu
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Rafet
authors.initials: R
authors.lastname: Basar
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Kayo
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Yago
authors.initials: Y
authors.lastname: Nieto
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Nina
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Amanda
authors.initials: A
authors.lastname: Olson
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Amin
authors.initials: A
authors.lastname: Alousi
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Enli
authors.initials: E
authors.lastname: Liu
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Anushruti
authors.initials: A
authors.lastname: Sarvaria
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Simrit
authors.initials: S
authors.lastname: Parmar
authors.affiliation: Imperial College, London, United Kingdom.
authors.forename: Darius
authors.initials: D
authors.lastname: Armstrong-James
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Imahashi
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Molldrem
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX;
authors.forename: Katayoun
authors.initials: K
authors.lastname: Rezvani
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D036101:Cord Blood Stem Cell Transplantation; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006680:HLA Antigens / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics*; D015996:Survival Rate; D061349:Unrelated Donors
chemical_list: D006680:HLA Antigens; D054340:Receptors, KIR