title: Prediction of NK Cell Licensing Level in Selection of Hematopoietic Stem Cell Donor, Initial Results.
abstract: Natural killer (NK) cell licensing status depends on clonal expression of inhibitory killer cell immunoglobulin-like receptors (iKIR) and short term HLA environment. Licensed NK cells are more efficient in tumor killing than unlicensed NK cells. Cognate KIR-HLA pairs in hematopoietic stem cell transplant (HSCT) donor and recipient are decisive for the possible change in the NK cell licensing status after HSCT. We assessed clinical outcomes in 297 patients with lymphoproliferative or myeloproliferative malignancies, or myelodysplastic syndrome in a model with upward licensing, downward resetting, and unchanged licensing genetics status after T cell replate HSCT from unrelated donors. We found extremely low (0%) relapse/progression incidence (RI), and better (59%) event-free survival (EFS) in recipients with upward licensing status and highly increased RI (37.5%), and reduced EFS (8%) among patients with the downward resetting status of repopulated donor NK cells after HSCT, as compared with unchanged NK cell licensing (RI 23%, EFS 47%). These trends were confirmed in adjusted multivariable models (for RI p = 6.66E-09, OR = 1.47, 95% CI 1.29-1.66 and for EFS p = 3.79E-13, OR = 1.67, 95% CI 1.50-1.84). Differences in the incidence of acute graft versus host disease (GvHD 62, 69, and 47%) and chronic GvHD (24, 44, and 15%, respectively) in three groups were insignificant. It would be rationale the preferential selection of the donors with upward licensing over downward resetting inhibitory KIR:HLA constellation and inclusion of the KIR genotyping in the donor selection algorithm for malignant patients. Further studies using enlarged cohorts of patients with more homogenous diagnosis are essential to reliably verify these preliminary data.
authors.affiliation: Institute of Hematology and Transfusion Medicine, Indira Gandhi 14, 02-776, Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Rogatko-Koroś
authors.affiliation: Institute of Hematology and Transfusion Medicine, Indira Gandhi 14, 02-776, Warsaw, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Mika-Witkowska
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wrocław, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bogunia-Kubik
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wrocław, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wysoczańska
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wrocław, Poland.|Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wrocław, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Jaskuła
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wrocław, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kościńska
authors.affiliation: Institute of Hematology and Transfusion Medicine, Indira Gandhi 14, 02-776, Warsaw, Poland.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Nestorowicz
authors.affiliation: Institute of Hematology and Transfusion Medicine, Indira Gandhi 14, 02-776, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Dziopa
authors.affiliation: Institute of Hematology and Transfusion Medicine, Indira Gandhi 14, 02-776, Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Szlendak
authors.affiliation: Institute of Hematology and Transfusion Medicine, Indira Gandhi 14, 02-776, Warsaw, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Gwozdowicz
authors.affiliation: Institute of Hematology and Transfusion Medicine, Indira Gandhi 14, 02-776, Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Graczyk-Pol
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wrocław, Poland.|Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wrocław, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lange
authors.affiliation: Institute of Hematology and Transfusion Medicine, Indira Gandhi 14, 02-776, Warsaw, Poland. jnowak@ihit.waw.pl.
authors.forename: Jacek
authors.identifier: http://orcid.org/0000-0002-3474-7597
authors.initials: J
authors.lastname: Nowak
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000483:Alleles; D001853:Bone Marrow; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D046148:Donor Selection; D005838:Genotype; D006086:Graft vs Host Disease; D006680:HLA Antigens / Q000737:chemistry*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology*; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000628:therapy; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000628:therapy; D009196:Myeloproliferative Disorders / Q000276:immunology / Q000628:therapy; D054340:Receptors, KIR / Q000235:genetics / Q000276:immunology*; D012008:Recurrence; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D054340:Receptors, KIR
keywords: Bone marrow donor selection; Hematopoietic malignancy; Hematopoietic stem cell transplantation; NK cell licensing; Relapse; Unrelated donors