External validation of models for KIR2DS1/KIR3DL1-informed selection of hematopoietic cell donors fails
| Autor: | Schetelig, J., Baldauf, H., Heidenreich, F., Massalski, C., Frank, S., Sauter, J., Stelljes, M., Ayuk, F.A., Bethge, W.A., Bug, G., Klein, S., Wendler, S., Lange, V., Wreede, L.C. de, Furst, D., Kobbe, G., Ottinger, H.D., Beelen, D.W., Mytilineos, J., Fleischhauer, K., Schmidt, A.H., Bomhauser, M., German Cooperative Transp, Deutsch Register Stammzelltransp |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Oncology medicine.medical_specialty Genotype Immunobiology and Immunotherapy medicine.medical_treatment Immunology Medizin Graft vs Host Disease Human leukocyte antigen Hematopoietic stem cell transplantation Biochemistry Donor Selection Young Adult Receptors KIR Internal medicine medicine Humans Transplantation Homologous Cumulative incidence Aged Proportional Hazards Models Retrospective Studies Donor selection Proportional hazards model business.industry Hazard ratio Hematopoietic Stem Cell Transplantation Receptors KIR3DL1 Cell Biology Hematology Middle Aged Transplantation Leukemia Myeloid Acute Myelodysplastic Syndromes Female Unrelated Donors business KIR3DL1 |
| Zdroj: | Blood, 135(16), 1386-1395. AMER SOC HEMATOLOGY |
| DOI: | 10.1182/blood.2019002887 |
| Popis: | Several studies suggest that harnessing natural killer (NK) cell reactivity mediated through killer cell immunoglobulin-like receptors (KIRs) could reduce the risk of relapse after allogeneic hematopoietic cell transplantation. Based on one promising model, information on KIR2DS1 and KIR3DL1 and their cognate ligands can be used to classify donors as KIR-advantageous or KIR-disadvantageous. This study was aimed at externally validating this model in unrelated donor hematopoietic cell transplantation. The impact of the predictor on overall survival (OS) and relapse incidence was tested in a Cox regression model adjusted for patient age, a modified disease risk index, Karnofsky performance status, donor age, HLA match, sex match, cytomegalovirus match, conditioning intensity, type of T-cell depletion, and graft type. Data from 2222 patients with acute myeloid leukemia or myelodysplastic syndrome were analyzed. KIR genes were typed by using high-resolution amplicon-based next-generation sequencing. In univariable analyses and subgroup analyses, OS and the cumulative incidence of relapse of patients with a KIR-advantageous donor were comparable to patients with a KIR-disadvantageous donor. The adjusted hazard ratio from the multivariable Cox regression model was 0.99 (Wald test, P = .93) for OS and 1.04 (Wald test, P = .78) for relapse incidence. We also tested the impact of activating donor KIR2DS1 and inhibition by KIR3DL1 separately but found no significant impact on OS and the risk of relapse. Thus, our study shows that the proposed model does not universally predict NK-mediated disease control. Deeper knowledge of NK-mediated alloreactivity is necessary to predict its contribution to graft-versus-leukemia reactions and to eventually use KIR genotype information for donor selection. |
| Databáze: | OpenAIRE |
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