Donor KIR genotype based outcome prediction after allogeneic stem cell transplantation: no land in sight
Frontiers in Immunology, vol. 15, pp. 1350470
Abstract
Optimizing natural killer (NK) cell alloreactivity could further improve outcome after allogeneic hematopoietic cell transplantation (alloHCT). The donor’s Killer-cell Immunoglobulin-like Receptor (KIR) genotype may provide important information in this regard. In the past decade, different models have been proposed aiming at maximizing NK cell activation by activating KIR-ligand interactions or minimizing inhibitory KIR-ligand interactions. Alternative classifications intended predicting outcome after alloHCT by donor KIR-haplotypes. In the present study, we aimed at validating proposed models and exploring more classification approaches. To this end, we analyzed samples stored at the Collaborative Biobank from HLA-compatible unrelated stem cell donors who had donated for patients with acute myeloid leukemia (AML) or myelodysplastic neoplasm (MDS) and whose outcome data had been reported to EBMT or CIBMTR. The donor KIR genotype was determined by high resolution amplicon-based next generation sequencing. We analyzed data from 5,017 transplants. The median patient age at alloHCT was 56 years. Patients were transplanted for AML between 2013 and 2018. Donor-recipient pairs were matched for HLA-A, -B, -C, -DRB1, and -DQB1 (79%) or had single HLA mismatches. Myeloablative conditioning was given to 56% of patients. Fifty-two percent of patients received anti-thymocyte-globulin-based graft-versus-host disease prophylaxis, 32% calcineurin-inhibitor-based prophylaxis, and 7% post-transplant cyclophosphamide-based prophylaxis. We tested several previously reported classifications in multivariable regression analyses but could not confirm outcome associations. Exploratory analyses in 1,939 patients (39%) who were transplanted from donors with homozygous centromeric (cen) or telomeric (tel) A or B motifs, showed that the donor cen B/B -tel A/A diplotype was associated with a trend to better event-free survival (HR 0.84, p=.08) and reduced risk of non-relapse mortality (NRM) (HR 0.65, p=.01). When we further dissected the contribution of B subtypes, we found that only the cen B01/B01 - telA/A diplotype was associated with a reduced risk of relapse (HR 0.40, p=.04) while all subtype combinations contributed to a reduced risk of NRM. This exploratory finding has to be validated in an independent data set. In summary, the existing body of evidence is not (yet) consistent enough to recommend use of donor KIR genotype information for donor selection in routine clinical practice.
Authors 29
-
Johannes Schetelig corresponding
Deutsche Knochenmarkspenderdatei · Technische Universität Dresden
Affiliation as printed
Clinical Trials Unit, DKMS Group, Dresden, Germany
Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany
-
Deutsche Knochenmarkspenderdatei
Affiliation as printed
Clinical Trials Unit, DKMS Group, Dresden, Germany
-
Deutsche Knochenmarkspenderdatei · Technische Universität Dresden
Affiliation as printed
Clinical Trials Unit, DKMS Group, Dresden, Germany
Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany
-
European Society for Blood and Marrow Transplantation
Affiliation as printed
EBMT Leiden Study Unit, Leiden, Netherlands
-
Affiliation as printed
Center for International Blood and Marrow Transplant Research, National Marrow Donor Program (NMDP), Minneapolis, MN, United States
-
Affiliation as printed
RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia
-
Affiliation as printed
Klinik für Hämatologie und Stammzelltransplantation, Universitätsklinikum Essen, Essen, Germany
-
Copenhagen University Hospital · Rigshospitalet
Affiliation as printed
Bone Marrow Transplant Unit, Department of Hematology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark
-
Affiliation as printed
Department of Medicine V, University of Heidelberg, Heidelberg, Germany
-
Centre Hospitalier Universitaire de Bordeaux
Affiliation as printed
Service Hématologie clinique de Thérapie cellulaire, Centre Hospitalier Universitaire Bordeaux, Université de Bordeaus, Bordeaux, France
-
Institute of Haematology and Blood Transfusion
Affiliation as printed
Transplant Unit and Intensive Care Unit, Institute of Hematology and Bood Transfusion, Prague, Czechia
-
University Medical Center of the Johannes Gutenberg University Mainz
Affiliation as printed
Center for Cellular Immunotherapy and Stem Cell Transplantation, Third Medical Department, Hematology and Oncology, University Cancer Center Mainz, Mainz, Germany
-
University Medical Center Groningen · University of Groningen
Affiliation as printed
University Medical Center Groningen, University of Groningen, Groningen, Netherlands
-
Affiliation as printed
Department of Haematology & Stem Cell Transplantation, Birmingham Heartlands Hospital, Birmingham, United Kingdom
-
Instituto Português de Oncologia Francisco Gentil
Affiliation as printed
Department of Hematology, Instituto Português de Oncologia de Lisboa, Lisboa, Portugal
-
Affiliation as printed
Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, Romania
-
Leiden University Medical Center
Affiliation as printed
Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
-
Affiliation as printed
DKMS Life Science Lab, Dresden, Germany
-
Deutsche Knochenmarkspenderdatei
Affiliation as printed
DKMS Group, Tübingen, Germany
DKMS Life Science Lab, Dresden, Germany
-
Deutsche Knochenmarkspenderdatei
Affiliation as printed
DKMS Group, Tübingen, Germany
-
NewYork–Presbyterian Hospital · Weill Cornell Medicine
Affiliation as printed
Department of Hematology & Medical Oncology, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, United States
-
Affiliation as printed
Center for International Blood and Marrow Transplant Research, National Marrow Donor Program (NMDP), Minneapolis, MN, United States
-
Affiliation as printed
Center for International Blood and Marrow Transplant Research, National Marrow Donor Program (NMDP), Minneapolis, MN, United States
-
Anthony Nolan · The Royal Free Hospital · University College London
Affiliation as printed
Anthony Nolan Research Institute, Royal Free Hospital, London & Cancer Institute, University College London, London, United Kingdom
-
National Cancer Institute · Division of Cancer Epidemiology and Genetics
Affiliation as printed
National Cancer Institute, Division of Cancer Epidemiology & Genetics, Bethesda, MD, United States
-
Medical University of South Carolina
Affiliation as printed
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, United States
-
Affiliation as printed
Haematology and BMT, Ospedale San Raffaele s.r.l., Milan, Italy
-
Affiliation as printed
Institut Paoli-Calmettes, Centre de Lutte Contre le Cancer, Marseille, France
-
Affiliation as printed
Institute for Experimental Cellular Therapy, University Hospital, Essen, Germany
Cited by 14 stored of 14
14 results
No patents citing this paper on Lens.org (checked 2026-10-11).