Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation.
Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a highly polymorphic ligand of the activating NKG2D receptor on natural killer (NK) cells, γδ-T cells, and NKT cells. MICA incompatibilities have been associated with an increased graft-versus-host disease (GVHD) incidence, and the MICA-129 (met/val) dimorphism has been shown to influence NKG2D signaling in unrelated hematopoietic stem cell transplantation (uHSCT). We investigated the effect of MICA matching on survival after uHSCT. We sequenced 2172 patients and their respective donors for MICA. All patients and donors were high-resolution HLA-typed and matched for 10/10 (n = 1379), 9/10 (n = 636), or 8/10 (n = 157) HLA alleles. Within each HLA match group, cases matched and mismatched for MICA and MICA-129 were analyzed for the end points overall survival (OS), disease-free survival (DFS), nonrelapse mortality (NRM), relapse-incidence (RI), and GVHD. Mismatches at the MICA locus as well as MICA-129 increased with the number of HLA mismatches (MICA mismatched 10/10, 9.2% [n = 127]; 9/10, 22.3% [n = 142]; 8/10, 38.2% [n = 60]; MICA-129 mismatched 10/10, 3.9% [n = 54]; 9/10, 10.2% [n = 65]; 8/10, 17.2% [n = 27]). Adverse OS was observed in the 10/10 match group if MICA-129 was mismatched (10/10, hazard ratio [HR], 1.77; confidence interval [CI], 1.22-2.57; P = .003). MICA-129 mismatches correlated with a significantly worse outcome for DFS in the 10/10 HLA match group (HR, 1.77; CI, 1.26-2.50; P = .001). Higher rates of aGVHD were seen in MICA-129 mismatched cases. Our results indicate that MICA-129 matching is relevant in uHSCT. Prospective typing of patients and donors in unrelated donor search may identify mismatches for MICA-129, and compatible donor selection may improve outcome for this small but high-risk subgroup.
Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg-Hessen, Ulm, and University Hospital Ulm, Ulm, Germany.|Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
Daniel
D
Fuerst
Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg-Hessen, Ulm, and University Hospital Ulm, Ulm, Germany.|Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
Christine
C
Neuchel
Department of Hematology/Oncology, University of Leipzig, Leipzig, Germany.
Dietger
D
Niederwieser
Department of Internal Medicine III, University of Ulm, Ulm, Germany.
Donald
D
Bunjes
Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, University of Kiel, Kiel, Germany.
Martin
M
Gramatzki
Department of Medicine III, Johannes Gutenberg-University Mainz, Mainz, Germany.
Eva
E
Wagner
Department of Hematology/Oncology, Georg-August-University Göttingen, Göttingen, Germany.
Gerald
G
Wulf
Department of Hematology/Oncology, Asklepios Klinik St. Georg Hamburg, Hamburg, Germany.
Bertram
B
Glass
Department Internal Medicine I, Universitätsklinikum des Saarlandes, Homburg, Germany.
Michael
M
Pfreundschuh
Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Hermann
H
Einsele
Hematology/Oncology Department, Charité Campus Virchow Berlin, Berlin, Germany.
Renate
R
Arnold
Centre for Bone Marrow and Blood Stem Cell Transplantation, Deutsche Klinik für Diagnostik, Wiesbaden, Germany.
Gernot
G
Stuhler
Medical Clinic 5: Hematology, Oncology, Nuremberg Hospital, Nuremberg, Germany.
Kerstin
K
Schaefer-Eckart
Department of Medicine III, Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.
Sebastian
S
Freitag
Division of Hematology and Oncology, Oldenburg Clinic, University of Rostock, Oldenburg, Germany.
Jochen
J
Casper
2nd Department of Internal Medicine, Oncology and Hematology, Robert Bosch Hospital Stuttgart, Stuttgart, Germany.
Martin
M
Kaufmann
Hematology/Oncology, Evangelic Clinic Essen-Werden, Essen-Werden, Germany.
Mohammed
M
Wattad
Hematology/Oncology, Klinikum Bremen-Mitte, Bremen, Germany.
Bernd
B
Hertenstein
Universitätsmedizin Mannheim, Med. Klinik III, Mannheim, Germany.
Stefan
S
Klein
Medizinische Klinik III, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany.
Mark
M
Ringhoffer
Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
Daphne
D
Mytilineos
Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg-Hessen, Ulm, and University Hospital Ulm, Ulm, Germany.|Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
Chrysanthi
C
Tsamadou
Zentrales Knochenmarkspender-Register für Deutschland, German National Bone Marrow Donor Registry, Ulm, Germany; and.|German Registry for Stem Cell Transplantation, Ulm, Germany.
Carlheinz
C
Mueller
Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg-Hessen, Ulm, and University Hospital Ulm, Ulm, Germany.|Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
Hubert
H
Schrezenmeier
Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg-Hessen, Ulm, and University Hospital Ulm, Ulm, Germany.|Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.|German Registry for Stem Cell Transplantation, Ulm, Germany.
Joannis
J
Mytilineos
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D056426:Genetic Loci; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D016019:Survival Analysis; D014019:Tissue Donors; D055815:Young Adult
D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A