| Institution: | 1. Department of Immunogenetics, Institute of Hematology and Transfusion Medicine, Warsaw, Poland;2. Department of Clinical Immunology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland;3. Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroc?aw, Poland;4. Department of Hematopoietic Stem Cell Transplantation, Institute of Hematology and Transfusion Medicine, Warsaw, Poland;5. Department of Hematology, Blood Malignancies and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland;6. Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch, Gliwice, Poland;7. Department of Oncology Hematology and Paediatric Transplantology, Poznan University of Medical Sciences, Poznan, Poland;8. Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland;9. Department of Hematology and Transplantology, Gdansk Medical University Clinical Center, Gdansk, Poland;10. Department of Hematology, Oncology and Internal Medicine, Warsaw Medical University, Warsaw, Poland;11. Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland;12. Department of Pediatric Hematology Oncology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland;13. Department of Pediatric Hematology and Oncology, Collegium Medicum Nicolaus Copernicus University Hospital, Bydgoszcz, Poland;14. Department of Paediatric Hematology, Oncology and Transplantology, Medical University, Lublin, Poland;15. Department of Transplantation Children’s University Hospital, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland;p. Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland |
| Abstract: | Serious risks in unrelated hematopoietic stem cell transplantation (HSCT) including graft versus host disease (GvHD) and mortality are associated with HLA disparity between donor and recipient. The increased risks might be dependent on disparity in not-routinely-tested multiple polymorphisms in genetically dense MHC region, being organized in combinations of two extended MHC haplotypes (Ehp). We assessed the clinical role of donor-recipient Ehp disparity levels in N?=?889 patients by the population-based detection of HLA allele phase mismatch. We found increased GvHD incidences and mortality rates with increasing Ehp mismatch level even with the same HLA mismatch level. In multivariate analysis HLA mismatch levels were excluded from models and Ehp disparity level remained independent prognostic factor for high grade acute GvHD (p?=?0.000037, HR?=?10.68, 95%CI 5.50–32.5) and extended chronic GvHD (p?<?0.000001, HR?=?15.51, CI95% 5.36–44.8). In group with single HLA mismatch, patients with double Ehp disparity had worse 5-year overall survival (45% vs. 56%, p?=?0.00065, HR?=?4.05, CI95% 1.69–9.71) and non-relapse mortality (40% vs. 31%, p?=?0.00037, HR?=?5.63, CI95% 2.04–15.5) than patients with single Ehp disparity. We conclude that Ehp-linked factors contribute to the high morbidity and mortality in recipients given HLA-mismatched unrelated transplant and Ehp matching should be considered in clinical HSCT. |
