Quantifying HLA Mismatches at Epitope Level in Haplo-HSCT: Impact in the Outcome in Strategies Using PTCy.

Autor:	Gil-Etayo FJ; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., Niño-Ramírez JE; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., Fonseca-Santos M; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., Arroyo-Sánchez D; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., Navarro-Bailón A; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., Vicente Parra A; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., Jiménez Hernaz I; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., Terradillos Sánchez P; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain., Boix F; Transfusion Centre of Comunidad Valenciana, Valencia, Spain., Alcoceba M; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., Marín L; Immunology Unit, Clinical Analysis Department, Albacete University Hospital Complex, Albacete, Spain., Pérez-López E; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., Cabrero M; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., Martín-López AÁ; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., López M; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., Baile M; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., Avendaño A; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., Cabero A; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., García-Bacelar A; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain., Vázquez L; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain.; Faculty of Medicine, University of Salamanca (USAL), Salamanca, Spain., Sánchez-Guijo F; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain.; Faculty of Medicine, University of Salamanca (USAL), Salamanca, Spain., García-Sanz R; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain.; Faculty of Medicine, University of Salamanca (USAL), Salamanca, Spain., López-Corral L; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain.; Faculty of Medicine, University of Salamanca (USAL), Salamanca, Spain., Tejeda Velarde A; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.; Centro de Investigación Contra el Cáncer (CIC), Salamanca, Spain.
Jazyk:	angličtina
Zdroj:	HLA [HLA] 2024 Nov; Vol. 104 (5), pp. e15738.
DOI:	10.1111/tan.15738
Abstrakt:	Haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is one of the most effective therapies for treating malignant haematological disorders. However, HLA disparities are significant barriers to the success of this process since they increase the risk of graft versus host disease (GvHD). HLA disparities quantification could help to anticipate the probability and degree of GvHD, but the best tool for such quantification remains a challenge. The aim of this study was to quantify the degree of HLA epitope incompatibilities using PIRCHE (Predicted Indirectly Recognisable HLA Epitopes) algorithm for immunogenicity prediction and their potential relationship with GvHD degree and clinical outcome. We studied 145 patients who underwent a haplo-HSCT with post-transplant cyclophosphamide (PTCy) from a related donor between 2013 and 2020 at our centre evaluating molecular HLA mismatches by PIRCHE-algorithm. Patients with PIRCHE Score (PS) I + II > 38 in GvH direction, developed acute GvHD grade II-IV earlier than their counterparts (HR: 1.71, 95% CI: 1.02-2.87, p = 0.032). In addition, PS-B > 1 in GvH direction was an independent risk factor for chronic GvHD, (HR: 2.51, 95% CI 1.17-5.36, p = 0.017). A higher incidence of relapse was found for patients with PS-II > 28 HvG (HR: 9.16, 95% CI: 2.47-33.92, p < 0.001) which also favoured a worse GvHD/relapse-free survival in patients with PS-II > 27 in HvG direction (HR: 1.88, 95% CI: 1.11-3.18, p = 0.017). These findings indicate that the alloreactivity inferred by epitope HLA disparities is associated with post-transplant outcomes. Thus, analysing PS could benefit the selection of the most suitable donors allowing patient stratification based on HLA mismatches in the context of haplo-HSCT with PTCy. (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze:	MEDLINE
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