LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
Por:
Cruz D., Rodríguez-Romanos R., González-Bartulos M., García-Cadenas I., de la Cámara R., Heras I., Buño I., Santos N., Lloveras N., Velarde P., Tuset E., Martínez C., González M., Sanz G.F., Ferrá C., Sampol A., Coll R., Pérez-Simón J.A., López-Jiménez J., Jurado M., Gallardo D.
Publicada:
1 ene 2023
Ahead of Print:
20 ene 2023
Resumen:
Introduction: The association of polymorphisms in molecules involved in the immune response (checkpoint inhibitors) with the clinical outcome after allogeneic transplantation (alloHSCT) has been described. Lymphocyte Activation 3 (LAG3) is a surface protein that plays a regulatory role in immunity as an inhibitory immune checkpoint molecule. Methods: To determine its role in the alloHSCT setting, we analyzed 797 patients transplanted from HLA-identical sibling donors. The LAG3 rs870849 C>T polymorphism was genotyped in donors. Results: We detected a higher incidence of severe acute GVHD in patients transplanted from donors with TT genotype (p: 0.047, HR 1.64; 95% CI 1.01 – 2.67). Overall survival (OS) was worse for patients transplanted from donors with the rs870849 CT/TT genotype (0.020; HR, 1.44; 95% CI 1.06 – 1.96), as well as disease-free survival (DFS) (p: 0.002; HR 1.58, 95%CI: 1.18 – 2.14) and transplant-related mortality (TRM) (p< 0.001; HR: 1.88, 95% CI 1.29 – 2.74). When combining the LAG3 rs870849 and the PDCD1 rs36084323 genotypes of the donor, three genetic groups were well defined, allowing a good stratification of the risk of acute GVHD, TRM, OS and DFS. Discussion: We conclude that the LAG3 genotype of the donor may be considered in donors’ selection. As this selection may be limited in the HLA-identical sibling donor scenario, further studies exploring the impact of LAG3 genotype of the donor in unrelated transplantation are warranted. Copyright © 2023 Cruz, Rodríguez-Romanos, González-Bartulos, García-Cadenas, de la Cámara, Heras, Buño, Santos, Lloveras, Velarde, Tuset, Martínez, González, Sanz, Ferrá, Sampol, Coll, Pérez-Simón, López-Jiménez, Jurado and Gallardo.
Filiaciones:
Cruz D.:
Hematology Department, Institut Català d’Oncologia - Hospital Dr. Josep Trueta, Institut d’Investigació Biomèdica de Girona (IDIBGI), Josep Carreras Research Institute, Girona, Spain
Rodríguez-Romanos R.:
Hematology Department, Institut Català d’Oncologia - Hospital Dr. Josep Trueta, Institut d’Investigació Biomèdica de Girona (IDIBGI), Josep Carreras Research Institute, Girona, Spain
González-Bartulos M.:
Hematology Department, Institut Català d’Oncologia - Hospital Dr. Josep Trueta, Institut d’Investigació Biomèdica de Girona (IDIBGI), Josep Carreras Research Institute, Girona, Spain
García-Cadenas I.:
Hematology Department, Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain
de la Cámara R.:
Hematology Department, Hospital La Princesa, Madrid, Spain
Heras I.:
Hematology Department, Hospital General Universitario Morales Meseguer, Murcia, Spain
Buño I.:
Hematology Department and Genomics Unit, Hospital General Universitario Gregorio Marañón, Gregorio Marañón Health Research Institute (IiSGM), Complutense University, Madrid, Spain
Santos N.:
Hematology Department, Institut Català d’Oncologia - Hospital Dr. Josep Trueta, Institut d’Investigació Biomèdica de Girona (IDIBGI), Josep Carreras Research Institute, Girona, Spain
Lloveras N.:
Hematology Department, Institut Català d’Oncologia - Hospital Dr. Josep Trueta, Institut d’Investigació Biomèdica de Girona (IDIBGI), Josep Carreras Research Institute, Girona, Spain
Department of Medicine, Universitat de Girona, Girona, Spain
Velarde P.:
Hematology Department, Institut Català d’Oncologia - Hospital Dr. Josep Trueta, Institut d’Investigació Biomèdica de Girona (IDIBGI), Josep Carreras Research Institute, Girona, Spain
Tuset E.:
Hematology Department, Institut Català d’Oncologia - Hospital Dr. Josep Trueta, Institut d’Investigació Biomèdica de Girona (IDIBGI), Josep Carreras Research Institute, Girona, Spain
Martínez C.:
Hematology Department, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
González M.:
Hematology Department, Hospital Clínico Universitario, Salamanca, Spain
Sanz G.F.:
Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
Ferrá C.:
Hematology Department, Institut Català d’Oncologia – Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Badalona, Spain
Sampol A.:
Hematology Department, Hospital Universitari Son Espases, IdISBa, Palma de Mallorca, Spain
Coll R.:
Hematology Department, Institut Català d’Oncologia - Hospital Dr. Josep Trueta, Institut d’Investigació Biomèdica de Girona (IDIBGI), Josep Carreras Research Institute, Girona, Spain
Department of Medicine, Universitat de Girona, Girona, Spain
Pérez-Simón J.A.:
Hematology Department, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, Universidad de Sevilla, Sevilla, Spain
López-Jiménez J.:
Hematology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
Jurado M.:
Hematology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain
Gallardo D.:
Hematology Department, Institut Català d’Oncologia - Hospital Dr. Josep Trueta, Institut d’Investigació Biomèdica de Girona (IDIBGI), Josep Carreras Research Institute, Girona, Spain
Department of Medicine, Universitat de Girona, Girona, Spain
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