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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1396284
Identification of predictive models including polymorphisms in cytokines genes and clinical variables associated with post-transplant complications after identical HLAallogeneic stem cell transplantation
Provisionally accepted
Paula Muñiz Sevilla
1,2
María Martínez
3
Rebeca Bailén
1,2
Maria Chicano
1,2
Gillen Oarbeascoa
1,2
Juan Carlos Trivino
4
Ismael de la Iglesia
1,2
Sara Fernández De Córdoba
1,2
Javier Anguita
1,2
Mi Kwon
1,2
Jose Luis Díez-Martín
1,2
Pablo Olmos
3
Carolina M. Laperche
1,2*
Ismael Buño
1,2*- 1 Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Madrid, Spain
- 2 Department of Hematology, Gregorio Marañón Hospital, Madrid, Madrid, Spain
- 3 Universidad Carlos III de Madrid, Getafe, Madrid, Spain
- 4 Sistemas Genómicos, Paterna, Spain
Backgrounds: Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies, it can be associated with relevant post-transplant complications. Several reports have shown that polymorphisms in immune system genes are correlated with the development of post-transplant complications. Within this context, this work focuses on identifying novel polymorphisms in cytokine genes and developing predictive models to anticipate the risk of developing GVHD, transplant-related mortality (TRM), relapse and overall survival (OS). Methods: Our group developed a 132-cytokine gene panel which was tested in 90 patients who underwent an HLA-identical sibling-donor allo-HSCT. Bayesian logistic regression (BLR) models were used to select the most relevant variables. Based on the cut-off points selected for each model, patients were classified as being at high or low-risk for each of the posttransplant complications (aGVHD II-IV, aGVHD III-IV, cGVHD, mod-sev cGVHD, TRM, relapse and OS)-Results: A total of 737 polymorphisms were selected from the custom panel genes. Of these, 41 polymorphisms were included in the predictive models in 30 cytokine genes were selected (17 interleukins and 13 chemokines). Of these polymorphisms, 5 (12.2%) were located in coding regions, and 36 (87.8%) in non-coding regions. All models had a statistical significance of p<0.0001.Conclusions: Overall, genomic polymorphisms in cytokine genes make it possible to anticipate the development all complications studied following allo-HSCT and, consequently, to optimize the clinical management of patients.
Keywords: polymorphisms, graft-versus-host-disease, predictive models, Cytokines, Allogeneic transplantation
Received: 05 Mar 2024; Accepted: 08 Jul 2024.
Copyright: © 2024 Muñiz Sevilla, Martínez, Bailén, Chicano, Oarbeascoa, Trivino, de la Iglesia, Fernández De Córdoba, Anguita, Kwon, Díez-Martín, Olmos, Laperche and Buño. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Carolina M. Laperche, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Madrid, Spain
Ismael Buño, Department of Hematology, Gregorio Marañón Hospital, Madrid, 28007, Madrid, Spain
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