Pharmacogenetic evaluation for immunoprophylaxis with tacrolimus and cyclosporine in patients undergoing allogeneic hematopoietic stem cell transplantation

• Grant number: 24/07284-9
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2025
• End date: July 31, 2027
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Paulo Caleb Júnior de Lima Santos
• Grantee: Paulo Caleb Júnior de Lima Santos
• Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: João Bosco Pesquero ; Marília Berlofa Visacri ; Patricia Moriel

Abstract

Pharmacogenetic Evaluation for Calcineurin Inhibitor Immune Prophylaxis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation, São Paulo, 2025.Introduction: In 2023, nearly 1,694 allogeneic transplants were performed in Brazil. There are several complications related to allogeneic transplantation, especially graft-versus-host disease (GVHD), which can significantly impact patient morbidity and mortality. Calcineurin inhibitors, such as cyclosporine and tacrolimus, are drugs indicated for immune prophylaxis. However, effective and continuous pharmacological monitoring are necessary due to the risks of toxicities and for the effectiveness of immunosuppression. In the pharmacogenetic scenario in the Brazilian population, there is interindividual variability associated with polymorphisms in genes related to the transport and biotransformation of these drugs, in addition to being an innovative study regarding allogeneic transplantation. Objective: To evaluate the effect of genetic polymorphisms on clinical outcomes in immune prophylaxis with calcineurin inhibitor in patients undergoing allogeneic hematopoietic stem cell transplantation. Methodology: Patients undergoing allogeneic transplantation will be included, 940 patients from INCA and 501 patients from GRAACC. Polymorphisms will be identified by Microarray (Infinium Global Diversity Array with Enhanced PGx - GDA PGx). General and clinical data, plasma concentrations of drugs, incidence of primary rejection, toxicities classified according to CTCAE (grades I to IV), and acute GVHD (grades I to IV) will be collected. Expected results: Innovative data in pharmacogenetic due to the representative sample size of Brazilian patients. (AU)