1. Effect of early post-hematopoietic stem cell transplant tacrolimus concentration on transplant outcomes in pediatric recipients: One facility's ten-year experience of immunosuppression with tacrolimus.
- Author
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Braidotti S, Curci D, Maestro A, Zanon D, Maximova N, and Di Paolo A
- Subjects
- Humans, Child, Female, Male, Retrospective Studies, Child, Preschool, Adolescent, Infant, Treatment Outcome, Transplantation, Homologous, Italy, Tacrolimus therapeutic use, Tacrolimus pharmacokinetics, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease drug therapy, Graft vs Host Disease prevention & control, Immunosuppressive Agents therapeutic use, Immunosuppressive Agents pharmacokinetics
- Abstract
Acute graft-versus-host disease (GVHD) is a common life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), ranking as the second leading cause of death among recipients, surpassed only by disease relapse. Tacrolimus is commonly used for GVHD prophylaxis, but achieving therapeutic blood levels is challenging, particularly in pediatrics, due to the narrow therapeutic window and the high interindividual variability. The retrospective study conducted at IRCCS "Burlo Garofolo" in Italy aimed to assess the impact of early post-HSCT tacrolimus levels on transplant-related outcomes in pediatric recipients. The population pharmacokinetic model (POP/PK) was set up to describe tacrolimus pharmacokinetics. Elevated tacrolimus (>12-15 ng/ml) levels within the initial weeks post-HSCT are associated with reduced post-transplant infections (p < 0.0001) and decreased incidence of early transplant-related events (p < 0.01), including a lower incidence of acute GVHD (p < 0.05 on day 0). High tacrolimus exposure can lead to an increased risk of chronic GVHD (p < 0.0001) and reduced overall survival (p < 0.01). Personalized dosing and therapeutic monitoring of tacrolimus are crucial to ensure optimal outcomes. POP/PK could help achieve this goal, giving us a model by which we can balance immunosuppression while looking at the patient's general well-being and providing the necessary treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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