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Impact of Early Intrapatient Variability of Tacrolimus_Pharmaceuticals.pdf (1.13 MB)

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2022-12-09

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cc by (c) Marco, Daniel N. et al, 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/198384

Impact of Early Intrapatient Variability of Tacrolimus Concentrations on the Risk of Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation Using High-Dose Post-Transplant Cyclophosphamide

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https://doi.org/10.3390/ph15121529

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Tacrolimus (Tac) is a pivotal immunosuppressant agent used to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloHSCT). Tac is characterized by a narrow therapeutic window and a high inter-patient and intra-patient pharmacokinetic variability (IPV). Although high IPV of Tac concentrations has been associated with adverse post-transplant outcomes following solid organ transplantation, the effects of Tac IPV on alloHSCT recipients have not been determined. Tac IPV was therefore retrospectively evaluated in 128 alloHSCT recipients receiving high-dose post-transplant cyclophosphamide (PTCy) and the effects of Tac IPV on the occurrence of acute GVHD (aGVHD) were analyzed. Tac IPV was calculated from pre-dose concentrations (C0) measured during the first month after Tac initiation. The cumulative rates of grades II-IV and grades III-IV aGVHD at day +100 were 22.7% and 7%, respectively. Higher Tac IPV was associated with a greater risk of developing GVHD, with patients having IPV > 50th percentile having significantly higher rates of grades II-IV (34.9% vs. 10.8%; hazard ratio [HR] 3.858, p < 0.001) and grades III-IV (12.7% vs. 1.5%; HR 9.69, p = 0.033) aGVHD than patients having IPV ? 50th percentile. Similarly, patients with IPV > 75th percentile had higher rates of grades II-IV (41.9% vs. 16.5%; HR 3.30, p < 0.001) and grades III-IV (16.1% vs. 4.1%; HR 4.99, p = 0.012) aGVHD than patients with IPV ? 75th percentile. Multivariate analyses showed that high Tac IPV (>50th percentile) was an independent risk factor for grades II-IV (HR 2.99, p = 0.018) and grades III-IV (HR 9.12, p = 0.047) aGVHD. Determination of Tac IPV soon after alloHSCT could be useful in identifying patients at greater risk of aGVHD.

Matèries

Trasplantament d'òrgans, Cèl·lules mare

Matèries (anglès)

Transplantation of organs, Stem cells

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Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

MARCO, Daniel n., Salas. Maria Queralt, GUTIÉRREZ GARCÍA, Gonzalo, MONGE ESCARTÍN, Inés, RIU, Gisela, CARCELERO, Esther, ROMA, Joan ramon, LLOBET, Noemí, ARCARONS, Jordi, SUÁREZ-LLEDÓ GRANDE, María, MARTÍNEZ, Nuria, PEDRAZA NAVARRETE, Alexandra, DOMENECH, Ariadna, ROSIÑOL DACHS, Laura, FERNÁNDEZ AVILÉS, Francesc, URBANO ISPIZUA, Álvaro, ROVIRA, Montserrat, BRUNET I SERRA, Mercè, MARTÍNEZ, Carmen. Impact of Early Intrapatient Variability of Tacrolimus Concentrations on the Risk of Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation Using High-Dose Post-Transplant Cyclophosphamide. _Pharmaceuticals_. 2022. Vol. 15, núm. 12. [consulta: 17 de febrer de 2026]. ISSN: 1424-8247. [Disponible a: https://hdl.handle.net/2445/198384]

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