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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

Resum

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, 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: 8 de gener de 2026]. ISSN: 1424-8247. [Disponible a: https://hdl.handle.net/2445/198384]

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