Evaluation of Tacrolimus Levels and Risk of Acute Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant

Huynh, David; Freeman, Tracelyn; Marshall, Vincent D.; Markstrom, Denise; Frame, David

doi:10.1016/j.bbmt.2018.12.352

Cited by 3 publications

(5 citation statements)

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“… 25 , 31 , 32 The cutoff or target trough levels varied among different studies, ranging from 7 to 20 ng/ml in children post‐allogeneic bone marrow transplantation. 8 , 10 , 31 , 33 One study demonstrated that every decrease of 1 ng/ml in tacrolimus mean concentrations over weeks 2–3 post‐transplant leads to an ~ 13% increased incidence of aGVHD. 34 On the contrary, certain reports failed in identifying a relationship between the blood concentrations of tacrolimus and the occurrence of aGVHD in children.…”

Section: Discussionmentioning

confidence: 99%

“…Yet, only a few studies in children have evaluated the relationship between the serum trough levels of tacrolimus and the occurrence of aGVHD, and the relationship remains controversial and inconclusive. There were studies suggesting that a higher target tacrolimus level post-transplant was associated with reduced risk of aGVHD (25,32,33). The cutoff or target trough levels varied among different studies, ranging from 7 to 20 ng/ml in children post allogeneic bone marrow transplantation (8,10,32,34).…”

Section: Accepted Articlementioning

confidence: 99%

“…There were studies suggesting that a higher target tacrolimus level post-transplant was associated with reduced risk of aGVHD (25,32,33). The cutoff or target trough levels varied among different studies, ranging from 7 to 20 ng/ml in children post allogeneic bone marrow transplantation (8,10,32,34). One study demonstrated that every decrease of 1 ng/ml in tacrolimus mean concentrations over week 2-3 post-transplant leads to an approximately 13% increased incidence of aGVHD (35).…”

Section: Accepted Articlementioning

confidence: 99%

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Evaluating risk factors for acute graft versus host disease in pediatric hematopoietic stem cell transplant patients receiving tacrolimus

Phan

Chavan

Beuttler

et al. 2021

Clinical Translational Sci

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To identify the clinical and pharmacological risk factors associated with tacrolimus pharmacodynamics for acute GVHD (aGVHD) in pediatric patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related donor. A retrospective cohort Accepted ArticleThis article is protected by copyright. All rights reserved single center chart review study was conducted with pediatric patients who received tacrolimus prophylaxis after allogeneic HSCT between 01/01/2017 and 12/31/2019. Potential risk factors were tested separately between aGVHD and non-aGVHD cohorts and were further analyzed in a logistic regression model with backwards elimination and a partial least squares discriminant analysis. Thirty-three patient cases were included in our study and 52% (17/33) developed aGVHD while on tacrolimus prophylaxis. When tested independently, donor age and sibling versus parent donor/recipient relation were shown statistically significant between aGVHD and non-aGVHD patients (p<0.005). Pharmacological factors associated with tacrolimus treatment failed to demonstrate a significant impact on patient's risk of aGVHD. Using a best fit logistic regression model that tested all the variables together, donor age was the only significant variable predicting patient's risk of aGVHD (p<0.01). Donor relationship and donor age were unable to be evaluated separately and are therefore confounding variables. Among pediatric patients receiving allogeneic HSCT, aGVHD risk is significantly decreased by either sibling donor and/or younger donors. While no conclusions were drawn on the effect of tacrolimus therapy (p=0.08), results warrant additional research with a larger sample size to evaluate the accuracy of monitoring tacrolimus serum trough levels.

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Section: Discussionmentioning

confidence: 99%

Section: Accepted Articlementioning

confidence: 99%

Section: Accepted Articlementioning

confidence: 99%

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Evaluating risk factors for acute graft versus host disease in pediatric hematopoietic stem cell transplant patients receiving tacrolimus

Phan

Chavan

Beuttler

et al. 2021

Clinical Translational Sci

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“…Recent studies which compared the relationship between tacrolimus whole blood concentrations and development of GVHD, showed tacrolimus levels during the first week after transplantation were an independent predictor for the development of acute grades 2–4 GVHD. 12,13…”

Section: Discussionmentioning

confidence: 99%

“…In the same vein, low tacrolimus results from our institution and others have shown low tacrolimus concentrations (<8 ng/ml) during weeks three and four post-transplantation, a time when patients are normally transitioned from IV to PO therapy, are associated with an increased risk for developing acute GVHD ( P < 0.031). 12–14 Thus, use of the 3.1:1 PO:1V conversion ratio could improve chances for achieving tacrolimus target levels and avoiding aGVHD during this critical period. 14–16…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus dose modification in patients receiving concomitant isavuconazole after hematopoietic stem cell transplantation

Trifilio

Rubin

Monacelli

et al. 2020

J Oncol Pharm Pract

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Introduction Isavuconazole is increasingly being used for antifungal prophylaxis during stem cell transplantation. Isavuconazole is a moderate inhibitor of Cytochrome P4503A4, and tacrolimus levels are anticipated to be elevated when given concomitantly with isavuconazole. We developed and validated a dose-modified tacrolimus regimen to better achieve and maintain target tacrolimus levels. Methods: Allogeneic stem cell transplantation recipients who received concomitant tacrolimus and isavuconazole from September 2017 to September 2018 were included. Tacrolimus was adjusted to achieve a target range 8–12 ng/ml. Intravenous tacrolimus was first initiated at 0.02 mg/kg/day on day 1, and transitioned to oral therapy using a 2:1 conversion ratio ( n = 48). Clinical observations showed high interpatient variability. The intravenous dose was then reduced to 0.017 mg/kg/day, and oral:intravenous conversion changed to 3.1:1 ( n = 24). Results Interpatient variability was high (lower in the 0.017 mg/kg/day group; P < 0.0217). Patients in the 0.017 mg/kg/day group required fewer dose changes ( P < 0.023) and had fewer levels >15 ng/ml ( P < 0.021). Median tacrolimus dose declined over time; 0.016, 0.012 and 0.011 on days 1, 7 and 10 for patients receiving 0.02 mg/kg/day and 0.017, 0.014 and 0.013 in the 0.017 mg/kg group. Day 10 tacrolimus accumulation factor was 1.42 Rac(Cmax) in the 0.02 mg/kg/day cohort compared to 1.23 Rac(Cmax) in the 0.017 mg/kg/day cohort ( P < 0.015). When transitioned to oral therapy, a oral:intravenous conversion ratio >3.1:1 was shown to improve chances for achieving target levels ( P > 0.0744). Conclusion We recommend initiating intravenous tacrolimus dose at 0.017 mg/kg/day and using a 3.1:1 oral:intravenous conversion to reduce interpatient variability, drug accumulation and the number of suboptimal tacrolimus levels. Tacrolimus requires frequent drug level monitoring.

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IFNG-AS1 and MAF4 long non-coding RNAs are upregulated in acute leukemia patients who underwent bone marrow transplantation

Jafari

Izadirad

Vatanmakanian

et al. 2021

Current Research in Translational Medicine

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Evaluation of Tacrolimus Levels and Risk of Acute Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant

Cited by 3 publications

References 0 publications

Evaluating risk factors for acute graft versus host disease in pediatric hematopoietic stem cell transplant patients receiving tacrolimus

Evaluating risk factors for acute graft versus host disease in pediatric hematopoietic stem cell transplant patients receiving tacrolimus

Tacrolimus dose modification in patients receiving concomitant isavuconazole after hematopoietic stem cell transplantation

IFNG-AS1 and MAF4 long non-coding RNAs are upregulated in acute leukemia patients who underwent bone marrow transplantation

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