Publication

Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients

Veenhof, H., Koster, R. A., Alffenaar, J-W. C., van den Berg, A. P., de Groot, M. R., Verschuuren, E. A. M., Berger, S. P., Bakker, S. J. L. & Touw, D. J., Dec-2019, In : Clinical chemistry and laboratory medicine. 57, 12, p. 1854-1862 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Veenhof, H., Koster, R. A., Alffenaar, J-W. C., van den Berg, A. P., de Groot, M. R., Verschuuren, E. A. M., Berger, S. P., Bakker, S. J. L., & Touw, D. J. (2019). Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients. Clinical chemistry and laboratory medicine, 57(12), 1854-1862. https://doi.org/10.1515/cclm-2019-0053

Author

Veenhof, Herman ; Koster, Remco A ; Alffenaar, Jan-Willem C ; van den Berg, Aad P ; de Groot, Marco R ; Verschuuren, Erik A M ; Berger, Stefan P ; Bakker, Stephan J L ; Touw, Daan J. / Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients. In: Clinical chemistry and laboratory medicine. 2019 ; Vol. 57, No. 12. pp. 1854-1862.

Harvard

Veenhof, H, Koster, RA, Alffenaar, J-WC, van den Berg, AP, de Groot, MR, Verschuuren, EAM, Berger, SP, Bakker, SJL & Touw, DJ 2019, 'Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients', Clinical chemistry and laboratory medicine, vol. 57, no. 12, pp. 1854-1862. https://doi.org/10.1515/cclm-2019-0053

Standard

Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients. / Veenhof, Herman; Koster, Remco A; Alffenaar, Jan-Willem C; van den Berg, Aad P; de Groot, Marco R; Verschuuren, Erik A M; Berger, Stefan P; Bakker, Stephan J L; Touw, Daan J.

In: Clinical chemistry and laboratory medicine, Vol. 57, No. 12, 12.2019, p. 1854-1862.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Veenhof H, Koster RA, Alffenaar J-WC, van den Berg AP, de Groot MR, Verschuuren EAM et al. Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients. Clinical chemistry and laboratory medicine. 2019 Dec;57(12):1854-1862. https://doi.org/10.1515/cclm-2019-0053


BibTeX

@article{d5435c2ffef640c3b0d1d1a37306bfe0,
title = "Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients",
abstract = "Background: Monitoring of immunosuppressive drugs such as everolimus and sirolimus is important in allograft rejection prevention in transplant patients. Dried blood spots (DBS) sampling gives patients the opportunity to sample a drop of blood from a fingerprick at home, which can be sent to the laboratory by mail.Methods: A total of 39 sirolimus and 44 everolimus paired fingerprick DBS and whole blood (WB) samples were obtained from 60 adult transplant patients for method comparison using Passing-Bablok regression. Bias was assessed using Bland-Altman. Two validation limits were pre-defined: limits of analytical acceptance were set at >67% of all paired samples within 20% of the mean of both samples and limits of clinical relevance were set in a multidisciplinary team at >80% of all paired samples within 15% of the mean of both samples.Results: For both sirolimus and everolimus, Passing-Bablok regression showed no differences between WB and DBS with slopes of 0.86 (95% CI slope, 0.72-1.02) and 0.96 (95% CI 0.84-1.06), respectively. Only everolimus showed a significant constant bias of 4%. For both sirolimus and everolimus, limits of analytical acceptance were met (76.9% and 81.8%, respectively), but limits or clinical relevance were not met (77.3% and 61.5%, respectively).Conclusions: Because pre-defined limits of clinical relevance were not met, this DBS sampling method for sirolimus and everolimus cannot replace WB sampling in our center at this time. However, if the clinical setting is compatible with less strict limits for clinical relevance, this DBS method is suitable for clinical application.",
keywords = "dried blood spots, immunosuppressants, microsampling, validation, CYCLOSPORINE-A, REGRESSION PROCEDURES, TACROLIMUS, VALIDATION, MS/MS, HEMATOCRIT, CREATININE, SAMPLES",
author = "Herman Veenhof and Koster, {Remco A} and Alffenaar, {Jan-Willem C} and {van den Berg}, {Aad P} and {de Groot}, {Marco R} and Verschuuren, {Erik A M} and Berger, {Stefan P} and Bakker, {Stephan J L} and Touw, {Daan J}",
year = "2019",
month = dec,
doi = "10.1515/cclm-2019-0053",
language = "English",
volume = "57",
pages = "1854--1862",
journal = "Clinical chemistry and laboratory medicine",
issn = "1434-6621",
publisher = "Walter de Gruyter GmbH",
number = "12",

}

RIS

TY - JOUR

T1 - Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients

AU - Veenhof, Herman

AU - Koster, Remco A

AU - Alffenaar, Jan-Willem C

AU - van den Berg, Aad P

AU - de Groot, Marco R

AU - Verschuuren, Erik A M

AU - Berger, Stefan P

AU - Bakker, Stephan J L

AU - Touw, Daan J

PY - 2019/12

Y1 - 2019/12

N2 - Background: Monitoring of immunosuppressive drugs such as everolimus and sirolimus is important in allograft rejection prevention in transplant patients. Dried blood spots (DBS) sampling gives patients the opportunity to sample a drop of blood from a fingerprick at home, which can be sent to the laboratory by mail.Methods: A total of 39 sirolimus and 44 everolimus paired fingerprick DBS and whole blood (WB) samples were obtained from 60 adult transplant patients for method comparison using Passing-Bablok regression. Bias was assessed using Bland-Altman. Two validation limits were pre-defined: limits of analytical acceptance were set at >67% of all paired samples within 20% of the mean of both samples and limits of clinical relevance were set in a multidisciplinary team at >80% of all paired samples within 15% of the mean of both samples.Results: For both sirolimus and everolimus, Passing-Bablok regression showed no differences between WB and DBS with slopes of 0.86 (95% CI slope, 0.72-1.02) and 0.96 (95% CI 0.84-1.06), respectively. Only everolimus showed a significant constant bias of 4%. For both sirolimus and everolimus, limits of analytical acceptance were met (76.9% and 81.8%, respectively), but limits or clinical relevance were not met (77.3% and 61.5%, respectively).Conclusions: Because pre-defined limits of clinical relevance were not met, this DBS sampling method for sirolimus and everolimus cannot replace WB sampling in our center at this time. However, if the clinical setting is compatible with less strict limits for clinical relevance, this DBS method is suitable for clinical application.

AB - Background: Monitoring of immunosuppressive drugs such as everolimus and sirolimus is important in allograft rejection prevention in transplant patients. Dried blood spots (DBS) sampling gives patients the opportunity to sample a drop of blood from a fingerprick at home, which can be sent to the laboratory by mail.Methods: A total of 39 sirolimus and 44 everolimus paired fingerprick DBS and whole blood (WB) samples were obtained from 60 adult transplant patients for method comparison using Passing-Bablok regression. Bias was assessed using Bland-Altman. Two validation limits were pre-defined: limits of analytical acceptance were set at >67% of all paired samples within 20% of the mean of both samples and limits of clinical relevance were set in a multidisciplinary team at >80% of all paired samples within 15% of the mean of both samples.Results: For both sirolimus and everolimus, Passing-Bablok regression showed no differences between WB and DBS with slopes of 0.86 (95% CI slope, 0.72-1.02) and 0.96 (95% CI 0.84-1.06), respectively. Only everolimus showed a significant constant bias of 4%. For both sirolimus and everolimus, limits of analytical acceptance were met (76.9% and 81.8%, respectively), but limits or clinical relevance were not met (77.3% and 61.5%, respectively).Conclusions: Because pre-defined limits of clinical relevance were not met, this DBS sampling method for sirolimus and everolimus cannot replace WB sampling in our center at this time. However, if the clinical setting is compatible with less strict limits for clinical relevance, this DBS method is suitable for clinical application.

KW - dried blood spots

KW - immunosuppressants

KW - microsampling

KW - validation

KW - CYCLOSPORINE-A

KW - REGRESSION PROCEDURES

KW - TACROLIMUS

KW - VALIDATION

KW - MS/MS

KW - HEMATOCRIT

KW - CREATININE

KW - SAMPLES

U2 - 10.1515/cclm-2019-0053

DO - 10.1515/cclm-2019-0053

M3 - Article

C2 - 30939110

VL - 57

SP - 1854

EP - 1862

JO - Clinical chemistry and laboratory medicine

JF - Clinical chemistry and laboratory medicine

SN - 1434-6621

IS - 12

ER -

ID: 79153032