Universität zu Köln

Tahmaz, Volkan, Wiesen, Martin H. J., Gehlsen, Uta ORCID: 0000-0001-9057-9199, Sauerbier, Laura, Stern, Michael E., Holtick, Udo, Gathof, Birgit, Scheid, Christof, Mueller, Carsten and Steven, Philipp (2021). Detection of systemic immunosuppressants in autologous serum eye drops (ASED) in patients with severe chronic ocular graft versus host disease. Graefes Arch. Clin. Exp. Ophthalmol., 259 (1). S. 121 - 129. NEW YORK: SPRINGER. ISSN 1435-702X

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Abstract

Purpose Chronic graft versus host disease is a major consequence after allogeneic stem cell transplantation (allo-SCT) and has great impact on patients' morbidity and mortality. Besides the skin, liver, and intestines, the eyes are most commonly affected, manifesting as severe ocular surface disease. Treatment protocols include topical steroids, cyclosporine, tacrolimus, and ASED. Since these patients often receive systemic immunosuppressant therapy from their oncologists, a topical re-administration of these drugs via ASED with potentially beneficial or harmful effects is possible. The purpose of the study was to determine whether and to which extent systemic immunosuppressants are detectable in ASED. Methods A total of 34 samples of ASED from 16 patients with hemato-oncological malignancies after allo-SCT were collected during the manufacturing process and screened for levels of cyclosporine, mycophenolic acid, everolimus, and tacrolimus via liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The study followed the tenets of the Declaration of Helsinki and informed consent was obtained from the subjects after explanation of the nature and possible consequences of the study. Results Cyclosporine was found in 18 ASED samples in concentrations ranging from 6.5-105.0 ng/ml (32.0 +/- 22.8 ng/ml, mean +/- SD). The concentration range of mycophenolic acid in 19 samples was 0.04-25.0 mg/l (4.0 +/- 5.4 mg/l, mean +/- SD). Everolimus and tacrolimus concentrations were well below the respective limits of quantification (< 0.6 and < 0.5 ng/ml) of the established LC-MS/MS method in all samples. Conclusions Our study suggests that orally administered cyclosporine and mycophenolic acid for the treatment of systemic GvHD, but not everolimus and tacrolimus, are distinctly detectable in ASED in relevant concentrations. It is highly likely that these agents affect topical therapy of ocular GvHD. However, the extent of this effect needs to be evaluated in further studies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tahmaz, Volkan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesen, Martin H. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gehlsen, Uta UNSPECIFIED orcid.org/0000-0001-9057-9199 UNSPECIFIED Sauerbier, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Stern, Michael E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Holtick, Udo UNSPECIFIED UNSPECIFIED UNSPECIFIED Gathof, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheid, Christof UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Steven, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-322979
DOI:	10.1007/s00417-020-04865-8
Journal or Publication Title:	Graefes Arch. Clin. Exp. Ophthalmol.
Volume:	259
Number:	1
Page Range:	S. 121 - 129
Date:	2021
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1435-702X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DRY EYE; BLOOD; PLASMA; TRIAL Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32297