Abstract
Skin graft versus host disease (GVHD) can affect quality of life in hematopoietic stem cell transplant recipients. Therapeutic options for steroid-refractory GVHD are limited. We report the first prospective pilot study evaluating the topical vitamin D3 analog Calcipotriene (DOVONEX 0.005% cream) for acute skin GVHD in children, with associated analyses of target organ chemokine CXCL10 changes in response to therapy. We observed that Calcipotriene applications were safe and well tolerated. There were no symptom progression nor new symptoms requiring GVHD therapy escalation during study period. The most consistent response observed by study subjects was resolution of pruritus in eight patients and significant improvement in pruritus in two study subjects. Nine of ten patients had improvement or resolution of skin rash. In addition, we documented reduction of CXCL10 levels in the skin of seven subjects with GVHD after Calcipotriene course using non-invasive D-Squame® disc application to the skin for chemokine analysis. Our pilot study shows promising observation that topical Calcipotriene could be a novel therapeutic option for acute skin GVHD, especially in patients presenting with pruritus and should be studied in larger prospective studies.
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References
Holtan SG, Pasquini M, Weisdorf DJ. Acute graft-versus-host disease: a bench-to-bedside update. Blood. 2014;124:363–73. https://doi.org/10.1182/blood-2014-01-514786. e-pub ahead of print 2014/06/11.
Wallace G, Myers KC, Teusink-Cross A, Davies SM, Khandelwal P, Jodele S. Topical vitamin D analog for chronic graft versus host disease of the skin. Bone Marrow Transpl. 2018;53:628–33. https://doi.org/10.1038/s41409-017-0031-2. e-pub ahead of print 2018/01/18.
Maestro MA, Molnar F, Carlberg C. Vitamin D and its synthetic analogs. J. Med. Chem. 2019. https://doi.org/10.1021/acs.jmedchem.9b00208.
Katayama I, Miyazaki Y, Nishioka K. Topical vitamin D3 (tacalcitol) for steroid-resistant prurigo. Br J Dermatol. 1996;135:237–40. e-pub ahead of print 1996/08/01.
Khandelwal P, Smiley K, Fieno AM, Grant RA, Davies SM. CXCL10 can be detected non-invasively from the skin of children with acute skin GvHD. Bone Marrow Transpl. 2016;51:1379–81. https://doi.org/10.1038/bmt.2016.119. e-pub ahead of print 2016/05/10.
Reichrath J, Muller SM, Kerber A, Baum HP, Bahmer FA. Biologic effects of topical calcipotriol (MC 903) treatment in psoriatic skin. J Am Acad Dermatol. 1997;36:19–28. e-pub ahead of print 1997/01/01.
Ikeda U, Wakita D, Ohkuri T, Chamoto K, Kitamura H, Iwakura Y, et al. 1alpha,25-Dihydroxyvitamin D3 and all-trans retinoic acid synergistically inhibit the differentiation and expansion of Th17 cells. Immunol Lett. 2010;134:7–16. https://doi.org/10.1016/j.imlet.2010.07.002. e-pub ahead of print 2010/07/27.
Vanherwegen AS, Cook DP, Ferreira GB, Gysemans C, Mathieu C. Vitamin D-modulated dendritic cells delay lethal graft-versus-host disease through induction of regulatory T cells. J steroid Biochem Mol Biol. 2019;188:103–10. https://doi.org/10.1016/j.jsbmb.2018.12.013. e-pub ahead of print 2019/01/04.
Reinhardt-Heller K, Hirschberg I, Lang P, Vogl T, Handgretinger R, Bethge WA, et al. Increase of intermediate monocytes in graft-versus-host disease: correlation with MDR1(+)Th17.1 levels and the effect of prednisolone and 1alpha,25-Dihydroxyvitamin D3. Biol Blood Marrow Transpl. 2017;23:2057–64. https://doi.org/10.1016/j.bbmt.2017.08.008. e-pub ahead of print 2017/08/16.
Miller J, Gallo RL. Vitamin D and innate immunity. Dermatologic Ther. 2010;23:13–22. https://doi.org/10.1111/j.1529-8019.2009.01287.x. e-pub ahead of print 2010/02/09.
Scolletta S, Colletti M, Di Luigi L, Crescioli C. Vitamin D receptor agonists target CXCL10: new therapeutic tools for resolution of inflammation. Mediators Inflamm. 2013;2013:876319 https://doi.org/10.1155/2013/876319. e-pub ahead of print 2013/05/22.
Baeke F, Korf H, Overbergh L, Verstuyf A, Thorrez L, Van Lommel L, et al. The vitamin D analog, TX527, promotes a human CD4+CD25highCD127low regulatory T cell profile and induces a migratory signature specific for homing to sites of inflammation. J Immunol. 2011;186:132–42. https://doi.org/10.4049/jimmunol.1000695. e-pub ahead of print 2010/12/07.
Acknowledgements
The authors wish to thank the patients and their families participating in this study and the Diagnostic Immunology Laboratory (DIL) team for performing study sample testing. Samples used in this study were collected and provided by the staff of the CCHMC BMT tissue repository who we thank for outstanding ongoing technical assistance.
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Wallace, G., Khandelwal, P., Myers, K.C. et al. Prospective pilot trial of calcipotriene as a novel topical treatment for acute skin graft versus host disease. Bone Marrow Transplant 56, 1441–1444 (2021). https://doi.org/10.1038/s41409-020-01189-3
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DOI: https://doi.org/10.1038/s41409-020-01189-3