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Amniotic membrane transplantation—a new approach to crossing the HLA barriers in the treatment of refractory ocular graft-versus-host disease

Bone Marrow Transplantation volume 53, pages 1466–1469 (2018)Cite this article

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Ocular chronic graft-versus-host disease (oGVHD) occurs in 40-60% of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) [1]. Severe forms of oGVHD can be devastating since they restrict daily activities and severely deteriorate quality of life. The most common clinical manifestations of oGVHD include dry eye syndrome and conjunctival inflammation. Available therapies include a variety of topical and systemic approaches with respect to the severity of the condition. However, there is a lack of effective treatment for steroid refractory disease as well as a paucity of controlled trials in the management of oGVHD. New strategies include autologous tear drops and scleral lenses with some encouraging results [2, 3]. Despite all available therapies, some cases still progress to severe ocular ulcerations and occasionally result in corneal perforation requiring emergency keratoplasty. Moreover, catastrophic consequences with enucleation of the eye and permanent visual impairment have also been described [4].

Amniotic membrane (AM) is an avascular fetal membrane collected from placental tissue during elective cesarean sections, from donors screened for transmissible infectious diseases. As it lacks HLA-A, HLA-B and HLA-DR antigens, AM is universally tolerated and can be used without fear of rejection. Amniotic membrane transplantation (AMT) is an established technique in the treatment of non-healing skin wounds and severe burns [5]. In ophthalmology, AMT was first developed for severe ocular manifestations of acute Stevens-Johnson syndrome [6]. Today it is being efficiently used for the treatment of various types of keratitis, neurotrophic keratopathy, non-healing corneal ulcers and corneal perforations [7]. The application of AM is simple and well tolerated among recipients, with no serious complications following the procedure [8]. AM typically dissolves over a period of 1–2 weeks; thus, more than one application may be necessary during the acute phase of the disease. Topical medications can be used concurrently, as medication penetration has not been found to be an issue. Two types of AM—cryopreserved and dehydrated are approved for distribution as tissue allografts and are commercially available.

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Acknowledgements

This work was supported, in part, by the Unity Through Knowledge Fund project entitled “Clinical and biological factors determining severity and activity of chronic Graft-versus-Host disease after allogeneic hematopoietic stem cell transplantation”, and in part by the Croatian Science Foundation project entitled “New biomarkers for chronic Graft-versus-Host disease”. We thank many members of multidisciplinary team for cGVHD at the University Hospital Center Zagreb, Croatia.

Authors contribution:

ZP collected and analyzed the data and wrote the paper. IS performed AMT and made the Figure and Supplementary Information. ND, LD and DP treated the patients and analyzed the data. RS-S treated the patients and reviewed the manuscript. IP analyzed AMT outcomes and reviewed the manuscript. SZP and RV designed the study and reviewed the manuscript.

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Authors and Affiliations

  1. Department of Hematology, University Hospital Centre, Zagreb, Croatia

    Zinaida Peric, Nadira Durakovic, Lana Desnica, Drazen Pulanic, Ranka Serventi-Seiwerth & Radovan Vrhovac

  2. School of Medicine, University of Zagreb, Zagreb, Croatia

    Zinaida Peric, Nadira Durakovic, Drazen Pulanic, Igor Petricek & Radovan Vrhovac

  3. Department of Ophtalmology, University Hospital Centre, Zagreb, Croatia

    Ivan Skegro & Igor Petricek

  4. National Cancer Institute, , National Institute of Health, Bethesda, MD, USA

    Steven Z. Pavletic

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  1. Zinaida Peric
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Correspondence to Zinaida Peric.

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Peric, Z., Skegro, I., Durakovic, N. et al. Amniotic membrane transplantation—a new approach to crossing the HLA barriers in the treatment of refractory ocular graft-versus-host disease. Bone Marrow Transplant 53, 1466–1469 (2018). https://doi.org/10.1038/s41409-018-0140-6

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