Changes in Chronic Graft-versus-Host Disease Treatment Over Time: A 15-Years Survey Within Allogeneic Hematopoietic Stem Cell Transplant Centers in Germany, Austria, and Switzerland
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background Chronic graft-versus-host disease (cGVHD) represents a major complication after allogeneic stem cell transplantation (alloHSCT). In 2009 and 2018 a survey among German, Austrian, and Swiss transplant centers showed a homogeneous 1 st -line treatment practice, while 2 nd -line treatment as well as management of progressive onset type and bronchiolitis obliterans syndrome (BOS) displayed significant heterogeneity. Since the last survey, ruxolitinib (rux) has been approved and other new agents are explored in treatment of cGVHD. Objective We conducted a follow-up survey in 2024 to document the impact of recent approvals and new agents on treatment pattern focusing on management of 2 nd -line treatment, progressive onset type, BOS, and sclerotic manifestations. Study design A paper-and-pencil-based questionnaire was sent electronically to 60 German speaking centers performing alloHSCT. 20 centers responded, representing 45% of the patients receiving an alloHSCT in 2023 in Germany, Austria, and Switzerland. Results In 1 st -line treatment of classic standard risk cGVHD, single agent prednisone represents standard of care (14/20 centers) which may be combined with calcineurin inhibitor (CNI) (4/20), while rux is used in selected cases only. In 2 nd -line treatment rux is now used by the majority of centers (19/20). In the presence of cytopenia, rux remains the preferred agent (12/20) while use of extracorporeal photopheresis (ECP) is considered by 8 of 20 centers. In case of active infections, ECP is preferred by 15 of 20 centers and both agents are regarded as steroid-sparing agents in 2 nd -line treatment of steroid-dependent cGVHD. Rux would be applied in the presence of active infections by 5/20 centers only. Moreover, rux (15/20) and ECP (6/20) are also preferred treatment modalities in treatment of progressive onset cGVHD. For BOS, systemic and inhalative corticosteroids, montelukast and azithromycin (FAM, 13/20), rux (15/20), ECP (17/20) and CNI (10/20) are frequently applied agents, while abatacept (8/20), belumosudil (7/20), imatinib (5/20), mycophenolate mofetil (MMF) (5/20), everolimus (4/20) and ibrutinib (3/20) are used as salvage options in selected patients only. In case of new sclerotic manifestations after failure of 2 nd -line treatment including steroids, CNI and rux, most centers would use ECP (14/20), whereas subsequent or alternative salvage treatment of sclerotic manifestations remains heterogenous comprising belumosudil (13/20), ibrutinib (5/20), imatinib (5/20), rituximab (4/20), cyclosporine (3/20), tacrolimus (3/20), everolimus (3/20), sirolimus (3/20), methotrexate (3/20) and MMF (3/20). The preferred taper sequence of immunosuppressive agents in case of response applied in 12/20 centers is initial taper of steroids, followed by taper of CNI and final termination of rux. Conclusion The survey documents the effect of evidence and approval on clinical care with single agent prednisone representing the standard of care in 1 st -line treatment while rux combined with steroids defines the new standard for 2 nd -line treatment of cGVHD. ECP is used in case of contraindication for rux and both agents are also used in progressive onset cGVHD. In contrast, treatment of BOS and sclerotic cGVHD beyond 2 nd -line treatment remains heterogeneous with new agents being integrated in the treatment landscape.
Authors: Alexander Denk, Matthias Alexander Fante, Silke Heidenreich, Hildegard T. Greinix, Eva-Maria Wagner Drouet, Katharina Egger-Heidrich, Julia Marx, Darina Kodzhabasheva, William Krüger, Gesine Bug, Claudia Wehr, Joerg Halter, Irene Teichert von Lüttichau, Lutz Peter Mueller, Olaf Penack, Inken Hilgendorf, Guido Kobbe, Stefan Klein, Anita Lawitschka, Jochen Frietsch, Julia Winkler, Daniel Wolff
Institutions: University Hospital Regensburg, University Medical Center Hamburg-Eppendorf, Medical University of Graz, Johannes Gutenberg University Mainz, University Hospital Carl Gustav Carus, Technische Universität Dresden, University of Münster, University Hospital Münster, St.-Johannes-Hospital Dortmund, Universitätsmedizin Greifswald, Universität Greifswald, University Hospital Frankfurt, University of Freiburg, University Hospital of Basel, Technical University of Munich, University Hospital in Halle, Humboldt-Universität zu Berlin, Freie Universität Berlin, Charité - Universitätsmedizin Berlin, Jena University Hospital, Düsseldorf University Hospital, Heidelberg University, University Medical Centre Mannheim, St Anna Children's Hospital, Medical University of Vienna, University of Würzburg, Universitätsklinikum Würzburg, Universitätsklinikum Erlangen
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W4410090651