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Steroid-free first line treatment of moderate and severe chronic GVHD: a survey from the Transplant Complications Working Party of the EBMT

Bone Marrow Transplantation volume 58, pages 325–327 (2023)Cite this article

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Corticosteroids were established as the standard first line systemic treatment of chronic graft-versus-host disease (cGVHD) more than four decades ago [1]. Later attempts to improve the outcomes by using corticosteroids in combination with other immunosuppressive treatments demonstrated no improvement in survival compared to corticosteroids alone [2]. On the other hand, long-term administration of corticosteroids increases the risk of life-threatening infectious complications, leads to Cushing syndrome, bone loss, diabetes, avascular necrosis, myodystrophy, dyslipidemia, hypertension, suppressed growth in children, cataract, glaucoma and chronic adrenal insufficiency. All these complications create a significant healthcare burden on transplant centers and local providers [3]. Furthermore it was demonstrated that less than a half of patients have complete resolution of all cGVHD manifestations after systemic treatment, but rather either reduce or completely discontinue systemic immunosuppressive therapy with topically manageable residual cGVHD symptoms [4]. These two later factors have driven transplantation physicians to explore immunosuppressive approaches with reduced number of complications compared to corticosteroids. These alterations in clinical practice were further encouraged by introduction of new GVHD prophylaxis regimens, including ones without calcineurin inhibitors [5], and effective second-line options for cGVHD treatment that allow tapering and discontinuation of corticosteroids [6, 7]. Nonetheless, no prospective or large retrospective studies are published using these strategies in the first line systemic treatment of moderate and severe cGVHD by National Cacner Institute definitions. Thus a survey was conducted (Supplementary text S1) among all member centers of European Society for Blood and Marrow Transplantation (EBMT) performing allogeneic stem cell transplantation (HSCT) evaluating if steroid-free regimens are used in clinical practice. Statistical methods are presented in supplementary text S2.

The majority of centers (59.2%) reported that steroid-free treatment was used only in a minority of cGVHD patients (defined by questionnaire as <10%), while 12 centers use this strategy in 10–20% of patients, 4 centers in 20–30%, 3 centers in 30–50% and only one in the majority of patients. The choice of steroid-free regimen was rarely dictated by underlying disease. Only 3 centers prefer to use this approach in myelofibrosis and one in non-hodgkin lymphomas. The rest reported that the decision is driven by other clinical factors, predominantly either ongoing severe infectious complications (63.3%) or concern for potential infectious complications (59.2%). Among infectious complications the responders highlighted the significance of fungal (44.9%), viral infections (44.9%) and to a lesser extent bacterial infections (28.6%) when choosing steroid-free approach. Another significant factor to avoid corticosteroids was presence of severe comorbidities (44.9%), including diabetes, severe osteoporosis, avascular osteonecrosis, preexisting myopathy, sarcopenia, poor performance status, obesity and metabolic syndrome, hypertension and uncontrolled psychiatric disorder. Several centers reported that neutropenia (2.0%), lymphopenia (10.2%) and patient preference (10.2%) might drive the choice of treatment (Fig. 1c). Underlying malignancy status was considered as additional factor when choosing steroid-free treatment by 53.1% of centers. Previous hematological relapse (8.16%), minimal residual disease (10.2%) or both (34.7%) were considered when choosing steroid-free approach. Also 22.45% considered mixed chimerism affecting their judgment regarding cGVHD steroid-free treatment. On the contrary, nor risk of COVID-19 (93.9%), neither active COVID-19 infection (87.8%) significantly affected clinical decision towards steroid-free regimens. The respondents commented that usually they postpone treatment until clearance of COVID-19.

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Fig. 1: Key information from the survey.

Data availability

For primary data please contact EBMT study office, pascale.ambron@ebmt.org.

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Acknowledgements

We thank all the centers that showed interest in this problem and responded to the survey.

Author information

Authors and Affiliations

  1. RM Gorbacheva Research Institute, Pavlov University, Lva Tolstogo St. 6/8, Saint Petersburg, Russian Federation

    Ivan Moiseev

  2. EBMT Paris Study Office; Department of Haematology, Saint Antoine Hospital; INSERM UMR 938, Sorbonne University, Paris, France

    Pascale Ambron, Manuela Badoglio & Christophe Peczynski

  3. Department of Hematology, Oncology and Internal Medicine, University Clinical Center of the Medical University of Warsaw, Warsaw, Poland

    Grzegorz Basak

  4. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hanover, Germany

    Christian Koenecke

  5. Department of Hematology, University Hospitals Leuven, KU Leuven, Leuven, Belgium

    Helene Schoemans

  6. Department of Public Health and Primary Care, ACCENT VV, KU Leuven-University of Leuven, Leuven, Belgium

    Helene Schoemans

  7. Department of Hematology, Oncology and Tumorimmunology, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Olaf Penack

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

    Zinaida Peric

  9. University Hospital Centre Zagreb, Zagreb, Croatia

    Zinaida Peric

Authors
  1. Ivan Moiseev
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  2. Pascale Ambron
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  9. Zinaida Peric
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Contributions

IM: conceptualization, methodology, project administration, writing - original draft, visualization; PA: investigation, data curation; MB: methodology, validation; CP: dormal analysis; GB: methodology, writing - review & editing; CK: methodology, writing - review & editing; HS: methodology, writing – review & editing; OP: methodology, writing – review & editing; ZP: methodology, writing – review & editing, supervision.

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Correspondence to Ivan Moiseev.

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Moiseev, I., Ambron, P., Badoglio, M. et al. Steroid-free first line treatment of moderate and severe chronic GVHD: a survey from the Transplant Complications Working Party of the EBMT. Bone Marrow Transplant 58, 325–327 (2023). https://doi.org/10.1038/s41409-022-01881-6

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