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High incidence of resistant breakthrough invasive fungal infections (IFD) in patients treated for acute gastrointestinal graft-versus-host disease (GI GVHD) following allogeneic haematopoietic cell transplantation

Bone Marrow Transplantation volume 57, pages 1712–1715 (2022)Cite this article

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Haematopoietic cell transplant (HCT) recipients who develop acute graft versus host disease (aGVHD) are at risk of invasive fungal disease (IFD) due to immune dysregulation, disrupted mucosal barriers, and immune suppressive therapy [1]. Historically, for aGVHD patients, IFD predominantly comprised sinopulmonary infections with Invasive Aspergillosis (IA); however, the introduction of broad-spectrum anti-mould azole prophylaxis (posaconazole, voriconazole) [2, 3] significantly reduced breakthrough IFD incidence. Despite widespread azole use, breakthrough IFD, defined using the European Organisation for the Research and Treatment of Cancer (EORTC) criteria [4, 5], still occur during aGVHD treatment at an incidence of at least 2.3–3.4% when restricted to proven and probable cases, and up to 13% when possible cases are included [3, 6, 7]. Because aGVHD is clinically and biologically heterogeneous, the immunological, host and mycological factors contributing to breakthrough IFD are yet to be elucidated.

Site of GVHD organ involvement likely contributes to IFD pathogenesis. Gastrointestinal tract involvement (GI GVHD) results in intestinal dysbiosis and disrupted mucosal barriers [8], potentially impairing absorption of oral antifungal prophylaxis, and supportive care involves use of central lines and parenteral nutrition which are themselves co-factors for IFD [1]. GI GVHD has been associated with breakthrough IFD [9], and steroid-refractory or dependent aGVHD (SR/SD-aGVHD), a state of profound immunosuppression due to GVHD biology and the effects of its escalated anti-GVHD treatment, is a scenario highly conducive to breakthrough IFD [10]. Finally, there are emerging mycological reports that anti-mould prophylaxis directed against common IA species may in fact drive the breakthrough of other invasive, treatment-resistant mould species [11, 12].

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All data generated or analysed during this study are included in this published article and its supplementary appendix.

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Authors and Affiliations

  1. Department of Haematology and Bone Marrow Transplant, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia

    Yin Yuan, Philip Wong, Jason P. Butler, Andrea Henden, Cameron Curley, Simon Durrant, Heshani Mediwake, A. James Morton, Caroline Stewart, Elango Subramoniapillai, Nicholas Weber, Siok-Keen Tey, Glen A. Kennedy & Ashleigh P. Scott

  2. School of Medicine, The University of Queensland, Brisbane, Queensland, Australia

    Yin Yuan, Philip Wong, Siok-Keen Tey, Glen A. Kennedy & Ashleigh P. Scott

  3. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    Andrea Henden & Siok-Keen Tey

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  1. Yin Yuan
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Contributions

APS conceived of and designed the study. APS and all other co-authors contributed patient data through direct patient care. YY, PW and APS performed data collection and analysis, and wrote the manuscript. All authors reviewed and contributed to the final draft of the manuscript.

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Correspondence to Ashleigh P. Scott.

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Yuan, Y., Wong, P., Butler, J.P. et al. High incidence of resistant breakthrough invasive fungal infections (IFD) in patients treated for acute gastrointestinal graft-versus-host disease (GI GVHD) following allogeneic haematopoietic cell transplantation. Bone Marrow Transplant 57, 1712–1715 (2022). https://doi.org/10.1038/s41409-022-01773-9

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