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Predictors and outcomes of flares in chronic graft-versus-host disease

Bone Marrow Transplantation volume 57, pages 790–794 (2022)Cite this article

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Abstract

Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT) requires prolonged immunosuppressive therapy (IST), often requiring slow tapering with patients experiencing cGVHD flares and treatment failure. In 145 adult recipients developing cGVHD after matched sibling or umbilical cord blood donor HCT from 2010 to 2018, 2-year cumulative incidence of flares after cGVHD diagnosis was estimated at 60% (95% CI, 51–70%), with median time-to-first flare of 188 days (range, 16–751). Of 88 patients experiencing a flare, 32 (36%) had multiple flares (range, 2–4). First flare treatment consisted of an increase in prednisone dose in 77 patients (88%), plus topical therapy in 8 (9%) or another systemic IST in 43 patients (49%). Higher flare risk was associated with quiescent type of cGVHD at onset (HR 1.8; 95% CI: 1.1–2.7; p = 0.04). Patients without a flare required a shorter duration of IST and were more likely to achieve a durable discontinuation of systemic IST (86% vs. 31% for ≥6 consecutive months). Flares were associated with protective effect on relapse (HR 0.2, 95% CI: 0.1–0.3), however not with worsened 2-year NRM or OS. Flares of cGVHD identify a group needing better approaches to limit the duration of IST and thus the morbidity of cGVHD.

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Fig. 1: Multivariate regression of risk factors for development of cGVHD flare.

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All data generated or analyzed during this study are included in this published article. There is no data available or eligible to be made accessible.

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Acknowledgements

We would like to acknowledge Michael Franklin, MS, for assistance in editing this paper.

Funding

This research was supported by NIH grant P30 CA77598 utilizing the Biostatistics Core of the Masonic Cancer Center, University of Minnesota and the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR002494.

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Authors and Affiliations

  1. Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, USA

    Najla El Jurdi, Grigori Okoev, Shernan G. Holtan, Brian C. Betts, Claudio G. Brunstein, Daniel J. Weisdorf & Mukta Arora

  2. Biostatistics and Informatics, Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN, USA

    Todd E. DeFor

  3. Departments of Medicine and Pediatrics, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA

    Bruce R. Blazar & Margaret L. MacMillan

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  1. Najla El Jurdi
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Contributions

NEJ, GO, and MA performed the retrospective chart reviews; NEJ performed the bibliographic search and wrote the first version of the paper; NEJ and MM contributed to the design; TD performed the statistical analysis; all other authors edited and revised the paper.

Corresponding author

Correspondence to Najla El Jurdi.

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Competing interests

The authors declare the following competing interests, none of which is directly relevant to this work. BRB—receives remuneration as an advisor to Magenta Therapeutics and BlueRock Therapeutics; research funding from BlueRock Therapeutics, Rheos Medicines, Equilibre biopharmaceuticals, Carisma Therapeutics, Inc., and is a co-founder of Tmunity Therapeutics. SGH—consultant for Incyte, Bristol Meyers Squibb, and Generon. DJW—research support from Incyte.

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El Jurdi, N., Okoev, G., DeFor, T.E. et al. Predictors and outcomes of flares in chronic graft-versus-host disease. Bone Marrow Transplant 57, 790–794 (2022). https://doi.org/10.1038/s41409-022-01628-3

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