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Overlap chronic GVHD is associated with adverse survival outcomes compared to classic chronic GVHD

Bone Marrow Transplantation (2024)Cite this article

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Abstract

Chronic graft-versus-host-disease (cGVHD) is divided into two subtypes: classic (absence of acute GVHD features) and overlap cGVHD (‘ocGVHD’), in which both chronic and acute GVHD clinical features are present simultaneously. While worse outcomes with ocGVHD have been reported, there are few recent analyses. We performed a secondary analysis of data from the ABA2 trial (N = 185), in which detailed GVHD data were collected prospectively and systematically adjudicated. Analyses included cumulative incidence of classic versus ocGVHD, their specific organ manifestations, global disease severity scores, non-relapse mortality (NRM), disease-free survival (DFS) and overall survival (OS) in these two cGVHD subtypes. Of 92 patients who developed cGVHD, 35 were classified as ocGVHD. The 1-year cumulative incidence, organ involvement, and global severity of classic and ocGVHD were similar between ABA2 patients receiving CNI/MTX+placebo and CNI/MTX+abatacept; thus, cohorts were combined for ocGVHD evaluation. This analysis identified ocGVHD as having significantly higher severity at presentation and at maximum global severity compared to classic cGVHD. OS and DFS were significantly lower for ocGVHD versus classic cGVHD. OcGVHD is associated with increased cGVHD severity scores, and is associated with decreased OS and DFS compared to classic cGVHD, underscoring the high risks with this cGVHD subtype.

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Fig. 1: One-year cumulative incidence of cGVHD by ABA2 treatment cohort.
Fig. 2: The distribution of global cGVHD severity scores comparing classic cGVHD to ocGVHD.
Fig. 3: Contribution of the aGVHD component to the global severity score of ocGVHD.
Fig. 4: Key outcomes of classic cGVHD versus ocGVHD.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author notes

  1. These authors jointly supervised this work: Leslie S. Kean, Muna Qayed.

Authors and Affiliations

  1. Boston Children’s Hospital, Dana-Farber Cancer Institute, Boston, MA, USA

    Lev Gorfinkel, Brandi Bratrude, Kayla Betz, Alison Yu, Christine Duncan, John T. Horan & Leslie S. Kean

  2. Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, and Emory University, Atlanta, GA, USA

    Sharmila Raghunandan, Benjamin Watkins & Muna Qayed

  3. Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA

    Kyle Hebert & Donna S. Neuberg

  4. University of Michigan, Ann Arbor, MI, USA

    Sung W. Choi & Gregory A. Yanik

  5. BC Children’s Hospital, University of British Columbia, Vancouver, BC, Canada

    Jeffrey Davis & Kirk R. Schultz

  6. Center for Cancer and Blood Disorders, Children Hospital of Colorado, University of Colorado, Aurora, CO, USA

    Roger Giller

  7. University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Michael Grimley

  8. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Andrew C. Harris

  9. Children’s National Health System, Washington, DC, USA

    David Jacobsohn

  10. University of California San Francisco, UCSF Benioff Children’s Hospital Oakland, Oakland, CA, USA

    Nahal Lalefar

  11. University of Florida, Gainesville, FL, USA

    Nosha Farhadfar

  12. University of Utah, Primary Children’s Hospital, Salt Lake City, UT, USA

    Michael A. Pulsipher

  13. Washington University School of Medicine, St Louis, MO, USA

    Shalini Shenoy

  14. Seattle Children’s Hospital and Fred Hutch Cancer Center, Seattle, WA, USA

    Aleksandra Petrovic

  15. University of Minnesota, Department of Pediatrics, Division of Blood and Marrow Transplantation, Minneapolis, MN, USA

    Bruce R. Blazar

  16. Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Amelia Langston

Authors
  1. Lev Gorfinkel
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Contributions

Conception and design: Lev Gorfinkel, Sharmila Raghunandan, Benjamin Watkins, Muna Qayed, Amelia Langston, John T. Horan, Leslie S. Kean. Provision of study materials or patients: Muna Qayed, Sung W. Choi, Jeffery Davis, Christine Duncan, Roger Giller, Michael Grimley, Andrew C. Harris, David Jacobsohn, Nahal Lalefar, Nosha Farhadfar, Michael A. Pulsipher, Shalini Shenoy, Aleksandra Petrovic, Kirk R. Schultz, Amelia Langston, John T. Horan, Leslie S. Kean. Collection and assembly of data: Lev Gorfinkel, Sharmila Raghunandan, Kyle Hebert, Donna Neuberg, Muna Qayed, Benjamin Watkins, Brandi Bratrude, Kayla Betz, Alison Yui, Sung W. Choi, Jeffery Davis, Christine Duncan, Roger Giller, Michael Grimley, Andrew C. Harris, David Jacobsohn, Nahal Lalefar, Nosha Farhadfar, Michael A. Pulsipher, Shalini Shenoy, Aleksandra Petrovic, Kirk R. Schultz, Amelia Langston, John T. Horan, Leslie S. Kean. Data analysis and interpretation: Lev Gorfinkel, Sharmila Raghunandan, Muna Qayed, Kyle Hebert, Donna Neuberg, Muna Qayed, Benjamin Watkins, Leslie S. Kean. Manuscript writing: All authors. Final approval of manuscript: All authors. Accountable for all aspects of the work: All authors.

Corresponding authors

Correspondence to Leslie S. Kean or Muna Qayed.

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Competing interests

MQ. Consulting or Advisory Role: Novartis, Mesoblast. Travel, Accommodations, Expenses: Novartis. LSK. Consulting or Advisory Role: HiFiBio, Mammoth Biosciences. Research Funding: Regeneron, Gilead Sciences, Novartis, Tessera Therapeutics, Tonix Pharmaceuticals, Bristol Myers Squibb. Patents, Royalties, Other Intellectual Property: Licensing Fees for ABA2 clinical trial data. No other potential conflicts of interest were reported.

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Gorfinkel, L., Raghunandan, S., Watkins, B. et al. Overlap chronic GVHD is associated with adverse survival outcomes compared to classic chronic GVHD. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02245-y

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