National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report

Daniel Wolff, Vedran Radojcic, Robert Lafyatis, Resat Cinar, Rachel K. Rosenstein, Edward W. Cowen, Guang Shing Cheng, Ajay Sheshadri, Anne Bergeron, Kirsten M. Williams, Jamie L. Todd, Takanori Teshima, Geoffrey D.E. Cuvelier, Ernst Holler, Shannon R. McCurdy, Robert R. Jenq, Alan M. Hanash, David Jacobsohn, Bianca D. Santomasso, Sandeep JainYoko Ogawa, Philipp Steven, Zhonghui Katie Luo, Tina Dietrich-Ntoukas, Daniel Saban, Ervina Bilic, Olaf Penack, Linda M. Griffith, Meredith Cowden, Paul J. Martin, Hildegard T. Greinix, Stefanie Sarantopoulos, Gerard Socie, Bruce R. Blazar, Joseph Pidala, Carrie L. Kitko, Daniel R. Couriel, Corey Cutler, Kirk R. Schultz, Steven Z. Pavletic, Stephanie J. Lee, Sophie Paczesny

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Chronic graft-versus-host disease (GVHD) can be associated with significant morbidity, in part because of nonreversible fibrosis, which impacts physical functioning (eye, skin, lung manifestations) and mortality (lung, gastrointestinal manifestations). Progress in preventing severe morbidity and mortality associated with chronic GVHD is limited by a complex and incompletely understood disease biology and a lack of prognostic biomarkers. Likewise, treatment advances for highly morbid manifestations remain hindered by the absence of effective organ-specific approaches targeting “irreversible” fibrotic sequelae and difficulties in conducting clinical trials in a heterogeneous disease with small patient numbers. The purpose of this document is to identify current gaps, to outline a roadmap of research goals for highly morbid forms of chronic GVHD including advanced skin sclerosis, fasciitis, lung, ocular and gastrointestinal involvement, and to propose strategies for effective trial design. The working group made the following recommendations: (1) Phenotype chronic GVHD clinically and biologically in future cohorts, to describe the incidence, prognostic factors, mechanisms of organ damage, and clinical evolution of highly morbid conditions including long-term effects in children; (2) Conduct longitudinal multicenter studies with common definitions and research sample collections; (3) Develop new approaches for early identification and treatment of highly morbid forms of chronic GVHD, especially biologically targeted treatments, with a special focus on fibrotic changes; and (4) Establish primary endpoints for clinical trials addressing each highly morbid manifestation in relationship to the time point of intervention (early versus late). Alternative endpoints, such as lack of progression and improvement in physical functioning or quality of life, may be suitable for clinical trials in patients with highly morbid manifestations. Finally, new approaches for objective response assessment and exploration of novel trial designs for small populations are required.

Original languageEnglish (US)
Pages (from-to)817-835
Number of pages19
JournalTransplantation and Cellular Therapy
Issue number10
StatePublished - Oct 2021

Bibliographical note

Publisher Copyright:
© 2021 The American Society for Transplantation and Cellular Therapy


  • Allogeneic hematopoietic cell transplantation
  • Chronic graft-versus-host disease
  • Consensus
  • Gastrointestinal tract
  • Lung
  • Ocular
  • Sclerosis
  • Skin


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