TY - JOUR
T1 - National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease
T2 - IV. The 2020 Highly morbid forms report
AU - Wolff, Daniel
AU - Radojcic, Vedran
AU - Lafyatis, Robert
AU - Cinar, Resat
AU - Rosenstein, Rachel K.
AU - Cowen, Edward W.
AU - Cheng, Guang Shing
AU - Sheshadri, Ajay
AU - Bergeron, Anne
AU - Williams, Kirsten M.
AU - Todd, Jamie L.
AU - Teshima, Takanori
AU - Cuvelier, Geoffrey D.E.
AU - Holler, Ernst
AU - McCurdy, Shannon R.
AU - Jenq, Robert R.
AU - Hanash, Alan M.
AU - Jacobsohn, David
AU - Santomasso, Bianca D.
AU - Jain, Sandeep
AU - Ogawa, Yoko
AU - Steven, Philipp
AU - Luo, Zhonghui Katie
AU - Dietrich-Ntoukas, Tina
AU - Saban, Daniel
AU - Bilic, Ervina
AU - Penack, Olaf
AU - Griffith, Linda M.
AU - Cowden, Meredith
AU - Martin, Paul J.
AU - Greinix, Hildegard T.
AU - Sarantopoulos, Stefanie
AU - Socie, Gerard
AU - Blazar, Bruce R.
AU - Pidala, Joseph
AU - Kitko, Carrie L.
AU - Couriel, Daniel R.
AU - Cutler, Corey
AU - Schultz, Kirk R.
AU - Pavletic, Steven Z.
AU - Lee, Stephanie J.
AU - Paczesny, Sophie
N1 - Publisher Copyright:
© 2021 The American Society for Transplantation and Cellular Therapy
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - Allogeneic hematopoietic cell transplantation
KW - Chronic graft-versus-host disease
KW - Consensus
KW - Gastrointestinal tract
KW - Lung
KW - Ocular
KW - Sclerosis
KW - Skin
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U2 - 10.1016/j.jtct.2021.06.001
DO - 10.1016/j.jtct.2021.06.001
M3 - Article
C2 - 34217703
AN - SCOPUS:85114097549
SN - 2666-6367
VL - 27
SP - 817
EP - 835
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 10
ER -