Toward a Better Understanding of the Atypical Features of Chronic Graft-Versus-Host Disease: A Report from the 2020 National Institutes of Health Consensus Project Task Force

• Authors: Geoffrey D. E. Cuvelier, University of Manitoba; Michelle Schoettler, Emory University; Nataliya P. Buxbaum, Roswell Park Comprehensive Care Center; Iago Pinal-Fernandez, National Institutes of Health; Marc Schmalzing, University of Wurzburg; Jorg H. W. Distler, University of Erlangen Nurnberg; Olaf Penack, Charite University; Bianca D. Santomasso, Memorial Sloan Kettering Cancer Center; Robert Zeiser, University of Freiburg; Klemens Angstwurm, University Medical Center Regensburg; Kelli P. A. MacDonald, QIMR Berghofer Medical Research Institute; W. Taylor Kimberly, Massachusetts General Hospital; Naomi Taylor, National Institutes of Health; Ervina Bilic, University of Zagreb; Bernhard Banas, University Hospital Regensburg; Maike Buettner-Herold, Friedrich Alexander University; Namita Sinha, University of Manitoba; Hildegard T. Greinix, Medical University of Graz; Joseph Pidala, H Lee Moffitt Cancer Centre & Research Institute; Kirk R. Schultz, BC Children's Hospital; Kirsten Williams, Emory University; Yoshihiro Inamoto, National Cancer Center; Corey Cutler, Dana Farber Cancer Institute; Stephanie J. Lee, Fred Hutchinson Cancer Research Center; Stefanie Sarantopoulos, Duke University; Steven Z. Pavletic, National Institutes of Health; Daniel Wolff, University Hospital Regensburg
• Journal Title: TRANSPLANTATION AND CELLULAR THERAPY
• Volume: Volume 28, Number 8
• Publisher: ELSEVIER SCIENCE INC | 2022-07-30, Pages 426-445
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.jtct.2022.05.038
• Subjects: Health Sciences, Immunology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Hematology; Immunology; Transplantation;   Chronic graft-versus-host disease; Atypical; National Institutes of Health Consensus Project Task Force; STEM-CELL TRANSPLANTATION; AUTOIMMUNE HEMOLYTIC-ANEMIA; CENTRAL-NERVOUS-SYSTEM; BONE-MARROW-TRANSPLANTATION; CORD BLOOD TRANSPLANTATION; TUBULAR BRUSH-BORDER; CD4(+) T-CELLS; CHRONIC GVHD; THROMBOTIC MICROANGIOPATHY; NEUROLOGIC COMPLICATIONS

Abstract

Alloreactive and autoimmune responses after allogeneic hematopoietic cell transplantation can occur in nonclassical chronic graft-versus-host disease (chronic GVHD) tissues and organ systems or manifest in atypical ways in classical organs commonly affected by chronic GVHD. The National Institutes of Health (NIH) consensus projects were developed to improve understanding and classification of the clinical features and diagnostic criteria for chronic GVHD. Although still speculative whether atypical manifestations are entirely due to chronic GVHD, these manifestations remain poorly captured by the current NIH consensus project criteria. Examples include chronic GVHD impacting the hematopoietic system as immune mediated cytopenias, endothelial dysfunction, or as atypical features in the musculoskeletal system, central and peripheral nervous system, kidneys, and serous membranes. These purported chronic GVHD features may contribute significantly to patient morbidity and mortality. Most of the atypical chronic GVHD features have received little study, particularly within multi-institutional and prospective studies, limiting our understanding of their frequency, pathogenesis, and relation to chronic GVHD. This NIH consensus project task force report provides an update on what is known and not known about the atypical manifestations of chronic GVHD while outlining a research framework for future studies to be undertaken within the next 3 to 7 years. We also provide provisional diagnostic criteria for each atypical manifestation, along with practical investigation strategies for clinicians managing patients with atypical chronic GVHD features.