title: Novel targets in the treatment of chronic graft-versus-host disease.
abstract: Despite advances that have improved survival after allogeneic hematopoietic stem cell transplantation (HCT), chronic graft-versus-host disease (GVHD) remains a leading cause of late morbidity and mortality after transplant. Current treatment options show limited efficacy in steroid-refractory disease, and there exists a paucity of robust data to guide management decisions. Lack of United States Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-approved agents in GVHD underscore the importance of developing novel therapies. Better understanding of the biology of chronic GVHD has provided novel targets for treatment, and structured guidelines in diagnosis and in clinical trial design have provided a common language and pathways for research in this area. These, combined with the surge of drug development in Oncology and Immunology, are factors that have contributed to the accelerating field of drug development and clinical research in chronic GVHD. In these exciting times, it is possible to foresee long awaited advances in the treatment of this devastating complication of HCT. This review will summarize the ongoing clinical development for novel therapies in chronic GVHD.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh Cancer Institute and UPMC Cancer Centers, Pittsburgh, PA, USA.|Experimental Transplantation and Immunology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Im
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: F T
authors.initials: FT
authors.lastname: Hakim
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Pavletic
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D002908:Chronic Disease; D055808:Drug Discovery; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy; D061988:Proteasome Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D053823:Hedgehog Proteins; D007155:Immunologic Factors; D060889:Inducible T-Cell Co-Stimulator Protein; D061988:Proteasome Inhibitors; D047428:Protein Kinase Inhibitors; D049349:Receptors, Lysosphingolipid; D053612:Janus Kinases; D019272:Leukocyte Elastase