title: Imatinib mesylate for the treatment of steroid-refractory sclerotic-type cutaneous chronic graft-versus-host disease.
abstract: Sclerotic skin manifestations of chronic graft-versus-host disease (ScGVHD) lead to significant morbidity, including functional disability from joint range of motion (ROM) restriction. No superior second-line therapy has been established for steroid-refractory disease. Imatinib mesylate is a multikinase inhibitor of several signaling pathways implicated in skin fibrosis with in vitro antifibrotic activity. We performed an open-label pilot phase II trial of imatinib in children and adults with corticosteroid-refractory ScGVHD. Twenty patients were enrolled in a 6-month trial. Eight received a standard dose (adult, 400 mg daily; children, 260 mg/m(2) daily). Because of poor tolerability, 12 additional patients underwent a dose escalation regimen (adult, 100 mg daily initial dose up to 200 mg daily maximum; children, initial dose 65 mg/m(2) daily up to 130 mg/m(2) daily). Fourteen patients were assessable for primary response, improvement in joint ROM deficit, at 6 months. Primary outcome criteria for partial response was met in 5 of 14 (36%), stable disease in 7 of 14 (50%), and progressive disease in 2 of 14 (14%) patients. Eleven patients (79%), including 5 with partial response and 6 with stable disease, demonstrated a positive gain in ROM (range of 3% to 94% improvement in deficit). Of 13 patients with measurable changes at 6 months, the average improvement in ROM deficit was 24.2% (interquartile range, 15.5% to 30.5%; P = .011). This trial is registered at http://clinicaltrials.gov as NCT007020689.
authors.affiliation: Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Kristin
authors.initials: K
authors.lastname: Baird
authors.affiliation: Rehabilitation Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Leora E
authors.initials: LE
authors.lastname: Comis
authors.affiliation: Rehabilitation Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Galen O
authors.initials: GO
authors.lastname: Joe
authors.affiliation: Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Fran T
authors.initials: FT
authors.lastname: Hakim
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Rose
authors.affiliation: Outcomes Research Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, Maryland.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Mitchell
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: Pavletic
authors.affiliation: Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.affiliation: Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Yao
authors.affiliation: Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Flanders
authors.affiliation: Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Naoko
authors.initials: N
authors.lastname: Takebe
authors.affiliation: Division of Hematologic Malignancy and Cell Therapy and Duke Cancer Institute, Department of Medicine, Duke University, Durham, North Carolina.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sarantopoulos
authors.affiliation: Autoimmunity and Mucosal Immunology Branch, National Institute of Allergy and Infectious Diseases, Rockville, Maryland.
authors.forename: Susan
authors.initials: S
authors.lastname: Booher
authors.affiliation: Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: edcowen@hotmail.com.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Cowen
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D004334:Drug Administration Schedule; D005208:Fasciitis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D007596:Joints / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007938:Leukemia / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010865:Pilot Projects; D011241:Prednisone / Q000627:therapeutic use; D016059:Range of Motion, Articular / Q000187:drug effects; D012008:Recurrence; D012871:Skin Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016559:Tacrolimus / Q000627:therapeutic use; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents; D000068877:Imatinib Mesylate; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus
keywords: Allogeneic hematopoietic stem cell transplantation; Fasciitis; Graft-versus-host disease; Imatinib mesylate; Sclerosis