title: Dasatinib as salvage therapy for steroid refractory and imatinib resistant or intolerant sclerotic chronic graft-versus-host disease.
abstract: Sclerotic chronic graft-versus-host disease (scGVHD) is a severe form of this disease that resembles systemic sclerosis and has limited and disappointing treatment options. Tyrosine kinase inhibitors (TKI) targeting up-regulated profibrotic pathways, such as imatinib mesylate, have been proposed as a potential therapeutic approach for patients with scGVHD. Dasatinib, a second-generation TKI with a well-established safety and efficacy profile in chronic myeloid leukemia patients, who are refractory or intolerant to imatinib, has also shown potent antifibrotic effects. We present here the first direct clinical evidence, from 3 patients treated in a small single-center series, suggesting that dasatinib can be a therapeutic option for patients with severe scGVHD resistant or intolerant to imatinib. All patients achieved partial response, with improvement in scGHVD target organs severity, joint mobility, lung impairment, and deep fibrotic lesions. This clinical response has remained stable or continued to improve after a median of 22 months (20-25) on dasatinib treatment, with very good tolerance. In addition, corticosteroids could be discontinued or significantly reduced in all patients. This clinical evidence suggests that dasatinib could be a safe and effective alternative for scGVHD patients refractory to corticosteroids and resistant or intolerant to imatinib. Based on these preliminary findings, and in order to address appropriate patient selection, time of intervention, and choice of drug, future larger studies should more formally establish the efficacy and safety of second-generation TKI for the treatment of scGVHD.
authors: Department of Clinical Hematology, Catalan Institute of Oncology, Hospital Duran i Reynals, Av. Gran Vía No. 199-203, Hospitalet de Llobregat, Barcelona, Spain
authors: Isabel
authors: I
authors: Sánchez-Ortega
authors: Octavio
authors: O
authors: Servitje
authors: Montserrat
authors: M
authors: Arnan
authors: Guillermo
authors: G
authors: Ortí
authors: Teresa
authors: T
authors: Peralta
authors: Federico
authors: F
authors: Manresa
authors: Rafael F
authors: RF
authors: Duarte
mesh_terms: D000328:Adult; D001549:Benzamides; D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D000069439:Dasatinib; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D016879:Salvage Therapy / Q000379:methods*; D012598:Sclerosis; D012871:Skin Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D014184:Transplantation, Homologous
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib