https://scholars.lib.ntu.edu.tw/handle/123456789/479702
標題: | Repurposing Nilotinib for Cytomegalovirus Infection Prophylaxis after Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Arm, Phase II Trial | 作者: | Lin C.-T. PO-REN HSUEH SHANG-JU WU MING YAO BOR-SHENG KO Li C.-C. Hsu C.-A. JIH-LUH TANG HWEI-FANG TIEN |
公開日期: | 2018 | 卷: | 24 | 期: | 11 | 起(迄)頁: | 2310-2315 | 來源出版物: | Biology of Blood and Marrow Transplantation | 摘要: | Platelet-derived growth factor receptor-alpha (PDGFRa) is a critical receptor for cytomegalovirus (CMV) entry into cells, leading to subsequent infection. This trial tested whether PDGFRa inhibition by nilotinib could prevent CMV infection in patients after allogeneic stem cell transplantation (allo-HSCT). Nilotinib (200 mg/day) was given continuously after engraftment, and plasma CMV DNA levels were monitored weekly. The primary endpoint was successful prophylaxis of CMV infection, defined as plasma CMV DNA copies less than 10,000 copies/mL, no anti-CMV treatment initiated, and no clinical CMV disease by day 100. All 37 enrolled recipients and their donors were CMV seropositive. Thirty patients received matched sibling transplants, 15 received nonmyeloablative conditioning regimens, and 15 received antithymocyte globulin as a part of graft-versus-host disease prophylaxis. The median interval from transplantation to nilotinib treatment was 23 days, and the median duration of administration was 76 days. None of the 31 assessable patients had nilotinib-associated grade 3/4 adverse events or nilotinib discontinuation. Twenty-five of 31 assessable patients (80.6%) fulfilled the predefined criteria for successful CMV prophylaxis, and none of them had clinical CMV disease. Only 1 of 6 failed patients developed CMV colitis. Nilotinib is well tolerated in allo-HSCT recipients, and its preliminary efficacy results suggest that blocking CMV entry to prevent CMV infection may warrant further exploration. (ClinicalTrials.gov identifier: NCT01252017.) ? 2018 |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/479702 | ISSN: | 1083-8791 | DOI: | 10.1016/j.bbmt.2018.07.013 | SDG/關鍵字: | cyclosporine; fludarabine; ganciclovir; nilotinib; platelet derived growth factor alpha receptor; steroid; thymocyte antibody; virus DNA; 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide; protein tyrosine kinase; pyrimidine derivative; acute biphenotypic leukemia; acute graft versus host disease; acute lymphoblastic leukemia; acute myeloid leukemia; adult; aged; allogeneic hematopoietic stem cell transplantation; anemia; anorexia; antiviral therapy; Article; blood level; clinical article; colitis; cytomegalovirus infection; diarrhea; drug blood level; drug efficacy; drug megadose; drug repositioning; drug substitution; drug tolerability; drug withdrawal; female; gene dosage; graft versus host reaction; human; hyperbilirubinemia; hypertransaminasemia; infection; infection prevention; male; myelodysplastic syndrome; nausea; nonhodgkin lymphoma; nonmyeloablative conditioning; phase 2 clinical trial; skin disease; steroid therapy; thrombocytopenia; time to treatment; treatment duration; vomiting; allotransplantation; clinical trial; cytomegalovirus infection; hematopoietic stem cell transplantation; middle aged; pathology; procedures; transplantation conditioning; young adult; Adult; Aged; Cytomegalovirus Infections; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Protein-Tyrosine Kinases; Pyrimidines; Transplantation Conditioning; Transplantation, Homologous; Young Adult |
顯示於: | 醫學院附設醫院 (臺大醫院) |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。