Repurposing Nilotinib for Cytomegalovirus Infection Prophylaxis after Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Arm, Phase II Trial.
Biol Blood Marrow Transplant
; 24(11): 2310-2315, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-30026110
ABSTRACT
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.).
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
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Proteínas Tirosina Quinases
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Infecções por Citomegalovirus
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Transplante de Células-Tronco Hematopoéticas
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Condicionamento Pré-Transplante
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Biol Blood Marrow Transplant
Assunto da revista:
HEMATOLOGIA
/
TRANSPLANTE
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Taiwan