Assuntos
COVID-19/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Adulto , Idoso , Antineoplásicos/uso terapêutico , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/terapia , Comorbidade , Etnicidade , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Resultado do Tratamento , Reino Unido/epidemiologia , Adulto JovemAssuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Complicações Hematológicas na Gravidez/sangue , Complicações Infecciosas na Gravidez/sangue , Púrpura Trombocitopênica Idiopática/complicações , Adulto , COVID-19 , Infecções por Coronavirus/sangue , Feminino , Humanos , Contagem de Linfócitos , Pandemias , Contagem de Plaquetas , Pneumonia Viral/sangue , Gravidez , Púrpura Trombocitopênica Idiopática/sangue , SARS-CoV-2Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Subpopulações de Linfócitos , Pandemias , Pneumonia Viral/sangue , Antibacterianos/uso terapêutico , COVID-19 , Núcleo Celular/ultraestrutura , Terapia Combinada , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Citoplasma/ultraestrutura , Hidratação , Humanos , Contagem de Leucócitos , Subpopulações de Linfócitos/ultraestrutura , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Oxigenoterapia , Contagem de Plaquetas , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , SARS-CoV-2RESUMO
PURPOSE: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms. PATIENTS AND METHODS: MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response. RESULTS: One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P = .02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P < .001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P = .01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P = .03). Serial analysis of JAK2V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P = .001, EFS P = .001, overall survival P = .01) and clearance of JAK2V617F stem/progenitor cells. ASXL1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P = .003). The safety profile of ruxolitinib was as previously reported. CONCLUSION: The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.