Improving the prediction of acute myeloid leukaemia outcomes by complementing mutational profiling withex vivochemosensitivity
| Autor: | Joaquin Martinez-Lopez, Rosa Ayala, Julian Gorrochategui, Jaime Pérez-Oteyza, Inmaculada Rapado, Joan Ballesteros, Eva Barragán, Pau Montesinos, José Luis Rojas, David Martínez-Cuadrón, Esther Onecha, María Linares, Elena Magro, Blanca Boluda, Pilar Martínez-Sánchez, Claudia Sargas, Yanira Ruiz-Heredia, Jesús Villoria, Pilar Herrera |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Oncology Drug medicine.medical_specialty Adolescent media_common.quotation_subject Drug resistance Cohort Studies Young Adult 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Aged media_common Aged 80 and over biology business.industry Hazard ratio EZH2 Hematology Middle Aged Leukemia Myeloid Acute Treatment Outcome KMT2A 030220 oncology & carcinogenesis Mutation Cohort biology.protein Female Myeloid leukaemia business Ex vivo 030215 immunology |
| Zdroj: | British Journal of Haematology. 189:672-683 |
| ISSN: | 1365-2141 0007-1048 |
| DOI: | 10.1111/bjh.16432 |
| Popis: | Refractoriness to induction therapy and relapse after complete remission are the leading causes of death in patients with acute myeloid leukaemia (AML). This study focussed on the prediction of response to standard induction therapy and outcome of patients with AML using a combined strategy of mutational profiling by next-generation sequencing (NGS, n = 190) and ex vivo PharmaFlow testing (n = 74) for the 10 most widely used drugs for AML induction therapy, in a cohort of adult patients uniformly treated according to Spanish PETHEMA guidelines. We identified an adverse mutational profile (EZH2, KMT2A, U2AF1 and/or TP53 mutations) that carries a greater risk of death [hazard ratio (HR): 3·29, P < 0·0001]. A high correlation was found between the ex vivo PharmaFlow results and clinical induction response (69%). Clinical correlation analysis showed that the pattern of multiresistance revealed by ex vivo PharmaFlow identified patients with a high risk of death (HR: 2·58). Patients with mutation status also ran a high risk (HR 4·19), and the risk was increased further in patients with both adverse profiles (HR 4·82). We have developed a new score based on NGS and ex vivo drug testing for AML patients that improves upon current prognostic risk stratification and allows clinicians to tailor treatments to minimise drug resistance. |
| Databáze: | OpenAIRE |
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