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- Angenendt, Linus, et al.
(författare)
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Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia : A Pooled Analysis of Individual Patient Data From Nine International Cohorts
- 2019
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Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 37:29, s. 2632-2642
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption.METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1(mut)/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers.RESULTS: Among 2,426 patients with NPM1(mut)/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1(mut)/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome.CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1(mut)/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1(mut) share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1(mut)/FLT3-ITDneg/low AML.
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- Bayes de Luna, Antonio, et al.
(författare)
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Interatrial blocks. A separate entity from left atrial enlargement: a consensus report
- 2012
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 45:5, s. 445-451
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Tidskriftsartikel (refereegranskat)abstract
- Impaired interatrial conduction or interatrial block is well documented but is not described as an individual electrocardiographic (ECG) pattern in most of ECG books, although the term atrial abnormalities to encompass both concepts, left atrial enlargement (LAE) and interatrial block, has been coined. In fact, LAE and interatrial block are often associated, similarly to what happens with ventricular enlargement and ventricular block. The interatrial blocks, that is, the presence of delay of conduction between the right and left atria, are the most frequent atrial blocks. These may be of first degree (P-wave duration > 120 milliseconds), third degree (longer P wave with biphasic [+/-] morphology in inferior leads), and second degree when these patterns appear transiently in the same ECG recording (atrial aberrancy). There are evidences that these electrocardiographic P-wave patterns are due to a block because they may (a) appear transiently, (b) be without associated atrial enlargement, and (c) may be reproduced experimentally. The presence of interatrial blocks may be seen in the absence of atrial enlargement but often are present in case of LAE. The most important clinical implications of interatrial block are the following: (a) the first degree interatrial blocks are very common, and their relation with atrial fibrillation and an increased risk for global and cardiovascular mortality has been demonstrated; (b) the third degree interatrial blocks are less frequent but are strong markers of LAE and paroxysmal supraventricular tachyarrhythmias. Their presence has been considered a true arrhythmological syndrome. (C) 2012 Elsevier Inc. All rights reserved.
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