Treatment discontinuation following low-dose TKIs in 248 chronic myeloid leukemia patients: Updated results from a campus CML real-life study

TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate

"Imeneo sotto il platano": un motivo bucolico in Claudiano (carm. min. 25)

Nelle scene del sonno di Venere e del dialogo tra Venere e Imeneo, l’Epitalamio per Palladio e Celerina di Claudiano (carm. min. 25) si distingue dalla tradizione epitalamica per l'atmosfera bucolica, evocata da una serie di riferimenti tematici e formali al genere letterario. Le parole di Venere e Imeneo sembrano comunicare un articolata riflessione dell'autore sulla poetica espressa nell'epitalamio: Imeneo fungerebbe da portavoce di Claudiano, rivendicando la possibilità per il poeta di adattare i toni bucolici alle esigenze encomiastiche del carme d occasione. È possibile che lo sviluppo narrativo dell'episodio di Imeneo sia stato suggerito a Claudiano dall'inno cletico del carme 61 di Catullo. Claudiano potrebbe aver sfruttato le possibilità offerte dalla forma dell'epitalamio epico per fare dell'invocazione a Imeneo un episodio organico al racconto.In the scenes of Venus’ sleep and of the dialogue between Venus and Hymenaeus, Claudian's Epithalamium for Palladius and Celerina (carm. min. 25) stands out from the epithalamic tradition for its bucolic atmosphere, which is summoned by several thematic and stylistic references to the literary genre. The words of Venus and Hymenaeus seem to communicate an articulate reflection of the author on the poetics of the epithalamium: Hymenaeus may be acting as spokesman for Claudian, claiming the possibility for the poet to adapt the bucolic modes to the encomiastic needs of the occasional poem. The narrative development of Hymenaeus’ episode might have been suggested to Claudian by the cletic hymn of Catullus 61. Claudian seems to have taken advantage of the possibilities offered by the form of the epic epithalamium in order to make the invocation to Hymenaeus an episode incorporated in the narrative

Critical review of clinical data and expert-based recommendations for the use of bosutinib in the treatment of chronic myeloid leukemia

Adverse event; Chronic myeloid leukemia; Tyrosine kinase inhibitorsEvento adverso; Leucemia mieloide crónica; Inhibidores de la tirosina quinasaEsdeveniment advers; Leucèmia mieloide crònica; Inhibidors de la tirosina cinasaChronic myeloid leukemia (CML), characterized by the presence of the BCR::ABL1 fusion gene, has undergone a transformative shift with the introduction of tyrosine kinase inhibitors (TKIs). The current availability of six different TKIs (imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and asciminib) in clinical practice makes it important to know their efficacy and toxicity profile for treatment optimization. This review examines the latest insights regarding the use of bosutinib in CML treatment. Clinical trials have demonstrated the effectiveness of bosutinib, positioning it as a first-line treatment that can induce sustained molecular responses. Importantly, it can also be effective in patients who have experienced treatment failure or intolerance with prior TKIs, revealing the potential of bosutinib also in second- and later-line settings. Even in the advanced phase of CML, bosutinib has demonstrated its capacity to achieve molecular responses, expanding its usefulness. Real-world evidence studies echo these findings, emphasizing bosutinib’s effectiveness in achieving deep molecular responses, maintaining remissions, and serving as an alternative for patients intolerant or resistant to other TKIs as a second-line therapy. Notably, one of the greatest strengths of bosutinib is its favorable safety profile, in particular the low incidence of vascular complications with its use, which is undoubtedly a comparative advantage over other TKIs. In summary, the latest research highlights the versatility of bosutinib in CML treatment and underscores its pivotal role in optimizing patient management in challenging cases. Continuing research and investigation will further establish bosutinib’s place in the evolving landscape of CML therapy, offering an alternative for CML patients across different treatment stages

Pignus ou le mutisme des dictionnaires médiolatins sur une évolution sémantique

Some medieval Latin words lead us to reflect on the relationship between medieval dictionaries of Latin and medieval Latin itself. It would appear that such dictionaries should be used with care, bearing in mind that they are not intended to record the state of the language but rather to establish a word's historical and semantic foundation. By studying pignus and other examples, this article aims to specify the conditions under which these dictionaries, compiled by actual users of medieval Latin, may inform us less about the perception of the language as an object of study and more about the object itself, medieval Latin. RésuméCertains mots du vocabulaire médiolatin nous amènent à réfléchir sur les rapports entre les dictionnaires médiévaux du latin et le latin médiéval. Il semble que ces dictionnaires soient à manier avec prudence, en se souvenant qu'ils ne sont pas là pour enregistrer un état de la langue mais plutôt pour donner à un mot une assise historique et sémantique qui lui manque. À partir d'une étude du terme pignus et de certains autres exemples, cet article veut cerner dans quelles conditions ces dictionnaires réalisés par des utilisateurs du latin médiéval eux-mêmes peuvent nous renseigner non pas tant sur la perception de la langue comme objet d'étude, mais plutôt sur l'objet lui-même, le latin médiéval

Treatment discontinuation following low-dose TKIs in 248 chronic myeloid leukemia patients: Updated results from a campus CML real-life study

TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate

Estudos Organizacionais e Estudos Curriculares: uma agenda de convergência entre o passado e o futuro de campos paralelos

O artigo tem como objetivo analisar as trajetórias dos Estudos Organizacionais e dos Estudos Curriculares ao longo do século XX e início do século XXI, ressaltando as suas simetrias e convergências teóricas. Como as organizações podem variar infinitamente no tempo e no espaço, os currículos variam de instituição a instituição, de um curso a outro. Portanto, em ambas trajetórias, os estudos acumularam conhecimentos sobre as organizações e os currículos como construções sociais. Dessa forma, organizações e currículos são reflexos de práticas sociais. A partir das convergências encontradas e sua análise, será proposta uma agenda de pesquisas futuras que contemple os dois campos de estudo, de forma convergente, tratando estudos organizacionais como eixo estruturante de cursos de administração, o que é especialmente importante momento em que se rediscute os desenhos institucionais do ensino no Brasil, no cenário reformista dos projetos governamentais e como reflexo das mudanças que vive a universidade no mundo, em tempos de riscos, incertezas e reconstrução paradigmática