Safe discontinuation of nilotinib in a patient with chronic myeloid leukemia: a case report

Case presentation. We report the case of a 64-year-old Caucasian man diagnosed with chronic-phase chronic myeloid leukemia in April 2005. After 4 years of treatment with imatinib, he became intolerant to the drug and was switched to nilotinib. Two years later, he decided to stop nilotinib. Undetectable molecular response persisted for 30 months after discontinuation of the drug. Introduction. Although there is a considerable amount of data in the literature on safe discontinuation of first-generation tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia, little is known about discontinuation of second-generation tyrosine kinase inhibitor therapy. Most previous studies have been focused on dasatinib, and the few cases of nilotinib withdrawal that have been reported had a median follow-up of 12 months. To the best of our knowledge, the present report is the first to describe nilotinib withdrawal with 30 months of follow-up. Conclusion: Our present case suggests that nilotinib withdrawal is safe for patients with chronic myeloid leukemia who achieve a stable undetectable molecular response. Our patient was homozygous for killer immunoglobulin-like receptor haplotype A, previously reported to be a promising immunogenetic marker for undetectable molecular response. We recommend additional studies to investigate patient immunogenetic profiles and their potential role in complete response to therap

Bone marrow homing and engraftment defects of human hematopoietic stem and progenitor cells

Homing of hematopoietic stem cells (HSC) to their microenvironment niches in the bone marrow is a complex process with a critical role in repopulation of the bone marrow after transplantation. This active process allows for migration of HSC from peripheral blood and their successful anchoring in bone marrow before proliferation. The process of engraftment starts with the onset of proliferation and must, therefore, be functionally dissociated from the former process. In this overview, we analyze the characteristics of stem cells (SCs) with particular emphasis on their plasticity and ability to find their way home to the bone marrow. We also address the problem of graft failure which remains a significant contributor to morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Within this context, we discuss non-malignant and malignant hematological disorders treated with reduced-intensity conditioning regimens or grafts from human leukocyte antigen (HLA)-mismatched donor

Antonio Cossu, uno scrittore olivettiano in Sardegna

Antonio Cossu, uno scrittore olivettiano in Sardegna &nbsp

Stampante Raise 3D Pro 3 Plus

Panoramica generale, setup ed esempi di stampa della stampante Raise 3D Pro3 Plu

IFNα-mediated suppression of JCV is mTOR pathway dependend

The severe demyelinating disease progressive multifocal leukoencephalopathy (PML) is caused by the neurotropic polyomavirus JC (JCV), which replicates in oligodendrocytes and astrocytes in the brain. Infection by JCV is very common and is widespread worldwide, but PML occurs very rarely. Primary infection occurs early in life, usually in childhood, but the virus is contained by the action of immune system and subsequently persists asymptomatically. Initiation of PML occurs occasionally under conditions of immune dysfunction and results from the reactivation of persistent virus from an inactivate state to replicate lytically. Our earlier studies suggest that reactivation occurs within glial cells due to the action of cytokines, e.g. TNF-alpha, stimulating viral gene expression. In this study, we have now examined the cytokine interferon-alpha (IFN-alpha), which, in contrast, has a negative effect on JCV gene expression and replication. IFN-alpha and IFN-beta inhibited the replication of JCV in primary human fetal astrocytes and reduced transcription by JCV promoter reporter constructs in oligodendroglioma cells. We found that IFN-α treatment of glial cells induced expression of STAT1 and caused STAT1 phosphorylation and translocation to the nucleus. Other downstream signaling events were also examined including PI3K/Akt and mTOR and inhibition of PI3K with LY294002 was found to enhance JCV replication while rapamycin inhibition of mTOR affected STAT1 translocation to the nucleus. We conclude that pathways downstream of IFN-alpha negatively regulate JCV gene expression and replication and this may present new therapeutic opportunities for PML

Esercizi deleddiani degli esordi

.La intervención del Prof. Duilio Caocci de la Universidad de Cagliari, tuvo lugar durante unas jornadas organizadas por el Dr. Giovanni Caprara de la Universidad de Málaga. Las jornadas tuvieron lugar en Málaga, los días 13 y 14 de noviembre de 2014, con motivo de la presentación del Taller de Lectura organizado por Culturitalia y bajo el patrocinio de: Universidad de Málaga, Istituto Italiano di Cultura (Madrid), Centro Andaluz de las Letras (Junta de Andalucía), Dante Alighieri - Málaga y Escuela Oficial de Idiomas (Málaga).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Arterial Hypertension and Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Systematic Review and Meta-Analysis

Background: Off-target effects in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) are associated with cardiovascular toxicity. Hypertension represents an important cardiovascular complication and, if not appropriately managed, can contribute to developing thrombotic events. Third-generation TKI ponatinib is associated with hypertension development, and its use is more restricted than in the past. Few data are reported for second-generation TKI, nilotinib, dasatinib, and bosutinib. The aim of this article was to evaluate with a systematic review and meta-analysis the real incidence of hypertension in CML patients treated with second- or third-generation TKI. Methods: The PubMed database, Web of Science, Scopus, and ClinicalTrials.gov were systematically searched for studies published between January 1, 2000, and January 30, 2021; the following terms were entered in the database queries: Cardiovascular, Chronic Myeloid Leukemia, CML, Tyrosine kinases inhibitor, TKI, and Hypertension. The study was carried out according to the Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) statement. Results: A pooled analysis of hypertension incidence was 10% for all new-generation TKI, with an even higher prevalence with ponatinib (17%). The comparison with the first-generation imatinib confirmed that nilotinib was associated with a significantly increased risk of hypertension (RR 2; 95% CI; 1.39-2.88, I2=0%, z=3.73, p=0.0002). The greatest risk was found with ponatinib (RR 9.21; 95% CI; 2.86-29.66, z=3.72, p=0.0002). Conclusion: Hypertension is a common cardiovascular complication in CML patients treated with second- or third-generation TKI

Lapide funebre a Teresa Olga Tambelli a Cagliari (1964)

Scheda relativa alla lapide funebre a Teresa Olga Tambelli a Cagliari (1964