Minerva medica
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Mutation within the FMS-like tyrosine kinase 3 (FLT3) gene are one of the most frequent genetic alterations in acute myeloid leukemia. A high mutation fraction of FLT3-ITD molecules on the surface of leukemia cells is associated with short remissions and overall adverse outcomes in AML. ⋯ We enumerate the practical issues faced in the use of midostaurin like antifungal prophylaxis, dosage of concomitant chemotherapy agents as well as available data on sequencing of the FLT3 inhibitors. Lastly, we provide our perspective of the future directions for FLT3 inhibition especially midostaurin, the underlying resistance mechanisms and the need for standardization of the FLT3 tests.
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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy, characterized by poor prognosis if treated with conventional therapy. Allogenic hematologic stem cell transplant can improve survival and can be curative, but it is available in a small percentage of patients given that the median age at diagnosis is 70 years. In this scenario it is assumed that only the development of precision medicine-driven therapy will change BPDCN patient prognosis. ⋯ Therefore, to prevent the onset of severe CLS is recommended to reserve tagraxofusp for patients with preserved hepatic and cardiac functions, and to strictly observe serum albumin level. Further studies are required to resolve many several unanswered questions about tagraxofusp. In this review, we will resume and discuss pharmacological characteristic of tagraxofusp, results of clinical trials leading to its approval by FDA in 2018 and future perspectives about its use in BPDCN and other hematological malignancies.
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Baseline cytogenetic/genetic features have been widely recognized to play a critical prognostic role in acute myeloid leukemia (AML) and have proven useful in designing risk-adapted treatment strategies. Nevertheless, to improve further the outcome of AML patients we are still in need of accurate methods to explore the quality of response and to adequately discriminate patients who are likely to relapse over time from those who are in deep and stable remission. ⋯ Detection of MRD relies on highly sensitive techniques, such as quantitative polymerase chain reaction and multiparametric flow cytometry, which, due to their levels of specificity and sensitivity, are increasingly included in the decision-making process of AML treatment. In the present manuscript, we will review the current techniques of MRD investigation and their clinical contribution to AML management.