Expert review of hematology
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Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease. Deregulation of apoptosis is a major pathogenetic feature, and represents a therapeutic target. TP53 disrupted patients are categorized as high risk patients and are treated with novel target therapies. ⋯ Expert commentary: The availability of venetoclax represents a major advance in CLL treatment and offers new opportunities to further improve the results obtained until now by combining venetoclax with other agents. Venetoclax has achieved responses also in patients with TP53 disruption. These results strongly suggest that the mechanism by which venetoclax kills CLL cells might overcome a dysfunctional TP53 that is a major hallmark of chemorefractoriness to conventional antineoplastic agents.
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Immunotherapy is a promising modality of treatment of neoplastic diseases, including acute lymphoblastic leukemia (ALL). The CD19/CD3-bispecific T cell-engaging (BiTE®) monoclonal antibody blinatumomab can transiently bind cytotoxic T cells to CD19+ target B cells of ALL inducing their serial lysis. ⋯ Blinatumomab has a favorable safety profile, although reversible CNS events and cytokine release syndrome can occur. Ongoing trials in ALL incorporate blinatumomab in the first line therapy of BCP ALL in combination with chemotherapy, targeted therapies or other immunotherapies with the aim of increasing the depth of the remission and decreasing the probability of relapse.
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Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with inadequate treatment options. Approximately one-third of cases have a FLT3-ITD or FLT3-TKD mutation which leads to constitutive tyrosine kinase activation which contributes to leukemogenesis. The FLT3-ITD mutation is associated with a particularly poor prognosis. ⋯ It is also the first targeted therapy approved for AML. Future studies will focus on defining mechanisms of resistance to midostaurin as well as establishing the role of midostaurin in combination with hypomethylating agents and as maintenance therapy. Second generation, more potent and selective FLT3 inhibitors are also in development; these agents need to be compared to midostaurin.
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The number of atrial fibrillation (AF) patients requiring thrombo-prophylaxis with oral anticoagulation is greatly increasing. The introduction of non-vitamin K oral anticoagulants (NOACs) in addition to standard therapy with dose-adjusted warfarin has increased the therapeutic options for AF patients. Despite a generally better safety profile of the NOACs, the risk of major bleedings still persists, and the management of serious bleeding is a clinical challenge. ⋯ Expert commentary: Due to short half-life of NOACs compared to warfarin, discontinuation of drug, mechanical compression, and volume substitution are considered to be sufficient measures in most of bleeding cases. In case of life-threatening bleeding or urgent surgery, hemostasis can be achieved with non-specific reversal agents (prothrombin complex concentrates) in patients treated with factor Xa inhibitor until specific antidotes (andexanet α and ciraparantag) will receive approval. Thus far, idarucizumab has been the only reversal agent approved for dabigatran.
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Iron deficiency is a frequent comorbidity of chronic diseases such as inflammatory bowel disease that can severely impact the health and quality of life of affected individuals. It can exist as a silent condition and manifest in non-specific symptoms even in the absence of anemia. ⋯ Expert commentary: We invite international gastroenterological societies and associations to refine the practice guidelines and include iron deficiency as a potential morbidity associated with IBD in analogy to arthritis, uveitis or any other extra intestinal manifestations. There should a more unanimous agreement among different societies on the specific diagnostic cutoff values for C-reactive protein levels, serum ferritin, and transferrin saturation in order to differentiate iron deficiency anemia from anemia of chronic disease.