Expert review of hematology
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Brentuximab vedotin (BV) is a potent anti-CD30 antibody drug conjugate (ADC) that has been approved in relapsed or refractory Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT) and anaplastic large-cell lymphoma (ALCL). Beyond these consolidated indications, BV has been tested in a number of different settings with promising results, leading for example to the recent approval as a consolidation after ASCT in high-risk HL patients. ⋯ Main emerging areas of clinical investigation of BV include the use as a single-agent or in combination with bendamustine in first-salvage therapy of HL (bridge to ASCT), in the frontline setting in combination with AVD chemotherapy in HL and with CHP in ALCL, in relapsed or refractory cutaneous T-cell lymphomas and finally in diffuse large B-cell lymphomas (DLBCL) expressing CD30. Moreover, many new ADCs are currently under clinical evaluation, as for example the anti-CD79A polatuzumab vedotin in DLBCL. Expert commentary: In few years BV changed the therapeutic scenario of relapsed or refractory HL and ALCL and is rapidly moving toward first-line approval in combination with standard chemotherapy if ongoing randomized trials will demonstrate improved results. Combination strategies with bendamustine in first-salvage HL and with R-CHP in first-line DLBCL appear very promising.
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Recent developments in immunotherapy are improving treatment results of B-precursor acute lymphoblastic leukemia. This advancement is promoted by new monoclonal antibodies such as inotuzumab ozogamicin, ofatumumab and blinatumomab, by rituximab, and by genetically engineered chimeric antigen receptor-modified T-cells. ⋯ Beside the encouraging results in relapsed/refractory disease, these agents may open a totally new era in the frontline management of this illness, redefining treatment standards and options for different risk subsets and placing the achievement of a molecular remission at the forefront of treatment objectives. The ever increasing importance of modern immunotherapy in improving treatment design and therapeutic outcome is reviewed.
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Neutropenias (NPs), being acute and often transient, or chronic, range from life-threatening conditions with very low absolute neutrophil blood counts (ANC) to disorders characterized by only mild NP and of no obvious significance for health. Many are caused by genetic variations/mutations, e.g. the benign familial NP and the chronic severe NPs (e.g. Kostmann disease). ⋯ Many of the mild-to-moderate NPs are signs of underlying disorders that need specialized treatments (e.g. HIV, hepatitis, autoimmune disorders, the large granular lymphocyte syndrome). We provide here means for the evaluation of a previously unknown NP, suggest a triage and treatments.
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Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. The molecule is a recombinant protein analog of factor Xa that binds to Factor Xa inhibitors and antithrombin:LMWH complex but does not trigger prothrombotic activity. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. Further trials are underway to examine its safety and efficacy in the population of patients experiencing FXa inhibitor-related bleeding.
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Since affecting hemostasis, all the anticoagulant drugs carry a risk of bleeding. Minor bleeds may be managed without the need to reverse the anticoagulant effect, which is instead a key step to ensure efficacious hemostasis in major and life-threatening bleeding. Drug withdrawal applies to all anticoagulants. ⋯ For vitamin K antagonists-induced major bleeding, rapid reversal with prothrombin complex concentrates (PCC) or plasma and intravenous vitamin K to confer lasting correction are recommended. PCC, activated PCC and rFVIIa are suggested for major bleeding related to new direct oral anticoagulants (DOAC), despite proper studies are lacking. Premarketing studies are ongoing on new antidotes (idarucizumab, andexanet, aripazine), which appear to be suitable for the treatment of DOAC-induced life-threatening hemorrhage.