Expert review of hematology
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Richter transformation (RT) represents an aggressive transformation of chronic lymphocytic leukemia (CLL), most commonly into diffuse large B cell lymphoma (DLBCL). It occurs in around 5% of patients with CLL. ⋯ This review will focus on the biology and treatment of RT. We also address the management of RT in the era of targeted therapies. Based on clonal relationship of large cell component to CLL, 2 distinct subtypes could be identified: clonally-related RT which carries a worse outcome, and clonally-unrelated RT where the outcomes are similar to de novo DLBCL. Aberrations of TP53, CDKN2A, MYC, and NOTCH1 are common in RT, many of which are acquired at the time of transformation. PET scan remains the imaging modality of choice for patients with suspected RT. It is important to perform a biopsy rather than fine needle aspiration (FNA) of the suspicious lesions, as FNA can lead to false negative results. Chemoimmunotherapy remains the treatment of choice, though the outcomes remain suboptimal. The median survival is less than 1 year. Novel therapies are needed for patients with RT. Expert commentary: RT remains an unmet medical need; the role of targeted therapies, including immunotherapy needs to be explored.
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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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Sickle cell anemia is one of the most common genetic blood disorders worldwide. Individuals with sickle cell disease (SCD) experience clinical manifestations such as chronic anemia, developmental delay, vaso-occlusive pain, acute chest syndrome, and neurological complications. ⋯ This review focuses on these challenges with particular emphasis on delayed menarche and vaso-occlusive pain episodes associated with menstruation, in addition to the evaluation and initial management of heavy menstrual bleeding for adolescents with SCD. We highlight research opportunities in this neglected area to help enhance the comprehensive care model for this population.
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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.