Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, with an incidence that increases with age, and a generally poor prognosis. The disease is clinically and genetically heterogeneous, and recent advances have improved our understanding of the cytogenetic abnormalities and molecular mutations, aiding in prognostication and risk stratification. Until recently, however, therapeutic options were mostly limited to cytotoxic chemotherapy. Since 2017, there has been an explosion of newly approved treatment options both nationally and internationally, with the majority of new drugs targeting specific gene mutations and/or pivotal cell survival pathways. In this review article, we will discuss these new agents approved for the treatment of AML within the last 2 years, and will outline the mechanistic features and clinical trials that led to their approvals.
Essentials
Delayed‐onset heparin‐induced thrombocytopenia can lead to severe thrombocytopenia in the setting of recent major vascular surgery.Intravenous immunoglobulin (IVIG) can be used as a supplementary treatment when platelet count fails to improve with conventional treatment.When platelet counts are severely low, benefits of using IVIG can outweigh the risks of thromboembolic events.
Delayed onset heparin induced thrombocytopenia (HIT), is characterized by a late nadir due to persistent platelet‐activating IgG antibodies. It typically begins or worsens 5 or more days after heparin is discontinued with complications such as thrombosis up to 3 weeks after exposure to heparin.1–3 In 50% of cases, the platelet count can decrease to very low numbers (<20 000/μL), which is not usual for typical HIT. Here we report 2 cases of post‐operative delayed onset HIT manifesting as severe thrombocytopenia that persisted despite cessation of heparin and initiation of argatroban. Key Clinical Question: Is intravenous immunoglulin beneficial in severe refractory delayed‐onset HIT?
Older age and poor performance status lead to worse outcomes in acute myeloid leukemia (AML) patients. Hypoalbuminemia is a negative predictor of morbidity and mortality in several malignancies. We evaluated the relationship between baseline serum albumin levels on treatment‐related complications, as well as short‐term mortality and overall survival (OS) in 756 newly diagnosed AML patients. We conducted a retrospective multicenter study to examine treatment‐related complications and OS according to pretreatment serum albumin levels: normal albumin ≥3.5 g/dl, marked hypoalbuminemia <2.5 g/dl, and hypoalbuminemia 2.5–3.4 g/dl. In an adjusted multivariate analysis, a lower baseline albumin was independently associated with a higher number of grade ≥3 complications when adjusting for age, secondary AML, sex and intensive treatment. When comparing normal to markedly low albumin levels, the estimated mean number of complications increases by a factor of 1.35. Patients who had a normal baseline albumin had a 30 day‐mortality rate of 4.8%, which was significantly lower compared with patients with hypoalbuminemia (16.5%) and marked hypoalbuminemia (33.9%; p < 0.01). Similarly, 60‐day mortality rate was significantly higher in the hypoalbuminemia group (24.0%) and marked hypoalbuminemia group (45%) compared with normal albumin group (8.3%; p < 0.01). Patients with lower baseline albumin levels have increased treatment‐related morbidity and mortality, suggesting that pre‐treatment serum albumin is an important independent prognostic marker.
Acute myeloid leukemia (AML) is an aggressive malignancy characterized by clonal proliferation of neoplastic immature precursor cells. AML impacts older adults and has a poor prognosis. Despite recent advances in treatment, AML is complex, with both genetic and epigenetic aberrations in the malignant clone and elaborate interactions with its microenvironment. We are now able to stratify patients on the basis of specific clinical and molecular features in order to optimize individual treatment strategies. However, our understanding of the complex nature of these molecular abnormalities continues to expand the defining characteristics of high-risk mutations. In this review, we focus on genetic and microenvironmental factors in adverse risk AML that play critical roles in leukemogenesis, including those not described in an European LeukemiaNet adverse risk group, and describe therapies that are currently in the clinical arena, either approved or under development.
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