Deutsche medizinische Wochenschrift
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Dtsch. Med. Wochenschr. · Apr 2023
Review[Transplantation/cellular therapy in acute myeloid leukemia - Who, When, Why and How?].
To date allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective immunotherapeutic approach for the treatment of acute myeloid leukemia (AML). It involves the transplantation of blood stem cells from a healthy donor into a patient, with the goal of using the donor's immune system to recognize and attack cancer cells (Graft-versus-leukemia effect). Thereby, allo-HSCT is more efficient than chemotherapy alone, as it combines high dose chemotherapy +/- irradiation with immunotherapy establishing a long-term control of leukemic cells while allowing reconstitution of a healthy donor hematopoiesis and a new immune system. ⋯ While allo-HSCT is currently the most established form of immunotherapy in the treatment of AML, other approaches that use the immune system to fight cancer are being researched. These may include immunomodulatory drugs or cell therapies such as CAR-T cells, which stimulate the immune system to attack cancer cells. Even if this does not yet play a role in current standard therapy, as our understanding of the immune system and its role in cancer grows, it is likely that targeted immunotherapies will become increasingly important in the treatment of AML The following article gives you an overview of allo-HSCT in AML patients and the current developments.
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Lipoprotein apheresis (LA) is usually a last resort in cardiovascular high-risk patients in the context of secondary prevention after lifestyle measures and maximal pharmacotherapy have failed to prevent the occurrence of new atherosclerotic cardiovascular events (ASCVDE) or to achieve the internationally accepted target values for LDL cholesterol (LDL-C). Patients with homozygous familial hypercholesterolemia (hoFH), in whom myocardial infarctions can occur even in children < 10 years of age without adequate therapy, often owe their survival to LA (used here in primary prevention). Severe hypercholesterolemia (HCH) can often be well controlled with modern potent lipid-lowering agents, including PCSK9 approaches, so that the need for LA has decreased here over the years. ⋯ This had been requested by the G-BA in 2008, and a corresponding concept was designed but not accepted by the ethics committee. In addition to the highly effective reduction of atherogenic lipoproteins, many discussed pleiotropic effects of LA itself, the medical rounds and motivating discussions also with the nursing staff, which take place within the weekly LA, certainly contribute to the success of the therapy (steady adjustment of all cardiovascular risk factors, lifestyle measures including smoking cessation, adherence of medication intake). This review article summarizes and discusses the study situation, clinical practical experience as well as the future of LA against the background of the currently rapid development of new pharmacotherapies.
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Dtsch. Med. Wochenschr. · Apr 2023
Review[Clonal hematopoiesis of undetermined potential (CHIP) and clonal cytopenia of unknown significance (CCUS) - Consequences for the clinic].
Clonal hematopoiesis of indeterminate potential (CHIP) refers to the outgrowth of blood cells from a hematopoietic stem cell (HSC) clone that acquired one or more somatic mutations, leading to a growth advantage compared to wild type HSCs. In the last years this age-associated phenomenon has been extensively studied, and several cohort studies found association between CH and age-related diseases, esp. leukaemia and cardiovascular disease. ⋯ In this year, CHIP and CCUS have been included in the updated WHO classification of hematolymphoid tumours. We review the current understanding of the emergence of CHIP, diagnostics, association with other diseases, and potential therapeutic interventions.
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Dtsch. Med. Wochenschr. · Apr 2023
ReviewHypoxic, anemic and cardiac hypoxemia: When does tissue hypoxia begin?
In case of hypoxemia, the oxygen content is often still in the lower normal range, so that there is no hypoxia in the tissue. If the hypoxia-threshold is reached in the tissue in hypoxic, anemic and also cardiac-related hypoxemia, identical counterregulations occur in the cell metabolism, regardless of the cause of hypoxemia. In clinical practice, this pathophysiologic fact is sometimes ignored, although depending on the cause of hypoxemia, assessment and therapy vary widely. ⋯ During the corona pandemic, misinterpretations of pathophysiology have become evident and may have led to unnecessary intubations. However, there is no evidence for the treatment of hypoxic hypoxia with ventilation. This review addresses the pathophysiology of the different types of hypoxia focusing on the problems associated with intubation and ventilation in the intensive care unit.
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While the "7+3" regimen of cytarabine + anthracycline has been the backbone of acute myeloid leukemia (AML) treatment for four decades, several novel drugs have been approved in the past five years. Despite these promising novel therapeutic options, treatment of AML remains challenging, given the biologically heterogenous character of the disease. ⋯ The treatment algorithm is based on patient-related and disease-specific factors, such as patient age and fitness as well as AML molecular profile. Younger patients considered fit for intensive chemotherapy receive 1-2 courses of induction therapy ("7+3" regimen, eg. cytarabine/daunorubicin, or CPX-351 for patients with myelodysplasia-related AML or therapy-related AML). For CD33+ patients or those with evidence of an FLT3 mutation "7+3" in combination with Gemtuzumab-Ozogamicin (GO) or Midostaurin is recommended, respectively. For consolidation, patients receive either high-dose chemotherapy (± GO/± Midostaurin) or undergo allogeneic hematopoietic cell transplantation (HCT), based on ELN risk stratification. In some cases, maintenance therapy with oral azacytidine or FLT3 inhibitor is indicated. Patients experiencing relapse should receive chemotherapy-based re-induction therapy or, in case of an FLT3 mutation, Gilteritinib and subsequently undergo allogeneic HCT. For older patients or those considered unfit for intensive therapy, azacytidine in combination with Venetoclax is a promising novel treatment strategy. Although not yet approved by the European Medical Agency (EMA), for patients with IDH1IDH1 or IDH2 mutations treatment with the IDH1 and IDH2 inhibitors Ivosidenib and Enasidenib should be considered.