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Therefore, it is expected that combination therapy with anti-CD38 antibodies and IMiDs may enhance anti-tumor immunity. Furthermore, chimeric antigen receptor (CAR) T cell therapy, antibody drug conjugates (ADC), and bispecific antibodies (BsAbs) are in the process of their introduction to the clinic as novel immunotherapies for MM.It has been 20 years since the clinical introduction of rituximab, a monoclonal anti-CD20 antibody. Rituximab combination chemotherapy has substantially improved the prognosis of nearly all B-cell malignancies. Twenty years following the clinical introduction of rituximab, the era of molecular targeted agents and development of novel molecular targeted agents, including monoclonal antibody based on the molecular pathology, has been promoted. In recent years, CAR-T therapy and immune checkpoint inhibitors have been introduced in the clinical practice of malignant lymphoma. On the other hand, there are many histopathological subtypes that cannot directly receive the benefits of immunotherapy, and sufficient improvement in the prognosis of these subtypes is not seen. Therefore, further elucidation of molecular pathology and development of novel molecular targeted agents are crucial for the improvement of their prognosis. In this review, molecular targeted agents introduced into clinical practice in recent years, which revolutionized the treatment of malignant lymphoma, and molecular targeted agents expected to be introduced in clinical practice in the near future are discussed.Iron-deficiency anemia (IDA) is the most common form of anemia. It is treated through iron replacement therapy, with oral iron administration as the recommended first-line treatment. However, intravenous (IV) iron formulation is at timed used owing to adverse effects of oral iron administration such as gastrointestinal symptoms. Although saccharated ferric iron oxide had been the only available IV iron formulation in Japan for a long time, ferric carboxymaltose (FCM) has recently been approved. In this review, the characteristics, efficacy, and safety of FCM will be discussed mainly by introducing the results of three clinical trials for FCM conducted in Japan. More effective treatment for patients with IDA might be achieved through the introduction of FCM administration in clinical settings.Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disease whose main symptom is complement-mediated intravascular hemolysis as a result of the clonal expansion of hematopoietic stem cells having mutations in genes involved in glycosylphosphatidylinositol (GPI) anchor synthesis including PIGA. With the advent of a humanized anti-C5 monoclonal antibody (eculizumab), the inhibitory effect on hemolysis, improvement in its various complicating symptoms, and preventive effect on thrombus formation were observed. In addition, the QOL in patients with PNH was significantly improved. Subsequently, the technology of recycling antibodies (ravulizumab and crovalimab) significantly extended the treatment interval and improved convenience, although the poor improvement of anemia due to extravascular hemolysis has been a major issue in some patients. Several clinical trials using proximal complement inhibitors (C3, factor D, factor B) are being conducted to overcome this critical task. Not only efficacy but also safety and convenience will be evaluated, and the best therapeutic agent will be selected in the near future.Anemia is a significant complication of chronic kidney disease (CKD), caused by erythropoietin deficiency and reduced iron availability. Erythropoiesis-stimulating agents have been used with iron supplementation to treat anemia; however, they are associated with some problems. Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) is a promising new class of oral therapy for the treatment of anemia associated with CKD. HIF-PHI inhibits HIF-prolyl hydroxylase enzymes and results in the HIF-α accumulation, which leads to increased expression of HIF-responsive genes, including erythropoietin and vascular endothelial growth factor (VEGF). HIF stimulates endogenous erythropoietin production and also reduces circulating hepcidin concentrations, resulting in improved anemia. https://www.selleckchem.com/peptide/box5.html Many clinical trials demonstrate that HIF-PHI improves anemia in patients with CKD and on dialysis. In addition to treating anemia, HIF-PHI may have multiple potential effects. Several animal experiments show that HIF-PHI protects against ischemic kidney damage that progresses to CKD and also improves metabolic disorders and ameliorates cardiovascular complications. In contrast, malignant tumor and retinopathy should be carefully evaluated due to theoretical concerns that HIF stabilization may result in increased VEGF protein expression. Some adverse events such as shunt occlusion reported in large clinical trials also need attention and warrant further investigations.Aggressive NK cell leukemia (ANKL) is a rare leukemic form of mature NK cell neoplasms. ANKL presents a fulminant clinical course with a median overall survival (OS) of 2-3 months after diagnosis. Currently, allogeneic stem cell transplantation (allo-HSCT) is the only curative treatment for ANKL patients. Although a few recent reports have evaluated the efficacy of allo-HSCT for ANKL patients, detailed outcomes of allo-HSCT are obscure. We conducted a nationwide retrospective analysis of 59 ANKL patients who underwent first allo-HSCT between 1997 and 2016 in Japan. The median age was 37 years, and 68% were male. The 1- and 5-year OS were 33.9% and 27.3%, respectively; the 1-year cumulative incidence of relapse or progression was 55.5%. The OS was significantly better for patients with complete or partial responses as the time of allo-HSCT, which was equivalent to that for patients who experienced primary induction failure but achieved complete response after allo-HSCT. Patients who underwent cord blood transplantation had significantly better outcomes than those who underwent allo-HSCT from other sources. Therefore, our study demonstrates that allo-HSCT is a promising treatment that can provide a durable response in a subset of ANKL patients. A larger-scale study including unselected ANKL patients is warranted in the future.
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