[Rinshō ketsueki] The Japanese journal of clinical hematology
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Immuno-checkpoint inhibitors are one of the most promising immunotherapies for various advanced cancers including hematologic malignancies. Recently, enhanced signaling of the PD-1/CTLA4 pathway has emerged as a critical mechanism by which tumors can escape the anti-tumor immune response. ⋯ Currently, several clinical trials including single agent or combination therapies for hematologic malignancies, such as Hodgkin lymphoma, B-cell lymphomas and multiple myeloma, are ongoing. The results of ongoing and future clinical trials may establish a new treatment paradigm for hematologic malignancies.
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The principle of hemophilia treatment is replacement therapy with factor VIII and factor IX concentrates. Recently, extended half-life factor VIII and factor IX concentrates have been developed. With these concentrates, improvements in patient QOL can be expected. ⋯ ACE910 (emicizumab) is a humanized bispecific antibody recognizing factor IXa and X mimicking factor VIII function. The half-life is reportedly 4-5 weeks and remarkably decreased annual bleeding rates have been achieved with subcutaneous weekly injections in the phase 1 clinical trial. Clinical trials of anti-antithrombin therapeutics based on siRNA (ALN-AT3) and anti-TFPI antibody are currently ongoing and the results are eagerly anticipated.
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Acquired bone marrow failure syndromes consist of aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH), and myelodysplastic syndromes (MDS). Clonal hematopoiesis is frequently observed in non-neoplastic disorders, aplastic anemia and PNH as well as a neoplastic phenotype, MDS. ⋯ Recent advancements in next generation sequencing technology have revealed a diverse clonal structure in these bone marrow failure syndromes, as well as in age-related clonal hematopoiesis in healthy people. In this review article, we describe gene mutations in bone marrow failure syndromes, together with those detected in healthy people.
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The inherited bone marrow failure syndromes (IBMFS) are rare disorders in which there is usually some form of bone marrow failure and typical changes in physical appearance, associated with a family history of the same disorder. Patients with IBMFS have a very high risk of developing myelodysplastic syndrome, acute myeloid leukemia, and solid tumors. ⋯ In this section, we describe physical and laboratory findings and management of the major IBMFS: Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, and Diamond Blackfan anemia. We also discuss their possible implications in the clinical features of Japanese patients.
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With improvement of survival owing to the recent implementation of new anti-myeloma (MM) agents, bone management will become more important for maintaining the quality of life (QoL) of patients. Bisphosphonates are currently the standard of care for MM-related bone disease. Zoledronic acid is recommended for newly diagnosed MM patients receiving front-line anti-MM treatment regardless of existing detectable bone lesions. ⋯ Bisphosphonates but not denosumab deposit in bone with a long half-life, which may make a difference in long-term efficacy as well as adverse effects. Clinical benefits of long-term anti-resorptive therapies after achieving a good response should be clarified, in order to avoid the emergence of severe complications. Impacts of new agents in combination with these anti-resorptive agents on bone metabolism have yet to be studied.