[Rinshō ketsueki] The Japanese journal of clinical hematology
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Recent progress in the development of novel therapeutic agents has remarkably improved the treatment outcome for multiple myeloma (MM). Proteasome inhibitors such as bortezomib, carfilzomib, and ixazomib; immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide, and pomalidomide; the histone deacetylase (HDAC) inhibitor panobinostat; and the monoclonal antibody, elotuzumab, have all been approved in Japan, although only bortezomib and lenalidomide have been approved for initial therapy. ⋯ These novel agents provide us with wider therapeutic options for relapsed or refractory patients. Consequently, treatment paradigms for MM continue to rapidly evolve, and it is important to select the optimal treatment strategy for each patient.
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Inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders characterized by bone marrow failure, congenital anomalies, and an increased risk of malignancies. Diagnosis is often difficult due to the wide variety of clinical expressions. ⋯ Recently, Japanese groups have identified novel causative genes for DBA, FA and congenital thrombocytopenia by applying whole exome-sequencing. In this review, we will highlight recent studies on DBA, FA and CSA in Japan, which have employed next-generation sequencing technologies to elucidate the genetic etiology of IBMFS.
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Case Reports
Successful rituximab treatment in an elderly patient with recurrent thrombotic thrombocytopenic purpura.
An 81-year-old man presenting with fever, neurological symptoms, thrombocytopenia, and hemolytic anemia was diagnosed with acquired idiopathic thrombotic thrombocytopenic purpura (TTP). His disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity was <1% and the ADAMTS13 inhibitor titer was 3.2 BU/ml. He received plasma exchange and steroid administration until remission was achieved. ⋯ No severe side effects related to rituximab occurred. Although rituximab has not been approved for TTP in Japan, we report the efficacy and safety of rituximab in an elderly patient with recurrent TTP. We suggest that rituximab therapy should be started as soon as possible for recurrent TTP in patients with high titers of ADAMTS13 inhibitor.
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Serious issues in current hemostatic treatment of hemophilia A are the requirement for frequent intravenous administrations of factor (F) VIII, FVIII inhibitor development, and hemostatic treatment for patients with this inhibitor. For the purpose of overcoming these challenges, the FVIIIa-substituting bispecific antibody against FIXa/FX (ACE910, INN emicizumab) was produced. Emicizumab demonstrated marked hemostatic effects on both ongoing and spontaneous joint bleeding in the acquired hemophilia A primate model. ⋯ The t1/2 was approximately 30 days, and bleeding events were significantly decreased by weekly subcutaneous administration in severe hemophilia A patients, independently of the presence of the inhibitor. Currently, the phase 1/2 extension study is ongoing. We anticipate that emicizumab will show the benefits of prophylactic efficacy with subcutaneous administration at a much lower frequency.
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Chimeric antigen receptor (CAR) is the generic name for synthetic T cell receptors redirected to tumor-associated antigens. Most CARs consist of an ectodomain (scFv or ligand), a hinge region, a transmembrane domain, and signaling endodomains derived from one or two co-stimulatory molecules (CD28, 4-1BB, etc) and from a CD3-ζ chain. CD19-targeted CAR T cell therapy has achieved major success in the treatment of B cell malignancies. ⋯ CD19 CAR T cell therapy from allogeneic donors including third party donors is a potential option for B-cell malignancies. CAR T cell therapies for myeloma, acute myeloid leukemia, and T-cell leukemia are still under development. Our group is currently preparing a phase I study of CD19 CAR T cell therapy in pediatric and young adult patients with ALL using a non-viral gene transfer method, the piggyBac-transposon system.