[Rinsho ketsueki] The Japanese journal of clinical hematology最新文献

Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection. The prothrombotic/antithrombotic balance within blood vessels can be shifted toward prothrombotic in infectious diseases. This is a physiological defense mechanism intended to contain the disturbance in peripheral tissues and prevent it from reaching the central systems. However, in severe infections where this response does not remain localized, extensive ischemic organ damage leads to sepsis-associated disseminated intravascular coagulation (DIC) with multiple organ failure. In such cases, anticoagulation therapy can alleviate ischemic organ damage. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2024 and the Clinical Practice Guidelines for Management of DIC in Japan 2024 recommend antithrombin or recombinant thrombomodulin for sepsis-associated DIC. Further discussion is needed to determine the optimal candidates and methods for treatment.

Patients with X-linked agammaglobulinemia (XLA) cannot produce antibodies. In this study, we investigated antibodies against SARS-CoV-2 in a man in his 40s with XLA who had no history of COVID-19 or vaccination against COVID-19. Even though his close contact mother contracted SARS-CoV-2, he had never been infected. We measured N-IgG and S-IgG antibodies, as well as neutralizing activity. Serum antibody titers were higher after administration of immunoglobulin, and the antibody titers of immunoglobulin preparations were high as well. Our data revealed that regular administration of immunoglobulins sufficiently increases virus-specific neutralizing antibody activity in patients with XLA.

Conventional treatments for hemophilia have focused on replacing the missing coagulation factor, but a new treatment concept called rebalancing therapy has recently emerged. Rebalancing therapy corrects bleeding tendency by adjusting the balance between coagulation and anticoagulation, and specifically targets TFPI, AT and APC. The anti-TFPI agents concizumab and marstacimab are administered subcutaneously and have been approved for use in Japan. They are monoclonal antibodies that target the K2 domain of TFPI, and improve hemostatic function by inhibiting the binding of TFPI to FXa and TF/FVIIa complexes. The siRNA drug fitusiran is used as an anti-AT agent that reduces the synthesis of AT, and SerpinPC as an anti-APC agent that specifically inhibits APC. This article will outline the concept of rebalancing therapy and the results of clinical trials, as well as precautions and potential issues during treatment.

Acute myeloid leukemia (AML) is becoming more prevalent as the Japanese population ages, highlighting the growing importance of individualized treatment based on age, comorbidities, and genetic abnormalities. This review outlines the significant transformation in AML management after the introduction of azacitidine plus venetoclax, FLT3 inhibitors, and CPX-351. It also discusses HEM-SIGHT, a next-generation sequencing panel developed in Japan that became covered by Japanese national health insurance in 2025, enabling a molecularly stratified approach to diagnosis. Despite advances in treatment, several subtypes including TP53-mutated and MECOM-overexpressing AML remain highly refractory, even with allogeneic stem cell transplantation and targeted therapies. These high-risk entities pose ongoing therapeutic challenges. The current paradigm in AML treatment has shifted toward strategic personalization, encompassing molecular abnormality identification, measurable residual disease assessment, and treatment adaptation based on these findings. To achieve wider adoption of precision medicine in clinical practice, Japan must continue strengthening its diagnostic systems, streamlining genomic testing in routine practice, and integrating these strategies with novel therapeutic development.

Genetically modified T cell therapies using a chimeric antigen receptor (CAR) or a modified T cell receptor (TCR) have emerged as an attractive approach to cancer treatment, especially for hematological malignancies, and are becoming an indispensable therapeutic option in clinical practice. CAR- and TCR-T cell development continues to face many challenges, including relapsed/refractory disease, adverse events, manufacturing failures, and cost. Nevertheless, several significant achievements have been made, including favorable clinical responses in CAR-T cell trials and the first approval of a TCR-T cell product for synovial sarcoma by the FDA. This review article will describe the current state and future outlook of gene modified T cell therapy development, and will briefly discuss the drug discovery ecosystem for cell therapy platforms, with a particular focus on Japan.

Immune thrombocytopenia (ITP) is defined as acquired thrombocytopenia with a platelet count of less than 100,000/ml and is caused by increased platelet destruction and decreased platelet production by immune mechanisms. ITP is essentially a diagnosis of exclusion, made when other thrombocytopenic diseases are ruled out. The goal of ITP treatment is not to return platelet counts to normal, but to improve bleeding symptoms and prevent serious bleeding. Indications for treatment should be based on platelet counts, severity of bleeding symptoms, patient characteristics, and lifestyle.

A 75-year-old man diagnosed with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia did not respond to standard induction chemotherapy, but was successfully treated with inotuzumab ozogamicin (InO). Although ascites developed after three cycles of InO, the clinical criteria for sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD) were not met due to the absence of jaundice and hepatomegaly. However, an increase in the HokUS-6 score from 1 to 4 led us to discontinue InO, considering the risk of SOS/VOD. Three months later, the ascites recurred and a transjugular liver biopsy (TJLB) was performed, resulting in a pathological diagnosis of SOS/VOD. Although the symptoms associated with SOS/VOD temporarily improved with recombinant thrombomodulin and other supportive care, the ascites returned 1 month later along with jaundice. The patient died of liver failure progression that showed no improvement with defibrotide. Pathological examination at autopsy revealed enlarged endothelial cells and fibrosis of the central hepatic vein. In cases where the diagnosis of SOS/VOD is inconclusive based on clinical findings and HokUS scores, TJLB may facilitate earlier diagnosis and effective therapeutic decision-making for SOS/VOD.