Notes

Intense and long-term outcomes of high-intensity interval training (HIIT) about postexercise intramuscular lipid metabolic rate throughout rodents.
Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) caused by ADAMTS13 deficiency. Although the name of TTP is well known, most hematologists find its diagnosis and treatment difficult because it is ultrarare. TTP is an acute-onset and fatal disorder. Approximately 90% of TTP patients die within 2 weeks of onset without proper medical treatment. Although most doctors may remember being taught the five TTP symptoms (fever, transient central nervous system symptoms, hemolytic anemia, thrombocytopenia, and kidney dysfunction) at medical school, only 7% of TTP patients present with all five symptoms. Thus, TTP must be suspected in patients with microangiopathic hemolytic anemia and thrombocytopenia, and plasma therapy must be initiated as soon as possible after ordering the ADAMTS13 test. In this article, I describe how to differentially diagnose TMA as well as the standard and the updated therapy, such as rituximab and caplacizumab, for TTP treatment.The treatment strategy of adult idiopathic thrombocytopenic purpura (ITP) in Japan had consisted of corticosteroids as the first-line option, splenectomy as the second-line option, and others as the third-line option, respectively, for a long time. However, thrombopoietin receptor agonists (TPO-RAs) have been widely adopted recently for corticosteroid-resistant ITP, and indications for rituximab have been extended to adult ITP in Japan, suggesting that ITP treatment is dramatically changing. In the "Reference guide for adult ITP treatments in Japan" revised in 2019, TPO-RAs and rituximab are equally recommended as second-line treatments alongside splenectomy. It is suggested to select from among the second-line treatments with careful consideration of not only their advantages and disadvantages but also aspects of the condition and situation of each patient such as any comorbidities or lifestyle factors. Moreover, since multiple effective therapeutic options are now available as second-line options, it is preferable to consider an early transition to second-line treatments for corticosteroid-refractory/dependent ITP patients.The treatment paradigm in multiple myeloma (MM) together with the introduction of novel agents have resulted in a considerably improved survival. However, the disease is still considered incurable. One of the factors of its recurrence was that acquired genomic events associated with the progression of MM lead to inter- and intrapatient clonal heterogeneities. Also, just like many other cancers, MM contains cancer stem cells, a rare subpopulation of MM cells that exhibit the capacity for self-renewal and differentiation, but also pronounced drug resistance. Furthermore, a growing body of evidence suggests the role of tumor microenvironment and anti-myeloma immune status in the progression and maintenance of MM. Despite much progress in MM pathology, there are still several issues left unsolved. In this review, we will discuss the recent advances in our understanding of the pathology of MM from the perspective of tumor cell-of-origin and how these advances can lead to more effective therapies targeting MM.Recent advances in novel therapeutic agents, such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, have markedly improved treatment outcomes in patients with multiple myeloma. The novel agent-based induction, followed by autologous transplantation, is considered as the standard treatment for transplant-eligible patients. Post-transplant consolidation and maintenance therapy can help maintain the subsequent response and further improve the treatment outcome in patients. Currently, there are several validated sensitive assays evaluating minimal residual disease (MRD), which have provided a means to quantitatively assess residual disease and accurately predict its prognosis in terms of progression-free and overall survival. Novel clinical studies that formally assess the effect of MRD negativity on clinical decision-making are ongoing. This session aims to provide an in-depth and comprehensive summary of the latest treatment strategy and MRD-based knowledge in newly diagnosed transplant-eligible patients with multiple myeloma.Novel drugs, such as proteasome inhibitors, immunomodulators, and antibody drugs, have been consistently developed, and several standard treatment regimens were approved for elderly patients with multiple myeloma who are ineligible for autologous transplantation. Meanwhile, the clinical characteristics of elderly patients are more diverse than those of younger patients in terms of various factors, such as cognitive, mental, or social functions as well as physical or organ functions. Therefore, it is difficult to implement a standard treatment regimen to all elderly patients with a one-size-fits-all approach. Furthermore, it is important to evaluate the diversity of elderly patients as objectively as possible by evaluating organ functions and frailty in accordance with geriatric assessment, which helps determine the treatment plan. In addition, it is also ideal to select the treatment after considering the factors associated with tumors, such as the presence or absence of unfavorable chromosomal abnormalities.Epstein-Barr virus (EBV), the first human tumor virus, was discovered more than 55 years ago. Although EBV is carried by the majority of human population, it contributes to only a small subset of all human cancers. In individuals, this virus manifests lymphotropism, establishes latent infection, and eventually hides in resting memory B cells. However, persons who fail to maintain the virus in its latent state may develop EBV-driven lymphoproliferative disorders (LPDs) and lymphomas. B-cell LPDs and lymphomas occur predominantly in immunocompromised patients, whereas T/NK-cell LPDs and lymphomas mainly arise in immunocompetent individuals. Improved understanding of the biology of these LPDs and the role of EBV expands the potential of new therapy targeting EBV-specific molecules.Immune checkpoint blockade has been widely applied for the treatment of malignant tumors, including hematological malignancies. Nevertheless, growing evidence has indicated that there are specific situations in which somatic or germline abnormalities in gene coding for immune checkpoint-associated molecules may play a role in the development and progression of lymphoid malignancies. Somatic mutations in the PDCD1 gene and generation of the CTLA4-CD28 fusion gene have been reported in T-cell lymphomas and are considered to be involved in disease progression. By contrast, rare germline variants in CTLA4 and HAVCR2 are suggested to be associated with the predisposition to immunodeficiency-associated lymphomas and subcutaneous panniculitis-like T-cell lymphoma, respectively. Angiogenesis inhibitor Abnormalities in the associated molecules may alter the properties of lymphocytes and contribute to cellular transformation because immune checkpoints modulate the activities and functions of lymphocytes. Many new therapies targeting immune checkpoints are under development and have been applied in clinics, and notably, immune checkpoint blockade may lead to an unexpected deterioration in health or the development of new lymphoid malignancies in some specific situations.Molecular targeted therapies with small molecule inhibitors and antibodies have rapidly replaced chemoimmunotherapy, which has been the gold standard of care for patients with chronic lymphocytic leukemia (CLL). We discuss the current treatment strategies for CLL with special emphasis on genomic and molecular risk factors including IGHV unmutated status, 11q deletion, and 17p deletion. Ibrutinib and venetoclax are two molecular targeted agents currently available in Japan. They are highly effective, well tolerated, and have improved overall survival. Therefore, molecular targeted therapies are preferred to chemoimmunotherapy for most patients. Ongoing studies will clarify the optimal option between combination and sequence of treatment regimens with an appropriate timing of therapeutic intervention for longer survival. We are nearing an era of chemotherapy-free CLL management.The development of targeted therapies, such as rituximab-an anti-CD20 antibody targeting CD20, has undergone a paradigm shift from conventional chemotherapy for malignant lymphoma (ML). Although a subset of ML patients has been cured, the treatment of refractory and relapsed diseases remains challenging. Fortunately, growing insights on molecular biology for ML have led to the development of a number of innovative agents. Moreover, a plethora of targeted therapies, including novel antibodies targeting surface antigens, and small molecular inhibitors targeting oncogenic signaling pathways, tumor suppressors, and epigenetic regulation are currently under investigation for the improvement of dismal prognosis. In addition, immunotherapies, including immune checkpoint inhibitors, bispecific T-cell engager antibodies, and chimeric antigen receptor T-cells for ML have been rapidly developed to target tumor microenvironment. These promising mechanism-based targeted therapies could lead to a successful ML management.Peripheral T-cell lymphoma (PTCL) is a kind of aggressive lymphoma with a poorer prognosis than mature B-cell lymphoma. Presently, the standard of care for PTCL is considered to be the CHOP regimen, yet clinical outcomes remain insufficient. The intensification of chemotherapy and front-line high-dose chemotherapy have been examined as potential therapeutic strategies by several clinical trials. A recent double-blind phase III trial examining the effects of brentuximab vedotin (BV) when incorporated into front-line chemotherapy involved CD30-positive PTCL cases and found that a progression-free survival benefit was observed by adding BV to the therapeutic regimen, especially in the context of anaplastic large-cell lymphoma. Other molecular target agents, i.e., antibodies and small molecules, have also actively been developed. Investigators should conduct further clinical trials to establish the next standard treatment by the optimization of classic chemotherapeutic agents and molecular target agents.Follicular lymphoma (FL) is incurable with the current standard therapeutic strategy despite improvements of the natural history of FL in the last few decades. For advanced-stage patients with low-tumor burden, watchful waiting remains the standard treatment. The optimal timing of rituximab monotherapy has not been elucidated. For advanced-stage patients with high-tumor burden, anti-CD20 monoclonal antibody and chemotherapy are the standard care. A subset of FL patients who had early progression of relapse within 24 months has a significantly poor prognosis. Among the early progression of the disease group, more early progression and transformation are important factors. Recently, genomic analysis suggests that high-risk biology may depend on the type of chemotherapy. Therefore, the genomic profile could help develop appropriate treatment selection in the future. This review includes the current FL treatment strategy and prognostic factors.Interim positron emission tomography (iPET-2)-guided therapy following two cycles of ABVD chemotherapy has been developed for newly diagnosed classical Hodgkin lymphoma (cHL) patients in several prospective trials. In localized-stage cHL, radiotherapy cannot be omitted, even in iPET-negative patients after two or three cycles of ABVD, whereas two cycles of escalated BEACOPP regimens followed by involved nodular radiotherapy (30 Gy) is a useful treatment option for iPET-2 positive patients after two cycles of ABVD. In advanced-stage cHL, approximately 20% of cases were iPET-2 positive, and the switch to BEACOPP-based regimens was reported as a useful treatment option, with 3-year progression-free survival of approximately 60-65%, in iPET-2-positive patients in three clinical trials. Furthermore, the switch to AVD (omission of bleomycin after two cycles of ABVD) is a reasonable treatment option in iPET-2-negative patients, particularly those at risk for bleomycin lung toxicity in advanced-stage cHL. This review summarizes the current evidence regarding interim PET-guided therapy for newly diagnosed cHL patients.
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