Publications by authors named "Takahiro Kumode"

Background: In a global phase I/II study (GO29781; NCT02500407), single-agent mosunetuzumab had a manageable safety profile and induced durable complete responses in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma, including in patients with R/R follicular lymphoma (FL). In this analysis, the efficacy and safety of mosunetuzumab monotherapy were evaluated in an expansion cohort, FLMOON-1, in Japanese patients with R/R FL who had received  ≥ 2 prior lines of therapy in a phase I study (JO40295, jRCT2080223801).

Methods: Mosunetuzumab was administered intravenously at the recommended phase II dose (with cycle 1 step-up dosing) for eight cycles or up to 17 cycles, or until disease progression or unacceptable toxicity.

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  • * The Orbit study aimed to evaluate real-world outcomes for adults with CLL/SLL in Japan treated with ibrutinib between July 2018 and December 2020, including 246 patients in total.
  • * After 36 months, the study showed an 80.9% progression-free survival rate for first-line treatment and 67.2% for relapsed cases, with common significant side effects including bleeding and infections, underscoring ibr
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Despite the introduction of new drugs, multiple myeloma (MM) still remains incurable. We previously reported that CD34 MM cells, which are clonogenic and self-renewing, are therapy-resistant and persist as a major component of minimal residual disease, expanding during relapse. To investigate the effects of immunotherapies such as immune-checkpoint inhibitors, CAR-T therapy, and bispecific antibodies on CD34 MM cells, we analyzed immune profiles of both MM cells and T cells from MM patients using microarrays and flow cytometry.

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  • - Epcoritamab, a bispecific antibody targeting CD3 and CD20, showed promising results in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in a global phase II trial (EPCORE NHL-1), demonstrating deep and lasting responses with manageable side effects.
  • - The phase I/II trial (EPCORE NHL-3) focused on Japanese patients with R/R CD20 B-cell non-Hodgkin's lymphoma who had received two or more prior treatments, revealing an overall response rate of 55.6% and a complete response rate of 44.4% at a median follow-up of 8.4 months after receiving subcutaneous epcoritamab.
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We retrospectively evaluated long-term outcomes of high dose chemotherapy followed by autologous stem cell transplant (HDC/ASCT) in patients with diffuse large B-cell lymphoma (DLBCL). Between 2004 and 2020, 46 DLBCL patients received HDC/ASCT in our institution, including 12 patients (26.1%), who received as an upfront setting (UFS).

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  • The antipsychotic drug chlorpromazine (CPZ) inhibits the growth of non-small cell lung cancer cells with mutated epidermal growth factor receptor (EGFR) by disrupting cellular transport and localization of EGFR.
  • CPZ not only reduced the survival of gefitinib-resistant lung cancer cells but also restored their sensitivity to the drug, indicating a potential for overcoming drug resistance.
  • The study found that while CPZ does not affect EGFR phosphorylation, it significantly lowers the phosphorylation of related pathways (ERK and AKT) and alters the distribution of EGFR within cells, suggesting a unique mechanism for its therapeutic effects on lung cancer.
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Side population (SP) is known to include therapy-resistant cells in various cancers. Here, we analyzed SP using multiple myeloma (MM) samples. The SP accounted for 2.

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C-type lectin-like receptor 2 (CLEC-2) expressed on megakaryocytes plays important roles in megakaryopoiesis. We found that CLEC-2 was expressed in about 20% of phenotypical long-term hematopoietic stem cells (LT-HSCs), which expressed lower levels of HSC-specific genes and produced larger amounts of megakaryocyte-related molecules than CLEC-2 LT-HSCs. Although CLEC-2 LT-HSCs had immature clonogenic activity, cultured CLEC-2 LT-HSCs preferentially differentiated into megakaryocytes.

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Acute myeloid leukemia (AML) is a heterogeneous disease often associated with poor prognosis. We previously showed that the localization of KIT-D816V at endolysosomes is critical to activate aberrant Akt signaling and Chlorpromazine (CPZ) perturbs the intracellular localization, leading to cell death in AML cells with . We report that daily administration of CPZ, prescribed for controlling anxiety disorder in patient with AML harboring , led to a dramatic reduction in AML cells.

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  • The trial aimed to assess the effectiveness of rituximab-bendamustine (R-B) in patients with untreated advanced follicular lymphoma (FL) who showed a non-optimal response (nOR) to initial treatment with R-CHOP.
  • Out of 56 patients receiving R-CHOP, 43 were categorized as having nOR and transitioned to 6 cycles of R-B, resulting in a 3-year progression-free survival rate of 69.0% and an overall survival rate of 92.7% at a median follow-up of 50.6 months.
  • The study identified low absolute lymphocyte count as a significant poor prognostic factor for both progression-free and overall survival, with similar
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We report a case with extramedullary tumors affecting the supraclavicular region that presented as a relapse of acute myeloid leukemia (AML) with FLT3-ITD mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Treatment with gilteritinib resulted in remarkable response with disappearance of both the medullary and extramedullary tumors. Subsequently, a 2nd allo-HSCT was performed in an attempt to cure his AML and complete molecular response has been sustained with gilteritinib resumption without worsening GVHD.

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  • * The protein CALM is important for transporting RTKs in cells, and its knockdown significantly hinders growth of cells with MT-RTKs compared to those with wild-type RTKs.
  • * The antipsychotic drug chlorpromazine (CPZ) is shown to inhibit the growth of AML cells with MT-RTKs by lowering CALM levels and disrupting MT-RTK signaling, suggesting a new treatment approach for AML.
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Despite duodenal-type follicular lymphoma (DTFL) being morphologically, immunophenotypically and genetically indistinguishable from nodal FL (nFL), this entity typically shows a significantly better prognosis. Here, we analysed the tumour immune microenvironments of diagnostic specimens from patients with DTFL (n = 30), limited-stage FL (LSFL; n = 19) and advanced-stage FL (ASFL; n = 31). The mean number of CD8 tumour-infiltrating lymphocytes (TILs) in the neoplastic follicles was higher in DTFL (1,827/mm ) than in LSFL (1,150/mm ) and ASFL (1,188/mm ) (P = 0·002, P = 0·002, respectively).

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  • * A case is reported of a 30-year-old woman who developed post-transplant lymphoproliferative disorder (PTLD) linked to Epstein-Barr virus (EBV) reactivation after undergoing stem cell transplantation for severe aplastic anemia.
  • * The PTLD was localized in the brain, leading to symptoms of increased intracranial pressure; however, after treatment with high dose methotrexate and rituximab, the patient fully recovered, with normalized blood counts
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An 80-year-old woman experienced dyspnea. Cardiac enlargement was detected by chest radiography at a local hospital. She was admitted to our hospital, and echocardiography and CT revealed pericardial effusion and multiple tumor lesions in right atrium.

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  • - A 62-year-old man with chronic lymphocytic leukemia (CLL) experienced a partial response to treatment for nine years, but later developed rapidly growing lymphadenopathy diagnosed as de novo lymphocyte-rich classic Hodgkin lymphoproliferative diseases (LPDs) alongside small lymphocytic lymphoma (SLL).
  • - Biopsy results showed Hodgkin/Reed-Sternberg (HRS) cells that were genetically unrelated to his preexisting CLL, indicating a new and distinct condition.
  • - The patient was successfully treated with Bendamustine and Rituximab (BR), resulting in complete remission for over a year, suggesting BR as an effective option for both Hodgkin LPDs and SLL
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Myeloproliferative neoplasms (MPNs), including polycythemia vera and essential thrombocythemia, are frequently associated with thrombotic complications. Prevention of thrombotic events is thus a primary aim of the current treatment for these disorders. Although it is known that microparticles (MPs), which are small vesicles released from cell membranes and circulate in the blood, directly contribute to thrombosis via their procoagulant activity, potential associations between plasma levels of MPs and the risk of thrombotic events in MPNs have not been reported.

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  • Hemophagocytic lymphohistiocytosis (HLH) is commonly linked with autoimmune diseases like systemic juvenile idiopathic arthritis and lupus, but this case is notable as it involves HLH with dermatomyositis and a rare complication of leukoencephalopathy.
  • A 17-year-old male with dermatomyositis and HLH experienced severe symptoms, leading to the discovery of brain lesions diagnosed as leukoencephalopathy, which were unresponsive to initial steroid treatments.
  • Treatment with a modified HLH-2004 protocol including etoposide successfully resolved the brain lesions, indicating that aggressive treatment may be crucial for HLH patients with central nervous system involvement, potentially considering bone marrow transplantation.
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Elderly patients with secondary acute myeloid leukemia (AML) following myelodysplastic syndrome (MDS) are often medically unfit for or resistant to chemotherapy, and their prognosis is dismal. In the present paper, we reported a case of secondary leukemia following MDS in an 80-year-old male patient who was deemed unfit for chemotherapy owing to his old age and poor physical condition. Despite a high tumor burden, treatment with AZA exerted a remarkable response, leading to an immediate cytoreduction in our case.

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Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma that usually develops in immunosuppressed patients infected with human herpes virus-8 (HHV-8) in conjunction with human immunodeficiency virus (HIV) infection. However, there are several reports of HHV-8-related HIV-negative cases and HHV-8-unrelated HIV-negative cases, mainly in immunodeficient and elderly patients. Here, we report one case of HHV-8-related HIV-negative PEL with gastric cancer (case 1) and one case of HHV-8-unrelated HIV-negative effusion-based lymphoma (case 2), both in elderly men.

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