Publications by authors named "Takaori-Kondo A"

Craniocervical edema appears soon after chimeric antigen receptor T-cell (CAR-T) therapy in some cases. This phenomenon is often observed right after systemic cytokine release syndrome (CRS), and it is called local CRS (L-CRS). In severe cases, L-CRS causes airway obstruction and asphyxia, but it is not yet well known among hematologists.

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Graft-versus-host disease (GVHD) is less common in autologous stem cell transplantation (ASCT) recipients than in allogeneic SCT recipients. However, some cases of severe GVHD, especially involving the gastrointestinal (GI) tract, have been documented. We present a patient with primary central nervous system lymphoma (PCNSL) exhibiting severe GI-GVHD after ASCT with busulfan/thiotepa conditioning.

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The maintenance of cellular redox balance is crucial for cell survival and homeostasis and is disrupted with aging. Selenoproteins, comprising essential antioxidant enzymes, raise intriguing questions about their involvement in hematopoietic aging and potential reversibility. Motivated by our observation of mRNA downregulation of key antioxidant selenoproteins in aged human hematopoietic stem cells (HSCs) and previous findings of increased lipid peroxidation in aged hematopoiesis, we employed tRNASec gene (Trsp) knockout (KO) mouse model to simulate disrupted selenoprotein synthesis.

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Introduction: Patients undergoing chimeric antigen receptor (CAR) T-cell therapy face prolonged treatment timelines and are prone to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) after infusion. Disabilities in physical function and the importance of rehabilitation during CAR-T-cell therapy to maintain physical function have been poorly documented.

Method: We performed a retrospective cohort study to assess changes in exercise tolerance via differences in a 6-min-walking distance (Δ6MWD) and factors influencing it.

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Background Aims: Methotrexate (MTX) is used as standard graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation. However, the optimal dosing regimen among the various MTX regimens available remains unclear.

Methods: We used the registration data of Kyoto Stem Cell Transplantation Group to compare six MTX dosing protocols in a multicenter retrospective analysis of 816 cases of unrelated bone marrow or peripheral blood stem cell transplantation.

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The linear ubiquitin chain assembly complex (LUBAC) plays crucial roles in NF-κB signaling and protection against cell death by generating linear ubiquitin chains. Its accessory subunits, HOIL-1L and SHARPIN, regulate LUBAC function by binding to ubiquitin chains via their Npl4 zinc finger (NZF) domains. However, the synergistic effects of the two NZF domains on LUBAC function remain unclear.

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Article Synopsis
  • * Despite hematological remission, the patient’s vision did not recover after treatment with intrathecal cytotoxic drugs, and her overall condition deteriorated due to progressive disease.
  • * Investigations showed low levels of gilteritinib in the cerebrospinal fluid and the emergence of a mutation associated with resistance to the drug, highlighting the challenges of treating CNS involvement in leukemia.
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Structural variations involving enhancer hijacking induce aberrant oncogene expression and cause tumorigenesis. A rare translocation, t(3;8)(q26.2;q24), is associated with MECOM and MYC rearrangement, causing myeloid neoplasms with a dismal prognosis.

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The prognosis for multiple myeloma (MM) patients has improved with the advent of new drugs, but the prognosis with renal impairment (RI) is poor. The choice of treatment in such cases is critical, but there are no set criteria. We examined the impact of RI on initial therapy in transplant-ineligible MM patients.

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Article Synopsis
  • Researchers used a 5' single-cell RNA sequencing method to identify where enhancer RNAs and other RNA types start in human CD4 T cells, uncovering variations in cell types and their development.
  • By combining these RNA datasets with single-cell chromatin profiles, they found that unique active enhancers and their RNA production are specific to certain cell types and are linked to disease risk.
  • The study created a detailed atlas of these enhancers that helps to understand how genetic variations are related to various immune-mediated diseases.
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Familial hemophagocytic lymphohistiocytosis (FHL) is a rare inherited autosomal recessive immune deficiency that usually manifests during infancy or early childhood, rarely occurring in adults. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for FHL. However, optimal conditioning regimens for adult-onset FHL have not yet been established.

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Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for B cell malignancies. A certain fraction of patients, however, experience post-CAR-T relapse, and due to the difficulty of precise relapse prediction, biomarkers that can predict the strength and duration of CAR-T efficacy are needed before CAR-T infusion. Therefore, we performed a single-center cohort study including 91 diffuse large B cell lymphoma (DLBCL) patients treated with CAR-T in order to identify such a new prognostic biomarker.

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Background: Isatuximab, an anti-CD38 antibody, has been widely used in treatments for patients with relapsed/refractory multiple myeloma (MM). Despite its high efficacy, not all patients achieve a lasting therapeutic response with isatuximab.

Objective: We tried to identify biomarkers to predict the effectiveness of isatuximab by focusing on the host's immune status before treatment.

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The viral infectivity factor (Vif) of human immunodeficiency virus 1 forms a complex with host proteins, designated as Vif-CBFβ-ELOB-ELOC-CUL5 (VβBCC), initiating the ubiquitination and subsequent proteasomal degradation of the human antiviral protein APOBEC3G (A3G), thereby negating its antiviral function. Whilst recent cryo-electron microscopy (cryo-EM) studies have implicated RNA molecules in the Vif-A3G interaction that leads to A3G ubiquitination, our findings indicated that the VβBCC complex can also directly impede A3G-mediated DNA deamination, bypassing the proteasomal degradation pathway. Employing the Systematic Evolution of Ligands by EXponential enrichment (SELEX) method, we have identified RNA aptamers with high affinity for the VβBCC complex.

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Article Synopsis
  • Posaconazole is important for treating fungal infections, but its pharmacokinetics (how the drug is processed in the body) can be influenced by factors such as HSCT, body weight, and diet.
  • A study examined the factors affecting posaconazole levels in Japanese patients, finding that almost 30% had low drug levels below the effective range, especially in those who had undergone HSCT or experienced frequent diarrhea.
  • The results suggest that monitoring posaconazole levels is crucial for patients, particularly after HSCT or during digestive issues, to prevent inadequate treatment of serious fungal infections.
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A primary reason for the ongoing spread of coronavirus disease 2019 (COVID-19) is the continuous acquisition of mutations by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanism of acquiring mutations is not fully understood. In this study, we isolated SARS-CoV-2 from an immunocompromized patient persistently infected with Omicron strain BF.

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Allogenic hematopoietic stem cell transplantation (allo-HSCT) is not a standard therapy for solid cancer because of its high toxicity and insufficient evidence levels. However, the potential graft-versus-solid-tumor (GVT) effect of this therapy has been discussed. Many case reports have also described treatment effects of allo-HSCT in patients with hematologic malignancies and active solid tumors.

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  • Elotuzumab is sometimes used for multiple myeloma treatment after daratumumab, but its effectiveness in this sequence is under-researched.
  • A study found that patients receiving elotuzumab after daratumumab had significantly worse overall survival and time to next treatment compared to those who hadn’t previously used daratumumab.
  • Results indicated that elotuzumab should ideally be administered at least 180 days after daratumumab to improve patient outcomes, suggesting that treatments without monoclonal antibodies might be a better option following daratumumab regimens.
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T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has a poor prognosis. Nelarabine has recently shown relatively good results in patients with relapsed or refractory T-ALL/LBL, but requires careful monitoring for neurological complications. A 50-year-old man with early recurrence of T-LBL after allogenic peripheral blood stem cell transplantation received nelarabine monotherapy and achieved complete remission after 1 cycle.

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Morphological dysplasia in haematopoietic cells, defined by a 10% threshold in each lineage, is one of the diagnostic criteria for myelodysplastic neoplasms. Dysplasia limited to the erythroid lineage has also been reported in some cases of aplastic anaemia (AA); however, its significance remains unclear. We herein examined the impact of erythroid dysplasia on immunosuppressive therapy responses and survival in AA patients.

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Prolonged hematotoxicity is the most common long-term adverse event in chimeric antigen receptor T cell therapy (CAR-T). To evaluate the impact on prolonged cytopenia of inflammatory status after CAR T infusion, we performed a single-center retrospective study and analyzed patients with B cell lymphomas after CAR-T. Among 90 patients analyzed at 90 days after infusion, the cumulative incidence was 57.

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  • Subacute myelopathy is a rare but severe side effect of methotrexate (MTX) that can lead to paraplegia, with homocysteine potentially playing a role in its development.
  • A case study involves a 34-year-old woman with diffuse large B-cell lymphoma who experienced progressive paraplegia and bladder/bowel dysfunction after receiving a chemotherapy regimen that included high-dose MTX.
  • Symptoms improved significantly within 4.5 months after receiving a treatment combination of S-adenosylmethionine, methionine, cyanocobalamin, and folate, highlighting the need for careful monitoring and early intervention during high-dose MTX treatment.
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