Publications by authors named "Takafumi Yokota"

Inappropriate discontinuation of immunosuppressive drugs (ISD) following allogeneic hematopoietic cell transplantation (HCT) can lead to the development of chronic graft-versus-host disease (cGVHD) and necessitate the reintroduction of ISD. However, only a few studies have compared the discontinuation rates of secondary steroid for cGVHD between different stem cell sources. We retrospectively evaluated 191 patients who underwent HCT at our institution to determine the discontinuation rates of secondary steroids for cGVHD.

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Background: Infectious diseases remain a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Secondary hypogammaglobulinemia is a risk factor for infectious diseases. Total immunoglobulin G (IgG) levels and the history of infectious diseases are an integral part of determining the indication for immunoglobulin replacement therapy.

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Mitochondria transfer is a recently described phenomenon in which donor cells deliver mitochondria to acceptor cells. One possible consequence of mitochondria transfer is energetic support of neighbouring cells; for example, exogenous healthy mitochondria can rescue cell-intrinsic defects in mitochondrial metabolism in cultured ρ cells or Ndufs4 peritoneal macrophages. Exposing haematopoietic stem cells to purified mitochondria before autologous haematopoietic stem cell transplantation allowed for treatment of anaemia in patients with large-scale mitochondrial DNA mutations, and mitochondria transplantation was shown to minimize ischaemic damage to the heart, brain and limbs.

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  • Ahed is a newly identified gene in haematopoiesis that plays a crucial role in blood cell development, discovered through screening mutant embryonic stem cells.
  • Conditional knockout of Ahed leads to severe anemia and prenatal death, as its absence hampers the ability of haematopoietic cells to regenerate in living organisms.
  • Deletion of Ahed disrupts multiple biological pathways in adult mice and is linked to mutations found in cancer patients, highlighting its importance in both normal blood development and potential involvement in cancers.
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  • Asciminib is a groundbreaking medication for chronic myeloid leukemia (CML) that targets a specific pocket in the ABL1 protein and is approved for patients resistant or intolerant to prior treatments.
  • In the Phase 3 ASCEMBL study, Japanese patients showed a 46.2% major molecular response (MMR) at 96 weeks while on asciminib, with high retention rates compared to those on bosutinib, who all discontinued treatment by Week 96.
  • The safety profile for asciminib remained strong over time, with similar effectiveness and tolerability in the Japanese subgroup compared to the broader global study population, indicating it is a suitable treatment option for these patients.
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  • Accurate differentiation between donor-derived post-transplant lymphoproliferative disorder (PTLD) and relapsed recipient-derived lymphoproliferative disorder (LPD) is essential for effective treatment post-hematopoietic stem cell transplantation (HSCT).
  • Traditional diagnostic methods often fall short, especially in cases involving Epstein-Barr virus (EBV)-positive LPDs with low tumor cell counts.
  • The newly developed method utilizes sex chromosome fluorescence in situ hybridization and other techniques on a single tissue section, successfully enabling accurate diagnosis of difficult cases and preserving histological structure.
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Patients with relapsed or refractory acute myeloid leukemia (RR-AML) with mutations of FMS-like tyrosine kinase 3 (FLT3) have a poor prognosis even after allogeneic hematopoietic cell transplantation (allo-HCT). Multiple FLT3 inhibitors, including gilteritinib, have been developed and serve as treatment options for RR-AML. Here, we describe three cases of FLT3 mutated RR-AML that were successfully treated with gilteritinib administration before and after allo-HCT.

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Immunoglobulin replacement therapy (IgRT) reduces the risk of infection in hypogammaglobulinaemia secondary to chronic lymphocytic leukaemia and multiple myeloma. However, the benefit of IgRT, especially subcutaneous IgRT (ScIgRT), has not been assessed in hypogammaglobulinaemia after allogeneic haematopoietic cell transplantation (allo-HCT). We performed a pre-post comparison of the clinical impact of ScIgRT after allo-HCT in a retrospective analysis of 209 patients who underwent allogeneic HCT at our institution from 2011 to 2019.

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Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for hematological malignancies. Several complications following allo-HSCT, such as graft-versus-host disease, infection, and malnutrition, often cause physical dysfunction, and the assessment of physical function and evaluation of muscle mass are incompletely performed. Use of ultrasound (US) allows muscle mass measurement in patients with poor general conditions.

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Patients who have undergone hematopoietic cell transplantation (HCT) are at a higher risk of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection than the general population. Therefore, early vaccination is recommended for post-transplant patients. Although exacerbation of chronic graft-versus-host disease (cGVHD) after the initial vaccination has been reported, it is unknown whether severe cGVHD occurs when different RNA vaccines are combined.

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A 48-year-old male patient developed acute myeloid leukemia (AML) with t(3;3)(q21.3;q26.2) chromosomal mutation 8 months after orthotopic heart transplantation from a human leukocyte antigen-unmatched brain-dead donor for cardiac sarcoidosis.

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Article Synopsis
  • * An 86-year-old woman experienced bleeding symptoms (purpura) after receiving the BNT162b2 mRNA COVID-19 vaccine, which worsened after her second dose, leading to her hospital referral.
  • * Diagnosed with AHA, the woman was treated with prednisolone, resulting in complete remission, highlighting the importance of monitoring for bleeding symptoms post-vaccination.
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Dysbiosis of the gut microbiota has been reported to increase early complications after allogeneic haematopoietic stem cell transplantation (allo-HSCT). However, it remains unclear whether gut microbial alterations persist during late complications, such as chronic graft-versus-host disease (cGVHD) or secondary cancers. Here, we analysed the gut microbiota of 59 patients who survived for 1-21.

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Asciminib, a first-in-class, allosteric inhibitor of BCR-ABL1 that acts by STAMP (Specifically Targeting the ABL Myristoyl Pocket), is a novel therapeutic option for patients with chronic myeloid leukemia (CML). In the global, phase 3, open-label ASCEMBL study in patients with CML in chronic phase (CML-CP) pretreated with ≥2 tyrosine kinase inhibitors (TKIs) (NCT03106779), asciminib (40 mg twice-daily) demonstrated significant superiority over the ATP-competitive TKI bosutinib (500 mg once daily) for the primary endpoint of major molecular response (MMR; BCR::ABL1 transcript levels on the international scale [BCR::ABL1 ] ≤0.1%) at week 24.

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  • Hematopoietic stem cells (HSCs) are crucial for producing blood and immune cells, but the precise methods of their differentiation and how aging affects this process are still not fully understood.
  • Researchers identified two important molecules, ESAM and SATB1, which play key roles in marking HSCs and guiding their differentiation towards lymphoid cells.
  • Findings show that while the expression of SATB1 decreases with age, boosting its levels in older HSCs can restore their ability to produce lymphoid cells, highlighting the potential for rejuvenating aged HSCs.
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Epigenetic mechanisms underpin the elaborate activities of essential transcription factors in lymphocyte development. Special AT-rich sequence-binding protein 1 (SATB1) is a chromatin remodeler that orchestrates the spatial and temporal actions of transcription factors. Previous studies have revealed the significance of SATB1 in T cell lineage.

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Anamorsin (AM) is an anti-apoptotic molecule cloned by us as a molecule that confers resistance against apoptosis induced by growth factor deprivation. AM-deficient mice are embryonic lethal, which impedes detailed analyses of the roles of AM in various types of adult cells. To overcome the embryonic lethality, we generated AM conditional knockout (AM) mice and cell type-specific genetic modification became possible using the Cre-loxP system.

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  • * Two heavily treated elderly patients responded well to this sequential therapy, achieving complete molecular remission without severe side effects typically associated with other treatments.
  • * The therapy shows potential as a bridging regimen before allogeneic stem cell transplantation, although further preventative measures for central nervous system issues are recommended.
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  • * A 56-year-old man with advanced melanoma developed swelling in his lymph nodes and anemia after receiving nivolumab treatment, but tests showed no signs of cancer.
  • * The patient was diagnosed with reactive lymphadenopathy caused by nivolumab, and he was treated with corticosteroids, which successfully resolved the symptoms.
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FMS-like tyrosine kinase 3-internal tandem duplication (-ITD) mutation-positive acute myeloid leukemia (AML) has a poor prognosis. We report the first case of successful bridge therapy of novel FLT3 inhibitor, quizartinib, to umbilical cord blood stem cell transplantation for -ITD-positive AML-primary induction failure patients with central nervous system involvement.

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Autoimmune hematological disorders are rare complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis of immune thrombocytopenia (ITP) is challenging, especially after allo-HSCT, because various complications such as graft-versus-host disease, disease relapse, viral infection, thrombotic microangiopathy, and drug side effects can also cause thrombocytopenia. Assessment of reticulated platelets (RP) and plasma thrombopoietin (TPO) levels may be useful to distinguish between ITP and hypoplastic thrombocytopenia.

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Poor graft function (PGF) is a fatal complication following hematopoietic stem cell transplantation and is influenced by multiple factors, such as donor-specific anti-HLA antibodies, a poor infused CD34 cell count, and the donor source. Alloantibodies against human platelet antigen 15 (HPA-15) recognize platelet membrane glycoprotein CD109, which is expressed not only on platelets, but also on megakaryocytes and specific hematopoietic stem cells. HPA-15 antibodies are known to induce platelet transfusion refractoriness and neonatal alloimmune thrombocytopenia, but their effects on graft function following hematopoietic stem cell transplantation remain unknown.

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