Publications by authors named "Atsushi Kikuta"

T cell-replete haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) is a potentially curative therapy for pediatric intractable hematological malignancies due to its graft-versus-leukemia efficacy. This single-center cohort study examined the effects of graft composition (T cell type and dose) on pediatric TCR-haplo-HSCT outcomes in 32 children with relapsed/intractable hematological malignancies. Graft T cell composition was classified using flow cytometry.

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Article Synopsis
  • The ALL-R08 study in Japan focuses on children with first-relapsed acute lymphoblastic leukemia (ALL) to evaluate the effectiveness of the BFM-S classification and measurable residual disease (MRD) as prognostic tools for patient survival.
  • The study consists of two parts: an observational study (ALL-R08-I) and a clinical trial (ALL-R08-II) that differentiates treatment based on MRD levels after induction therapy.
  • Results showed varying 3-year event-free survival rates across different BFM-S groups, indicating that children treated with either Japanese or BFM-type protocols have similar outcomes for managing first-relapsed ALL.
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Purpose: High-dose methotrexate therapy (HD-MTX) is a standard treatment for various malignant tumors, but approximately 1-10% of patients experience delayed MTX elimination (DME) that can induce organ damage. Glucarpidase can hydrolyze MTX and thereby lower the level of active MTX in the blood. A multicenter, open-label, phase II investigator-initiated trial (CPG2-PII study) was conducted to evaluate glucarpidase rescue therapy in Japanese patients who showed DME after HD-MTX treatment.

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Background: In children with intermediate-risk relapsed acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) has markedly improved the outcome of patients with an unsatisfactory minimal residual disease (MRD) response. Total body irradiation (TBI), etoposide (ETP), and cyclophosphamide (CY) have been shown to be equivalent to or better than TBI + ETP for conditioning, so we hypothesized that even greater survival could be achieved due to recent advances in HSCT and supportive care.

Procedure: We prospectively analyzed the efficacy and safety of allo-HSCT with a unified conditioning regimen of TBI + ETP + CY in children with intermediate-risk relapsed ALL, based on MRD in the bone marrow after induction, from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) ALL-R08-II nationwide cohort (UMIN000002025).

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Treatment outcomes for children with relapsed and refractory acute lymphoblastic leukemia (R/R-ALL) remain poor, and the optimal induction therapy has not been determined. Bortezomib is a proteasome inhibitor that acts synergistically and additively with standard chemotherapy for ALL. We evaluated the efficacy and safety of combination chemotherapy with bortezomib in children with R/R-ALL.

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Introduction: Glucarpidase (CPG2) reduces the lethal toxicity of methotrexate (MTX) by rapid degradation.

Methods: In this study, a CPG2 population pharmacokinetics (popPK) analysis in healthy volunteers (phase 1 study) and a popPK-pharmacodynamics (popPK-PD) analysis in patients (phase 2 study, = 15) who received 50 U/kg of CPG2 rescue for delayed MTX excretion were conducted. In the phase 2 study, the first CPG2 treatment at a dose of 50 U/kg was intravenously administered for 5 min within 12 h after the first confirmation of delayed MTX excretion.

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Chimerism analysis is a surrogate indicator of graft rejection or relapse after allogeneic hematopoietic stem cell transplantation (HSCT). Although short tandem repeat PCR (STR-PCR) is the usual method, limited sensitivity and technical variability are matters of concern. Quantitative PCR-based methods to detect single nucleotide polymorphisms (SNP-qPCR) are more sensitive, but their informativity and quantitative accuracy are highly variable.

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TCF3-HLF-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has an extremely poor prognosis. A 2-year-old boy with TCF3-HLF-positive BCP-ALL had an isolated extramedullary relapse in multiple bones after allogeneic hematopoietic stem cells transplantation (HSCT) from a human leukocyte antigen-matched unrelated donor. In this study, he received a T-cell-replete haploidentical HSCT (TCR-haplo-HSCT) from his father when in nonremission state, which resulted in a sustained complete remission for over 3 years.

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the preferred treatment for children with high-risk hematologic malignancies, but post-allo-HSCT relapse has a poor prognosis and limited treatment options. We evaluated the feasibility, outcome, and risk factors influencing survival after T-cell-replete haploidentical HSCT with low-dose anti-thymocyte globulin (ATG) in 30 patients with post-allo-HSCT relapse of acute lymphoblastic leukemia and acute myeloid leukemia. Overall, 50% of the patients had complete remission (CR) before the second transplant and the overall survival (OS) rate was 52%.

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The prognosis of refractory/relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains dismal owing to acquired resistance to chemotherapeutic agents. This study aimed to evaluate the efficacy of T-cell replete HLA haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) for pediatric refractory/relapsed BCP-ALL (RR-BCP-ALL). Nineteen pediatric patients with RR-BCP-ALL underwent TCR-haplo-HSCT between 2010 and 2019 at the Fukushima Medical University Hospital.

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Article Synopsis
  • - The study focuses on developing a cancer vaccine that activates the body's immune response to fight pre-established tumors using a new type of immune cell called alloantigen-activated CD4 (AAA-CD4) T cells, derived from donor mice.
  • - Researchers injected AAA-CD4 T cells into mice with existing melanoma, leading to a significant immune response characterized by the expansion of various immune cells and high production of immune signaling molecules.
  • - The treatment not only destroyed the primary tumors but also provided lasting immunity, successfully eliminating tumors at distant sites and offering protection for over six months.
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Sinusoidal obstruction syndrome (SOS), also called veno-occlusive disease (VOD) of the liver, is one of the most relevant complications of hepatic sinusoidal endothelial origin that appears early after hematopoietic cell transplantation (HCT). Despite its relatively low incidence and the spontaneous resolution of most SOS/VOD cases, severe SOS/VOD evolved to multi-organ failure with an >80% mortality rate and represents one of the major clinical problems after HCT. The sinusoidal endothelial cells and hepatocytes are damaged by toxic metabolites generated by the conditioning regimen in these patients.

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Although approximately 70% of pediatric hematological malignancies are curable, approximately 30% remain fatal. No standard treatment is available in patients showing relapse and those with refractory disease. Although different methods are adopted in different hospitals, its efficacy is extremely limited.

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Background: Despite intensive multimodal therapies, the prognosis of relapsed/ refractory Ewing sarcoma family tumors (RR-ESFTs) is dismal. Some case reports using allogeneic stem cell transplantation (allo SCT) for RR-ESFTs have been reported, however, the efficacy of allo SCT is yet to be established.

Aim: The purpose of this study was to evaluate the response and toxicity of T-cell replete haploidentical SCT (TCR-haplo-SCT) in RR-ESFTs.

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Chronic myeloid leukemia (CML) is an uncommon entity in pediatric patients. CML in chronic phase (CML-CP) has a relatively favorable outcome. Leukostasis occurs in 9.

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In high-risk neuroblastoma, the presence of an MYCN gain/amplification (MYCN-GA) is not always a risk factor of cancer-specific death. We herein examined the effect modification of high-dose chemotherapy with autologous hematopoietic stem cell rescue (HDC-autoSCR) in terms of the interaction between MYCN status and remission status (complete remission or very good partial remission [CR/VGPR] vs. partial remission or less [≤PR]).

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Background: Haploidentical hematopoietic stem cell transplantation (HSCT) is a useful therapy for relapsed/refractory acute leukemia or lymphoma because of the strong graft-vs-leukemia (GVL) effect. However, it is often accompanied by severe acute graft-versus-host disease (aGVHD), which is the most serious complication after haploidentical HSCT. Thus, it is important to control the severity of aGVHD while maintaining the GVL effect.

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Background: The appropriateness of allogeneic hematopoietic stem cell transplantation (HSCT) in children and adolescents with leukemia in whom complete remission is not possible remains unclear. This retrospective analysis aimed to investigate the outcomes associated with HSCT, and the risks of HSCT in children and adolescents with nonremission acute lymphoblastic leukemia (ALL).

Procedure: Data from the Japan Society for Hematopoietic Cell Transplantation registry on 325 patients with nonremission ALL (aged <21 years, with blasts in the peripheral blood and/or bone marrow) who had undergone HSCT between January 2001 and December 2015 were evaluated.

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Induction deaths (ID) remain a critical issue in the treatment of pediatric patients with acute lymphoblastic leukemia (ALL). The reported rate of ID in this population is 1% or higher. We speculate that this proportion might be lower in Japan because of mandatory hospitalization during induction therapy to manage complications.

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Background: Few clinical trials have been reported for patients with intermediate-risk neuroblastoma because of the scarcity of the disease and the variety of clinical and biological characteristics. A multidisciplinary treatment that consists of multidrug chemotherapy and surgery is expected to lead to a good prognosis with few complications. Therefore, a clinical trial for patients with intermediate-risk tumors was designed to establish a standard treatment that reduces complications and achieves good outcomes.

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Background: Almost all pediatric patients with renal tumors are diagnosed with nephroblastoma (Wilms tumor), clear cell sarcoma, or malignant rhabdoid tumor. The choice of treatment is important for relapsed and refractory patients with nephroblastoma. Furthermore, clear cell sarcoma of the kidney (CCSK) and malignant rhabdoid tumor of the kidney (MRTK) have a poor prognosis compared with nephroblastoma.

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Article Synopsis
  • The study investigates the likelihood of patients developing secondary brain tumors after undergoing cranial radiotherapy, highlighting the importance of monitoring these individuals.
  • An analysis of data over 30 years revealed that 21% of patients developed secondary tumors, with cavernomas and meningiomas being the most common types.
  • The findings suggest that ongoing annual MRI scans for survivors of cranial irradiation can facilitate early detection and management of these potential complications.
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Predictors of peripheral blood stem cell (PBSC) yield can potentially improve the comfort, safety, and efficacy of CD34+ cell collection from donors treated with recombinant human granulocyte colony-stimulating factor (G-CSF). We investigated 181 apheresis procedures on 109 healthy allogeneic donors to identify factors correlating with efficient PBSC collection. Apheresis started on Day 4 or 5 and continued up to Day 6 of G-CSF administration.

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Background: Approximately 80% to 90% of patients with low-risk rhabdomyosarcoma can be cured. However, cured patients often face long-term complications associated with the treatment. An important factor in the treatment plan is the dose of cyclophosphamide administered because the dose can have both acute and long-term side effects.

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Background: Ploidy is a highly significant prognostic factor for pediatric acute lymphoblastic leukemia (ALL). Children with hypodiploid ALL have poor outcomes despite current intensive chemotherapy. Little has been investigated with regard to hypodiploid ALL in Japanese children.

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