Publications by authors named "Yoshihiro Gocho"
Background: Hematopoietic cell transplantation (HCT) is the only curative treatment for chronic active Epstein-Barr virus infection (CAEBV). While HCT is needed at the appropriate time, there are sometimes difficulties in securing an appropriate donor, making HLA haploidentical donor an alternative option. Recently, post-transplant cyclophosphamide (PTCy) has rapidly gained popularity as a safe graft-versus-host disease (GVHD) prevention strategy for HCT from HLA haploidentical donors; however, there are only a few reports of its use for CAEBV.
View Article and Find Full Text PDFBackground: X-linked chronic granulomatous disease (X-CGD) may be associated with McLeod syndrome (MLS) as a contiguous gene deletion syndrome. MLS is characterized by the loss of XK protein along with Kx antigen on red blood cell (RBC) surfaces and late-onset neurocognitive symptoms. RBCs in healthy donors express XK protein and related Kx antigen on the surface; therefore, transfusion from random donors to patients with MLS poses a risk of Kx sensitization, leading to severe hemolysis.
View Article and Find Full Text PDFBackground: Chimeric antigen receptor T-cell (CAR-T) therapy for hematological malignancies causes a neurological complication known as immune effector cell-associated neurotoxicity syndrome (ICANS). The precise neurocognitive pathology underlying ICANS remains incompletely described. The aim of this study is to elucidate that persistent cognitive dysfunction as potential neurotoxicity of CAR-T therapy.
View Article and Find Full Text PDFETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL) associated with favorable prognosis, but the optimal therapy for this subtype remains unclear. Profiling the genomic and pharmacological landscape of 194 pediatric ETV6::RUNX1 ALL cases, we uncover two transcriptomic clusters, C1 (61%) and C2 (39%). Compared to C1, the C2 subtype features higher white blood cell counts and younger age at diagnosis, as well as better early treatment responses.
View Article and Find Full Text PDFIn 2022-23, several European countries reported paediatric acute liver failure (ALF) with enterovirus infection. In August-November 2024, three neonatal cases of ALF with echovirus 11 (E11) were reported in Tokyo, Japan. All neonates developed irreversible multiple-organ failure and died.
View Article and Find Full Text PDFSubsequent bacteremia developed in 14 % of patients with positive catheter tip cultures but concurrent negative blood cultures. The occurrence of subsequent bacteremia did not differ significantly by pathogens (Staphylococcus aureus, Gram-negative rods [GNR], and Candida spp.).
View Article and Find Full Text PDFArticle Synopsis
- * It highlights the complexities of performing allogeneic transplants amid active infections, as they typically have poor outcomes.
- * A specific case is presented about a 5-year-old boy with disseminated infection who received granulocyte transfusions from his mother and underwent successful haploidentical stem cell transplantation from his father after immunosuppressive treatment for SAA.
Purpose: Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear.
Methods: Studying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs.
Article Synopsis
- HLA-haploidentical stem cell transplantation (haplo-SCT) using post-transplant high-dose cyclophosphamide (PT-CY) is typically an alternative for patients without suitable donors, but it's risky for those with Fanconi anemia (FA).
- For FA patients, αβT-cell and B-cell depletion (αβT/B-depleted haplo-SCT) is preferred to lower the chances of complications from PT-CY and graft-versus-host disease (GVHD).
- In a case study, an 11-year-old boy with FA successfully received αβT/B-depleted haplo-SCT from his father, achieving neutrophil engraftment by day 9 and remaining healthy without GV
Prognostic and Pharmacotypic Heterogeneity of Hyperdiploidy in Childhood ALL.
J Clin Oncol
December 2023
Article Synopsis
- * Researchers analyzed data from 1,096 patients using various definitions of hyperdiploidy to assess the best predictors for event-free survival (EFS) and relapse rates; findings indicated that the DNA index (DI1.16-1.6) was the most favorable criterion.
- * The results highlight that hyperdiploidy and certain subgroups respond well to specific drugs, with distinct sensitivities to asparaginase and mercaptopurine based on particular chromosomal traits, suggesting a more personalized approach to treatment for
Article Synopsis
- Hemophagocytic lymphohistiocytosis (HLH) is a serious and potentially fatal condition that presents with symptoms like fever, low blood cell counts, and spleen enlargement, often triggered by infections, cancers, or autoimmune disorders.
- A 12-year-old girl developed HLH one day after receiving both the SARS-CoV-2 and influenza vaccines, showing clear symptoms like fever and splenomegaly.
- After diagnosing HLH 12 days post-vaccination and ruling out other causes, the patient responded well to treatment with oral prednisolone, highlighting the need for early diagnosis in similar vaccine-associated cases.
Article Synopsis
- Resistance to chemotherapy in acute lymphoblastic leukemia (ALL) is a significant reason for treatment failure, with challenges in current testing methods for drug sensitivity.
- A new fluorescence imaging method allows for efficient profiling of drug sensitivity in primary ALL cells using co-culture with stromal cells and a panel of 40 drugs, aiming to identify individual resistance patterns.
- This automated approach enhances testing efficiency by needing fewer cells and reduces the labor and time required, integrating drug sensitivity data with genomic profiling for a more precise treatment strategy.
LCK is a novel therapeutic target in ~40% of T-cell acute lymphoblastic leukemia (T-ALL), and dasatinib and ponatinib can act as LCK inhibitors with therapeutic effects. We herein report a comprehensive preclinical pharmacokinetic and pharmacodynamic evaluation of dasatinib and ponatinib in LCK-activated T-ALL. In 51 human T-ALL cases, these two drugs showed similar patterns of cytotoxic activity, with ponatinib being slightly more potent.
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- Mixed lineage leukemia 1-rearranged (MLL1-r) acute leukemia patients have poor treatment responses, necessitating the development of therapies that disrupt the Menin-MLL1 complex, such as the compound DS-1594a.
- Preclinical evaluations showed that DS-1594a and its salts effectively inhibited the growth of MLL1-r or NPM1c leukemic cells, outperforming traditional chemotherapy like cytrabine in in vitro and in vivo models.
- DS-1594a, with its potent antitumor effects, suggests potential as a new oral anticancer therapy, distinct from existing treatments, offering hope for improved outcomes in acute leukemia patients.
Cord Blood Transplantation in 2 Infants Presenting Monosomy 7 Clonal Hematopoiesis: SAMD9 / SAMD9L Germline Mutation.
J Pediatr Hematol Oncol
March 2023
Article Synopsis
- Germline mutations in the SAMD9 and SAMD9L genes have been linked to monosomy 7 in children.
- Two infants with these mutations showed serious health issues, including anemia and thrombocytopenia in one, and neutropenia with brain complications in the other.
- Both infants underwent cord blood transplantation but faced severe complications like engraftment syndrome and life-threatening graft-versus-host disease, along with loss of chromosome 7 in their bone marrow cells.
Contemporary chemotherapy for childhood acute lymphoblastic leukemia (ALL) is risk-adapted based on clinical features, leukemia genomics and minimal residual disease (MRD); however, the pharmacological basis of these prognostic variables remains unclear. Analyzing samples from 805 children with newly diagnosed ALL from three consecutive clinical trials, we determined the ex vivo sensitivity of primary leukemia cells to 18 therapeutic agents across 23 molecular subtypes defined by leukemia genomics. There was wide variability in drug response, with favorable ALL subtypes exhibiting the greatest sensitivity to L-asparaginase and glucocorticoids.
View Article and Find Full Text PDFMonogenic inflammatory bowel disease with STXBP2 mutations is not resolved by hematopoietic stem cell transplantation but can be alleviated via immunosuppressive drug therapy.
Clin Immunol
January 2023
Article Synopsis
- STXBP2 is a gene linked to intracellular trafficking and is associated with familial hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD), but its exact impact is still not fully understood.
- A novel mutation in STXBP2 was found in a boy suffering from severe diarrhea and HLH, who underwent a series of treatments including stem cell transplantation.
- Despite treatments alleviating some symptoms, the patient continued to experience mild colitis and persistent diarrhea, indicating that STXBP2-related IBD may involve both excessive inflammation and issues with the gut's protective barrier.
Article Synopsis
- - X-linked lymphoproliferative disease type 1 (XLP1) is a rare immune disorder caused by a deficiency of SAP, leading to severe complications like hemophagocytic lymphohistiocytosis or, in rare cases, limbic encephalitis without EBV infection.
- - A case involving a 12-year-old boy diagnosed with limbic encephalitis showcased severe symptoms, including seizures and cognitive deficits; treatments were ineffective, leading to his death, and genetic testing identified a new mutation.
- - The study suggests that the immune dysregulation in XLP1 may lead to the production of anti-AMPAR autoantibodies, potentially causing limbic encephalitis, indicating that specific B-cell
Understanding the genomic and epigenetic mechanisms of drug resistance in pediatric acute lymphoblastic leukemia (ALL) is critical for further improvements in treatment outcomes. The role of transcriptomic response in conferring resistance to l-asparaginase (LASP) is poorly understood beyond asparagine synthetase (ASNS). We defined reproducible LASP response genes in LASP-resistant and LASP-sensitive ALL cell lines as well as primary leukemia samples from newly diagnosed patients.
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- Epigenetic changes, like histone acetylation, play a key role in the cancer progression and development of chemotherapy resistance in blood cells, presenting new treatment avenues.
- Panobinostat, an FDA-approved drug for multiple myeloma, shows promise against acute lymphoblastic leukemia (ALL) but faces challenges due to undefined resistance mechanisms.
- Researchers used CRISPR technology to discover that increased mitochondrial activity drives resistance to panobinostat in ALL, and higher levels of the protein SIRT1 can predict better responses to the drug, suggesting that combining treatments targeting SIRT1 may enhance effectiveness.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many high-risk pediatric hematological malignant diseases (MD) and several nonmalignant diseases (NMD), including primary immune deficiencies. Infections must be managed to obtain better outcomes after HSCT. In this prospective observational study, viral monitoring was performed on 74 pediatric patients with MD and NMD who underwent HSCT.
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- T-cell acute lymphoblastic leukemia (T-ALL) is a serious blood cancer that shows varying drug responses, with about 44% of children and 17% of adults responding well to the drug dasatinib.
- Research found that the activation of a specific signaling pathway (preTCR-LCK) is key to why some T-ALL cases are sensitive to dasatinib, while other cases are resistant to a different drug called venetoclax.
- The study highlights that the developmental stage of T-cells in leukemia influences which signaling pathways are active, suggesting potential for developing targeted therapies based on a patient's specific leukemia characteristics.
Article Synopsis
- Research identified 463 genomic features linked to glucocorticoid resistance in acute lymphoblastic leukemia using a comprehensive analysis of mRNA, miRNA, and other genetic factors.
- A total of 118 overlapping genes were found, including 30 out of 38 known glucocorticoid-resistance genes, along with 14 new genes connected to resistance.
- The study highlighted CELSR2 as a significant player in glucocorticoid resistance, leading to the discovery of a potential new drug combination that could combat resistance in leukemia treatments.