Tandem autologous stem cell transplantation in elderly patients with myeloma: A multicenter retrospective analysis.

Tandem autologous stem cell transplantation (ASCT) has been reconsidered for high-risk patients with myeloma, and the eligibility criteria for up-front ASCT have been updated to include more elderly patients. This study aimed to evaluate the efficacy and tolerability of tandem ASCT in elderly patients with myeloma compared to tandem ASCT in young patients and single ASCT in elderly patients. A retrospective study using the Transplant Registry Unified Management Program database of the Japanese Society for Transplantation and Cellular Therapy, which included 64 elderly and 613 young patients who received tandem ASCT, and 891 elderly patients who received single ASCT, was conducted.

Final efficacy and safety results and biomarker analysis of a phase 2 study of cabozantinib in Japanese patients with advanced renal cell carcinoma.

Background: Cabozantinib was established as the standard of care for the treatment of patients with renal cell carcinoma (RCC) whose disease had progressed after vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy in the global randomized trial METEOR. A phase 2 study was conducted to bridge the findings in METEOR to Japanese patients. Here, we report a biomarker analysis and update the efficacy and safety results of cabozantinib treatment.

Psychometrics of the kiddie schedule for affective disorders and schizophrenia present and lifetime version for DSM-5 in Japanese outpatients.

Objective: The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) is a widely used semi-structured diagnostic interview in child and adolescent psychiatry. However, the psychometric properties of its updated version, the K-SADS-PL for DSM-5, have scarcely been examined, especially for criterion validity. This study was designed to examine the inter-rater reliability, criterion validity and construct validity of the K-SADS-PL for DSM-5 in 137 Japanese outpatients.

Stromal Reprogramming through Dual PDGFRα/β Blockade Boosts the Efficacy of Anti-PD-1 Immunotherapy in Fibrotic Tumors.

Unlabelled: Excess stroma and cancer-associated fibroblasts (CAF) enhance cancer progression and facilitate immune evasion. Insights into the mechanisms by which the stroma manipulates the immune microenvironment could help improve cancer treatment. Here, we aimed to elucidate potential approaches for stromal reprogramming and improved cancer immunotherapy.

Trametinib improves Treg selectivity of anti-CCR4 antibody by regulating CCR4 expression in CTLs in oral squamous cell carcinoma.

Regulatory T-cells (Tregs) play a major role in suppressing anti-tumor immune responses. Mogamulizumab, an anti-CC chemokine receptor type 4 (CCR4) monoclonal antibody, depletes effector Tregs (eTregs). However, the clinical efficacy of mogamulizumab was limited in phase Ia/Ib studies for solid tumors (NCT01929486); the finding suggests that mogamulizumab may also deplete beneficial CCR4CD8 T-cells in patients.

Hypercholesterolemic Dysregulation of Calpain in Lymphatic Endothelial Cells Interferes With Regulatory T-Cell Stability and Trafficking.

Background: Although hypercholesterolemia reportedly counteracts lymphocyte trafficking across lymphatic vessels, the roles of lymphatic endothelial cells (LECs) in the lymphocyte regulations remain unclear. Previous studies showed that calpain-an intracellular modulatory protease-interferes with leukocyte dynamics in the blood microcirculation and is associated with hypercholesterolemic dysfunction in vascular endothelial cells.

Methods: This study investigated whether the calpain systems in LECs associate with the LEC-lymphocyte interaction under hypercholesterolemia using gene-targeted mice.

Novel risk assessment for the intensity of conditioning regimen in older patients.

Reduced-intensity conditioning (RIC) regimens have long-term outcomes that are generally comparable with those of myeloablative conditioning (MAC) because of a lower risk of nonrelapse mortality (NRM) but a higher risk of relapse. However, it is unclear how we should select the conditioning intensity in individual cases. We propose the risk assessment for the intensity of conditioning regimen in elderly patients (RICE) score.

Quantitative Evaluation of Changes in Three-Dimensional CT Density Distributions in Pulmonary Alveolar Proteinosis after GM-CSF Inhalation.

Background: A previous clinical trial for autoimmune pulmonary alveolar proteinosis (APAP) demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation reduced the mean density of the lung field on computed tomography (CT) across 18 axial slice planes at a two-dimensional level. In contrast, in this study, we challenged three-dimensional analysis for changes in CT density distribution using the same datasets.

Methods: As a sub-study of the trial, CT data of 31 and 27 patients who received GM-CSF and placebo, respectively, were analyzed.

Serum Soluble Fas Levels and Incidence of Liver Cancer in Nested Case-Control Study.

Background: Soluble Fas (sFas) plays various roles in carcinogenesis and tumor dissemination by preventing apoptosis via binding to Fas ligand. We analyzed associations of serum sFas levels with the incidence of liver cancer in a prospective case-control study nested in the Japan Collaborative Cohort Study.

Methods: A baseline survey was conducted from 1988, with blood samples obtained from 39,242 subjects.

The Effects of the Great East Japan Earthquake on Perinatal Outcomes: Results of the Pregnancy and Birth Survey in the Fukushima Health Management Survey.

There are limited studies on the long-term effects of natural/environmental disasters, especially nuclear disasters, on obstetric outcomes. This study aimed to review the results of perinatal outcomes immediately after the Great East Japan Earthquake (GEJE) and the Fukushima Daiichi Nuclear Power Plant accident, as well as their long-term trends over 8 years, in the Fukushima Health Management Survey. The annual population-based Pregnancy and Birth Survey is conducted as part of the Fukushima Health Management Survey.

Effects of External Radiation Exposure on Perinatal Outcomes in Pregnant Women After the Fukushima Daiichi Nuclear Power Plant Accident: the Fukushima Health Management Survey.

Background: This study aimed to investigate the effects of maternal exposure to external radiation on perinatal outcomes among women who experienced the Fukushima Daiichi Nuclear Disaster (FDND) using the Fukushima Health Management Survey (FHMS).

Methods: Data from the Pregnancy and Birth Survey and Basic Survey in the FHMS were combined to analyze external maternal radiation exposure following the FDND, and the relationship between radiation dose and perinatal outcomes was analyzed using binomial logistic regression analysis. Missing dose data were supplemented using multiple imputation.

Construction of a T cell receptor signaling range for spontaneous development of autoimmune disease.

Thymic selection and peripheral activation of conventional T (Tconv) and regulatory T (Treg) cells depend on TCR signaling, whose anomalies are causative of autoimmunity. Here, we expressed in normal mice mutated ZAP-70 molecules with different affinities for the CD3 chains, or wild type ZAP-70 at graded expression levels under tetracycline-inducible control. Both manipulations reduced TCR signaling intensity to various extents and thereby rendered those normally deleted self-reactive thymocytes to become positively selected and form a highly autoimmune TCR repertoire.

Risk factors for fatal cardiac complications after allogeneic hematopoietic cell transplantation: Japanese Society for Transplantation and Cellular Therapy transplant complications working group.

Fatal cardiac complications can occur from the early to late phases after hematopoietic cell transplantation (HCT). Herein, the Japanese transplant registry database was used to retrospectively analyze health records of 33,791 allogeneic HCT recipients to elucidate the pathogenesis and risk factors involved. Overall, 527 patients died of cardiac complications at a median of 130 (range 0-3924) days after HCT.

Outcome of peripheral blood stem cell transplantation from HLA-identical sibling donors for adult patients with aplastic anemia.

Although bone marrow transplantation is the recommended form of allogeneic hematopoietic stem cell transplantation for aplastic anemia, some patients undergo peripheral blood stem cell transplantation (PBSCT). Therefore, there is critical demand to identify factors affecting transplantation outcomes. Using the Japanese registry database, we retrospectively analyzed outcomes of 94 adult patients with aplastic anemia who underwent PBSCT from HLA-identical sibling donors.

Differential properties of KRAS transversion and transition mutations in non-small cell lung cancer: associations with environmental factors and clinical outcomes.

Background: KRAS-mutated non-small cell lung cancer (NSCLC) accounts for 23-35% and 13-20% of all NSCLCs in white patients and East Asians, respectively, and is therefore regarded as a major therapeutic target. However, its epidemiology and clinical characteristics have not been fully elucidated because of its wide variety of mutational subtypes. Here, we focused on two distinct base substitution types: transversion mutations and transition mutations, as well as their association with environmental factors and clinical outcome.

Efficacy of transcatheter arterial embolization for first-line treatment of colonic diverticular bleeding with extravasation on contrast-enhanced computed tomography.

Colonic diverticular bleeding (CDB) is the most frequent cause of acute lower gastrointestinal bleeding. The aim of this study was to evaluate the efficacy and safety of transcatheter arterial embolization (TAE) for CDB as first-line treatment with extravasation on contrast-enhanced computed tomography (CECT), compared with endoscopic hemostasis. Three Japanese institutions participated in this retrospective cohort study.

Functional inhibition of MEF2 by C/EBP is a possible mechanism of leukemia development by CEBP-IGH fusion gene.

CEBPA-IGH, a fusion gene of the immunoglobulin heavy-chain locus (IGH) and the CCAAT enhancer-binding protein α (C/EBPα) gene, is recurrently found in B-ALL cases and causes aberrant expression of C/EBPα, a master regulator of granulocyte differentiation, in B cells. Forced expression of C/EBPα in B cells was reported to cause loss of B-cell identity due to the inhibition of Pax5, a master regulator of B-cell differentiation; however, it is not known whether the same mechanism is applicable for B-ALL development by CEBPA-IGH. It is known that a full-length isoform of C/EBPα, p42, promotes myeloid differentiation, whereas its N-terminal truncated isoform, p30, inhibits myeloid differentiation through the inhibition of p42; however, the differential role between p42 and p30 in ALL development has not been clarified.

Cigarette Smoking, Smoking Cessation, and Bladder Cancer Risk: A Pooled Analysis of 10 Cohort Studies in Japan.

Background: Although cigarette smoking is an established risk factor for bladder cancer, assessment of smoking impact on bladder cancer in Asian populations has been hindered by few cohort studies conducted in Asian populations. Therefore, we investigated the risk of bladder cancer associated with smoking status, cumulative smoking intensity, and smoking cessation in Japan.

Methods: We analyzed data for 157,295 men and 183,202 women in 10 population-based cohort studies in Japan.

Intensified conditioning regimens improved disease-free survival and engraftment after unrelated single-unit cord blood transplantation but not after matched sibling or matched unrelated donor allogeneic hematopoietic cell transplantation.

The impact of conditioning intensity on different donor groups has been unclear in allogeneic transplantation. The objective of this study was to clarify the effect of conditioning intensity on disease-free survival (DFS), relapse, non-relapse mortality (NRM), neutrophil engraftment, and graft-versus-host disease for each donor type. We retrospectively evaluated the effect of conditioning intensity on transplant outcomes for patients with acute leukemia or myelodysplastic syndrome aged between 16 and 60 years in Japan using the transplant conditioning intensity (TCI) scoring system.