Seiji Kojima

Seiji Kojima
Nagoya University | Meidai · Department of Pediatrics

MD,PhD

About

715
Publications
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Publications

Publications (715)
Article
Central venous catheters (CVCs) are essential devices in the treatment of pediatric patients with hematological and oncological disorders; however, the most suitable type of CVC for these patients remains unclear. We retrospectively compared risk factors for unplanned removal of two commonly used CVCs, peripherally inserted central catheters (PICCs...
Preprint
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by heterozygous germline mutations in the fumarate hydratase (FH) gene and is associated with increased susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). This report describes a seven-year-old male who developed a large right kidney tumor wit...
Article
Full-text available
Background: Patients with primary refractory and relapsed neuroblastoma have a poor prognosis since safe and effective chemotherapies for these patients are currently limited. The development of new chemotherapy regimens for these patients is imperative to improve survival outcomes. Methods: We retrospectively analyzed 40 patients with refractor...
Article
Full-text available
The identification of causative genetic variants for hereditary diseases has revolutionized clinical medicine and an extensive collaborative framework with international cooperation has become a global trend to understand rare disorders. The Initiative on Rare and Undiagnosed Diseases (IRUD) was established in Japan to provide accurate diagnosis, d...
Article
Diamond-Blackfan anaemia (DBA) shares clinical features with two recently reported sporadic cases of dyserythropoietic anaemia with a cryptic GATA1 splicing mutation (c.871-24 C>T). We hypothesized that some patients clinically diagnosed with DBA but whose causative genes were unknown may carry the intronic GATA1 mutation. Here, we examined 79 pati...
Article
In 2008, the World Health Organization proposed a new entity of childhood myelodysplastic syndrome (MDS), which was referred to as refractory cytopenia of childhood (RCC). However, whether this morphological classification reflects clinical outcomes remains unclear. We performed a prospective evaluation of bone marrow morphology in 252 children wit...
Article
Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative neoplasm that develops during infancy and early childhood. The array-based international consensus definition of DNA methylation has recently classified patients with JMML into the following three groups: high methylation (HM), intermediate methylation (IM), and lo...
Article
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by heterozygous germline variants in the fumarate hydratase (FH) gene and is associated with increased susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). HLRCC-associated RCC usually occurs in the middle age, with the median age being 40–44 ye...
Article
Full-text available
Pediatric solid tumors are a heterogeneous group of neoplasms with over 100 subtypes. Clinical and histopathological diagnosis remains challenging due to the overlapping morphological and immunohistochemical findings and the presence of atypical cases. To evaluate the potential utility of including RNA-sequencing (RNA-seq) in the diagnostic process...
Article
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Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for the hematologic manifestations of Diamond-Blackfan anemia (DBA). However, data regarding the optimal conditioning regimen for DBA patients are limited. We retrospectively compared the outcomes of DBA patients who underwent HSCT using either myeloablative cond...
Article
Objectives: Patients with acquired aplastic anemia (AA) without HLA-matched sibling donors or aged >40 years receive immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG). We investigated the relationship between plasma rabbit ATG (r-ATG) concentration and IST response. Methods: From May 2012 to October 2017, 81 patients with severe...
Article
Background : Pulmonary hypertension (PH) is associated with a high morbidity in children receiving hematopoietic stem cell transplantation (HSCT). However, due to the lack of sequential echocardiography, the nature of the condition is not fully understood. Objectives : To study whether routine echocardiography performed after HSCT could detect pat...
Article
Full-text available
The aim of this study was to determine whether human herpesvirus 6B (HHV-6B) infection can impair the hippocampus in pediatric hematopoietic stem cell transplant (HSCT) recipients. Study subjects were pediatric HSCT recipients monitored for HHV-6B infection who underwent brain MRI before and after transplantation. Volumetric analysis of the hippoca...
Article
Background Type I interferonopathies are a recently established subgroup of autoinflammatory diseases caused by mutations in genes associated with proteasome degradation or cytoplasmic RNA and DNA sensing pathways. Objective This study aimed to unveil the molecular pathogenesis of a patient with novel type I interferonopathy, for which no known ge...
Preprint
Full-text available
Objective Central venous catheters (CVCs) have been essential devices for the treatment of children with hematological and oncological disorders. Only few studies investigated the complications and selections of different types of CVCs in these pediatric patients. This study aimed to compare risk factors for unplanned removal of two commonly used C...
Article
We have recently discovered Japanese children with a novel Fanconi anemia-like inherited bone marrow failure syndrome. This disorder is likely caused by the loss of a catabolic system directed toward endogenous formaldehyde, due to biallelic variants in ADH5 combined with a heterozygous ALDH2*2 dominant-negative allele (rs671), which is associated...
Preprint
Background: Patients with relapsed or refractory neuroblastoma have a poor prognosis; there are limited effective and safe rescue chemotherapies for these patients. Development of new chemotherapy regimens for these patients is a key imperative. Procedure: We retrospectively analyzed patients with refractory or relapsed neuroblastoma who received i...
Article
Full-text available
Genetic causes of undiagnosed hemolytic anemia in nineteen patients were analyzed by whole-exome sequencing, and novel COL4A1 variants were identified in four patients (21%). All patients were complicated with congenital malformations of the brain, such as porencephaly or schizencephaly. In these patients, hemolysis became less severe within 2 mont...
Article
Full-text available
Rs671 in the aldehyde dehydrogenase 2 gene ( ALDH2 ) is the cause of Asian alcohol flushing response after drinking. ALDH2 detoxifies endogenous aldehydes, which are the major source of DNA damage repaired by the Fanconi anemia pathway. Here, we show that the rs671 defective allele in combination with mutations in the alcohol dehydrogenase 5 gene,...
Preprint
Background: Central venous catheters (CVCs) have been essential devices for the treatment of children with hematological and oncological disorders. Only few studies investigated the complications and selections of different types of CVCs in these pediatric patients. This study aimed to compare risk factors for unplanned removal of two commonly used...
Conference Paper
BACKGROUND: Inherited bone marrow failure syndromes (IBMFSs) are a heterogeneous group of genetic disorders characterized by bone marrow failure, physical anomalies, and various kinds of organ complications. In addition to classical IBMFSs, such as Fanconi anemia, Diamond-Blackfan anemia, Dyskeratosis congenita, Shwachman-Diamond syndrome, and fami...
Article
Full-text available
Reactive aldehydes arise as by-products of metabolism and are normally cleared by multiple families of enzymes. We find that mice lacking two aldehyde detoxifying enzymes, mitochondrial ALDH2 and cytoplasmic ADH5, have greatly shortened lifespans and develop leukemia. Hematopoiesis is disrupted profoundly, with a reduction of hematopoietic stem cel...
Article
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Background Kawasaki disease (KD) is an idiopathic systemic vasculitis that predominantly damages coronary arteries in children. Various pathogens have been investigated as triggers for KD, but no definitive causative pathogen has been determined. As KD is diagnosed by symptoms, several days are needed for diagnosis. Therefore, at the time of diagno...
Article
Background/aims: Down syndrome associated disorders are caused by a complex genetic context where trisomy 21 is a central component in relation to other changes involving epigenetic regulators and signaling molecules. This unique genetic context is responsible for the predisposition of people with Down syndrome to acute leukemia. Although, the res...
Article
In patients with acquired AA, PGF is a major cause of cytopenia after hematopoietic stem cell transplantation. An increased incidence of PGF, especially sPGF, has been noted after the introduction of the FLU/CY regimen in children with acquired AA. To clarify the risk factors for sPGF, the clinical data of 49 patients (median age, 11 years; range,...
Article
Recently, several studies have been conducted to generate considerable evidence regarding unique treatments for severe aplastic anemia (SAA) in China. Haploidentical donor hematopoietic stem cell transplantation (HID-HSCT) showed an overall survival rate (80.3–86.1%) comparable to those with immunosuppressive therapy (IST) and matched related donor...
Article
Full-text available
Fludarabine/cyclophosphamide-based conditioning regimens are standard in bone marrow transplantation (BMT) for acquired bone marrow failure in children, however, graft failure may occur. Using the data from a nationwide transplantation registry, we compared the outcomes of children aged <16 years with acquired aplastic anemia and refractory cytopen...
Article
Full-text available
Few hematological complications have previously been reported in association with Cri du Chat syndrome (CdCS). A case of myelodysplastic syndromes (MDS) in a pediatric patient with CdCS is herein presented. A 17-year-old female with CdCS caused by ring chromosome 5 was admitted to the hospital for investigation of a 1-month history of anemia. Based...
Article
Introduction: A cryptic form of dyskeratosis congenita (cDKC) has a gradual onset without the characteristic physical findings of DKC. cDKC is distinguished from other forms of bone marrow failure (BMF) through analysis of telomere shortening and gene mutations. Mutations in the telomerase reverse transcriptase (TERT) and telomere RNA component (T...
Conference Paper
Background Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/ myeloproliferative neoplasm that occurs during infancy and early childhood. The clinical course of the disease varies widely. The majority of children require allogenic hematopoietic stem cell transplantation (HSCT) for long term survival, but the disease will eventually...
Article
Background Severe combined immune deficiency (SCID) is a potentially fatal primary immunodeficiency due to the absence of T and B lymphocyte function. Early intervention for patients with SCID results in a higher survival rate. From 2017, we launched the first optional newborn screening (NBS) for SCID in Japan based on the detection of T-cell recep...
Conference Paper
Introduction: Aplastic anemia (AA) is an autoimmune-mediated disease with a complex mechanism. Innate as well as acquired immune system have been considered to participate in its pathogenesis. Although several studies have demonstrated the role of T and B cells in AA, there is limited research focusing on natural killer (NK) cells, which are import...
Article
Background Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myelodysplastic/myeloproliferative disease. Approximately 85% of patients with JMML harbor germline and/or somatic mutations in RAS pathway genes, such as PTPN11, NF1, CBL, NRAS, and KRAS. In a subset of patients with JMML, SETBP1 and JAK3 mutations were identified as secondary...
Article
Background: Human herpesvirus-6B (HHV-6B) infection after allogenic hematopoietic stem cell transplantation (allo-HSCT) is known to be associated with post-transplant limbic encephalitis in adults. Meanwhile, the association between HHV-6B infection and central nervous system complications remains unclear in pediatric allo-HSCT patients. Methods:...
Article
Full-text available
Patients with variants in CUL4B exhibit syndromic intellectual disability (MIM #300354). A seven-year-old boy presented with intellectual disability, a history of seizure, characteristic facial features, and short stature. Whole-exome sequencing detected a c.974+3A>G variant in CUL4B, which was subsequently confirmed to disrupt mRNA splicing. The c...
Article
Full-text available
Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure, predisposition to cancer, and congenital abnormalities. FA is caused by pathogenic variants in any of 22 genes involved in the DNA repair pathway responsible for removing interstrand crosslinks. FANCL, an E3 ubiquitin ligase, is an integral component of the pathway...
Article
Background: Many small for gestational age (SGA) infants have catch-up growth during the first 2 years of life, but approximately 10% have no catch-up growth, and short stature continues into adulthood. Identification of risk factors for absence of catch-up growth at an early age may be useful for earlier diagnosis and earlier treatment. Methods:...
Article
Full-text available
Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes that are involved in rare anemias, due to similarities in the clinica...
Article
Purpose: The presentations and geographic incidence of pediatric non-Hodgkin lymphoma differ from those of adults. This study delineated the characteristics and outcomes of pediatric NHL in East Asia. Material and methods: Medical records of 749 pediatric patients with NHL treated at participating institutions in mainland China, Japan, Korea, an...
Article
Full-text available
We isolated a variant of Chinese pseudorabies virus from a hunting dog with symptoms similar to Aujeszky’s disease and designated the isolate MY-1 strain. The dog developed symptoms 6 days after hunting and biting a wild boar and died the day after onset. The Bam HI restriction profile of MY-1 DNA was different from those of the Japanese reference...
Article
The treatment of choice for patients with severe aplastic anaemia (SAA) includes immunosuppressive therapy (IST) with anti‐thymocyte globulin (ATG) and ciclosporin A. However, the optimal dose for rabbit ATG has yet to be established. We herein report the first prospective, randomized, multicentre study comparing two doses of rabbit ATG in patients...
Article
Childhood leukemia is mostly a ‘‘developmental accident’’ during fetal hematopoiesis and may require multiple prenatal and postnatal ‘‘hits’’. The World Health Organization defines transient leukemia of Down syndrome as increased peripheral blood blasts cells in neonates with Down syndrome and classifies this type of leukemia as a separate entity....
Article
Full-text available
Epstein–Barr virus (EBV) infection is highly prevalent in humans and is implicated in various diseases, including cancer1,2. Chronic active EBV infection (CAEBV) is an intractable disease classified as a lymphoproliferative disorder in the 2016 World Health Organization lymphoma classification1,2. CAEBV is characterized by EBV-infected T/natural ki...
Article
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In the version of this Letter originally published, in the sentence beginning “The major driver role of DDX3X mutations...”, the citation “Fig. 2a–f” should have been “Fig. 2”. In addition, in the sentence beginning “Another finding of interest was the presence of identical driver mutations...”, the citation “Fig. 3a,b and Fig. 4” should have been...
Article
Krüppel-like factor 1 (KLF1), a transcription factor controlling definitive erythropoiesis, is involved in sequential control of terminal cell division and enucleation via fine regulation of key cell cycle regulator gene expression in erythroid lineage cells. Type IV congenital dyserythropoietic anemia (CDA) is caused by a monoallelic mutation at t...
Article
Fanconi anemia is a rare recessive disease characterized by multiple congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancies. It results from mutations in one of the 22 known FANC genes. The number of Japanese Fanconi anemia patients with a defined genetic diagnosis was relatively limited. In this study, we r...
Article
JMML is an aggressive hematopoietic malignancy of early childhood, and allogeneic HSCT is the only curative treatment for this disease. Umbilical cord blood is one of donor sources for HSCT in JMML patients who do not have an HLA‐compatible relative, but engraftment failure remains a major problem. Here, we report two cases of JMML who were success...
Article
Full-text available
Fanconi anemia (FA) is a genetically and clinically heterogeneous disorder that predisposes patients to bone marrow failure (BMF), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). To study which genetic and phenotypic factors predict clinical outcomes for Japanese FA patients, we examined the FA genes, bone marrow karyotype, and a...
Article
Objective: Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome associated with multiple congenital abnormalities and predisposition to malignancies, resulting from mutations in one of the 22 known FA genes (FANCA to W). The proteins encoded by these genes participate in DNA repair pathway (the FA pathway) for endogenous al...
Article
Background: Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure syndrome (IBMFS) characterized by bone marrow failure and pancreatic insufficiency. Patients with SDS have propensity to develop myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Although it is the third most common IBMFS following Fanconi anemia and Dia...
Article
Introduction Epstein-Barr virus (EBV) is a double-stranded DNA virus that infects >95% of the human population and is associated with a substantial risk of cancer development. Most infections in children and adolescents are asymptomatic or result in infectious mononucleosis; however, in some patients, EBV is associated with various hematological ma...
Article
INTRODUCTION Severe combined immunodeficiency disease (SCID) is the most severe form of primary immunodeficiency disorders (PIDs). Impaired cellular and humoral immunity renders the affected infants susceptible to various infections and results in death within the first 2 years of life. Affected infants are asymptomatic at birth, untreated disease...
Article
Introduction: In patients with severe aplastic anemia (SAA) who are not candidates for stem cell transplantation (SCT), immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine A (CyA) is the treatment of choice. A randomized controlled trial demonstrated the inferiority of rabbit ATG compared with horse ATG for first-line...
Article
Full-text available
Genetic mutations account for many devastating early onset immune deficiencies. In contrast, less severe and later onset immune diseases, including in patients with no prior family history, remain poorly understood. Whole exome sequencing in two cohorts of such patients identified a novel heterozygous de novo IKBKB missense mutation (c.607G>A) in t...
Article
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Insertional mutagenesis is an important risk with all genetically modified cell therapies, including chimeric antigen receptor (CAR)-T cell therapy used for hematological malignancies. Here we describe a new tagmentation-assisted PCR (tag-PCR) system that can determine the integration sites of transgenes without using restriction enzyme digestion (...
Article
Full-text available
Inherited bone-marrow-failure syndromes (IBMFSs) include heterogeneous genetic disorders characterized by bone-marrow failure, congenital anomalies, and an increased risk of malignancy. Many lines of evidence have suggested that p53 activation might be central to the pathogenesis of IBMFSs, including Diamond-Blackfan anemia (DBA) and dyskeratosis c...