ABSTRACT
INTRODUCTION: Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS: We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression. RESULTS: A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS: In this study, MI-positive cases had a worse prognosis compared with MI-negative cases. PREVIOUS PRESENTATIONS: No portion of this study has been presented or published previously.
Subject(s)
Brain Neoplasms , Glioma , Humans , Male , Child , Young Adult , Adult , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Histones/genetics , Mutation , Glioma/diagnostic imaging , Glioma/genetics , PrognosisABSTRACT
OBJECTIVE: This study primarily focused on the diagnostic interval (DI), defined as the duration from the onset of leukemic symptoms to diagnosis. We investigated whether a prolonged DI is associated with the outcomes of pediatric leukemia. METHODS: We retrospectively collected data of children with newly diagnosed pediatric leukemia at Okayama University Hospital from January 2007 to December 2022. Survival analyses were conducted using Kaplan-Meier methods, and an unadjusted analysis to compare differences in survival was performed using the log-rank test. RESULTS: In total, 103 children with leukemia were included in the analysis. The median DI was 20 days (interquartile range, 9.5-33.5 days). A prolonged DI (≥30 days) demonstrated no association with either 5-year event-free survival (70.1% for <30 days and 68.3% for ≥30 days, p = .99, log-rank test) or overall survival (84.7% for <30 days and 89.4% for ≥30 days, p = .85, log-rank test). CONCLUSIONS: A prolonged DI was not associated with the survival of children with leukemia. If a precise classification of leukemia biology is provided for pediatric patients, a prolonged DI may have little impact on the prognosis of these patients.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Retrospective Studies , Prognosis , Survival Analysis , Progression-Free SurvivalABSTRACT
A three-year-old boy with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+ALL) presented with an osteolytic lesion in his right upper arm. Tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib are an essential component throughout the course of treatment for Ph+ALL. However, TKIs are reported to affect the bone metabolism. In the treatment course of the current patient, the osteolytic lesion quickly improved despite the continuous use of TKIs, even during the concomitant use of corticosteroids. This suggests that TKIs can be safely given with concomitant corticosteroids to children with Ph+ALL, even when osteolytic lesions are present.
Subject(s)
Lymphoma, Non-Hodgkin , Osteolysis , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Male , Child , Humans , Child, Preschool , Osteolysis/drug therapy , Osteolysis/etiology , Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapyABSTRACT
BACKGROUND: Granulocyte transfusion therapy is a rational therapeutic option for patients with prolonged, severe neutropenia. Although high molecular weight hydroxyethyl starch (hHES) facilitates the separation of red blood cells during granulocyte collection, renal dysfunction has been noted as a potential side effect. HES130/0.4 (Voluven®) is a medium molecular weight HES (mHES) with superior safety profiles compared to hHES. Although HES130/0.4 is reportedly effective in the collection of granulocytes, we lack studies comparing the efficiency of granulocyte collection using HES130/0.4 and hHES. STUDY DESIGN AND METHODS: We retrospectively collected the data from 60 consecutive apheresis procedures performed on 40 healthy donors at the Okayama University Hospital between July 2013 and December 2021. All procedures were performed using the Spectra Optia system. Based on the HES130/0.4 concentration in the separation chamber, granulocyte collection methods using HES130/0.4 were classified into m0.46, m0.44, m0.37, and m0.8 groups. We used HES130/0.4 and hHES groups to compare the various sample collection methods. RESULTS: The median granulocyte collection efficiency (CE) was approximately 24.0% and 28.1% in the m0.8 and hHES groups, respectively, which were significantly higher than those in the m0.46, m0.44, and m0.37 groups. One month following granulocyte collection with HES130/0.4, no significant changes were observed in serum creatinine levels compared to those before the donation. CONCLUSION: Therefore, we propose a granulocyte collection approach employing HES130/0.4, which is comparable to the use of hHES in terms of the granulocyte CE. A high concentration of HES130/0.4 in the separation chamber was considered crucial for granulocyte collection.
Subject(s)
Blood Component Removal , Neutropenia , Humans , Molecular Weight , Retrospective Studies , Granulocytes , Hydroxyethyl Starch DerivativesABSTRACT
In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases.
Subject(s)
Brain Neoplasms , Glioma , Male , Humans , Child , Adolescent , Temozolomide , Mutation , Glioma/diagnosis , Glioma/genetics , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Brain Neoplasms/pathology , GenomicsABSTRACT
Among patients with transient abnormal myelopoiesis (TAM) associated with Down syndrome, approximately 20% die within 6 months from multiorgan failure, especially liver fibrosis. We experienced three children with TAM who had low white blood cell counts but increased bilirubin levels. Here, we discuss the detailed clinical courses of these patients, including the pathological findings of liver biopsies. Our cases, together with previous literature, suggest that liver biopsy can be performed safely and provides useful information, especially regarding disease activities, and that low-dose cytarabine is a reasonable option to prevent early death in TAM patients with liver dysfunction.
Subject(s)
Down Syndrome , Child , Humans , Down Syndrome/complications , Cytarabine , Liver , BiopsySubject(s)
Leukemia, Myeloid, Acute , Child , Humans , Leukemia, Myeloid, Acute/therapy , Aniline Compounds , Pyrazines , fms-Like Tyrosine Kinase 3 , MutationABSTRACT
BACKGROUND: Neonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with εγδß-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation. CASE PRESENTATION: A 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with εγδß-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation. CONCLUSIONS: We reported that an infant with εγδß-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia.
Subject(s)
Iron Overload , Liver Transplantation , Thalassemia , Male , Infant , Infant, Newborn , Humans , Hepcidins , Liver Transplantation/adverse effects , Erythropoiesis , Living Donors , Iron Overload/genetics , IronABSTRACT
BACKGROUND: Varicella-zoster virus (VZV) reactivation is a serious complication of hematopoietic stem cell transplantation (HSCT). Although low-dose acyclovir can prevent VZV reactivation after HSCT in adults, the efficacy of a dose of acyclovir lower than the recommended dose, such as 60-80 mg/kg/day in children, is unclear. In this study, we aimed to evaluate the incidence of VZV reactivation after HSCT during and after low-dose acyclovir administration for preventing VZV reactivation in children. METHODS: This single-center retrospective study included children aged ≤15 years who received oral acyclovir (at 15 mg/kg/day) to prevent VZV reactivation after HSCT. We examined the cumulative incidence of VZV reactivation after HSCT, during and after prophylactic acyclovir administration. RESULTS: Fifty-three eligible patients were included in this study, of whom 37 underwent allogeneic HSCT. The median duration of prophylactic acyclovir therapy was 264 days (range: 69-1140 days). VZV reactivation occurred in 13 patients (24.5%, 95% confidence interval [CI]: 14.9-37.6). The cumulative incidence of VZV reactivation 1 and 2 years after HSCT was 6.26% (95% CI: 1.60-15.5) and 20.9% (95% CI: 10.3-34.0), respectively. While only one patient developed VZV reactivation during the administration of prophylactic acyclovir, the cumulative incidence of VZV reactivation increased to 24.2% (95% CI: 12.5-38.0) 1 year after the cessation of acyclovir. CONCLUSION: Low-dose acyclovir (15 mg/kg/day) could be effective for preventing VZV reactivation after HSCT in children because VZV reactivation seldom occurs during the administration of 15 mg/kg/day acyclovir.
Subject(s)
Hematopoietic Stem Cell Transplantation , Herpes Zoster , Adult , Child , Humans , Acyclovir/pharmacology , Acyclovir/therapeutic use , Herpesvirus 3, Human/physiology , Retrospective Studies , Herpes Zoster/etiology , Herpes Zoster/prevention & control , Herpes Zoster/drug therapy , Transplantation, Homologous/adverse effects , Virus Activation , Antiviral Agents/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effectsABSTRACT
PURPOSE: Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors. METHODS: We analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes. RESULTS: The median age at diagnosis was 14 years (range 3-82 years) and 4 patients (14%) were elderly (patients ≥ 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis. CONCLUSIONS: Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.
Subject(s)
Astrocytoma , Brain Neoplasms , Humans , Aged , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged, 80 and over , DNA Methylation , Retrospective Studies , Brain Neoplasms/pathology , Mutation , Astrocytoma/pathology , Isocitrate Dehydrogenase/geneticsABSTRACT
BACKGROUND: For pediatric recipients, red blood cells (RBCs) are added to bone marrow (BM) collections before low RBC volume BM processing using COBE Spectra (COBE) or Spectra Optia (Optia). However, the processing efficiency of this approach has not been evaluated. This study aimed to evaluate RBC depletion and nucleated cell subpopulation recovery rates in third-party RBC-manipulated BM products processed with the COBE or Optia. STUDY DESIGN AND METHODS: We retrospectively collected data on RBC depletion from low RBC volume BM with third-party RBCs (manipulated group) and on conventional large-volume, BM (unmanipulated group) processing performed between September 2010 and December 2021. All procedures were performed using COBE or Optia. RESULTS: The median residual RBC volume in the manipulated group was 9.5 ml in COBE and 2.5 ml in Optia (p = .01). The median total nucleated cell (TNC) and mononuclear cell (MNC) were comparable between the manipulated groups using each cell separator (TNC, 40.8 vs. 47.1%; MNC, 78.3 vs. 79.4%). The manipulation did not adversely affect TNC and MNC recoveries in either device. In addition, Optia achieved similar CD34+ cell recovery to that in large-BM-volume processing using the same device (147.5 vs. 184.5%, p = .112). During a follow-up period, neutrophil engraftment was achieved in all patients who received third-party RBC-manipulated grafts, and platelet engraftment was achieved in all cases, except one. CONCLUSION: The addition of third-party RBC to low RBC volume BM collections from or for pediatric patients does not have any negative impact on either RBC depletion or hematopoietic cell recovery during processing with the widely used cell separator.
Subject(s)
Bone Marrow Transplantation , Bone Marrow , Antigens, CD34 , Bone Marrow Transplantation/methods , Child , Erythrocytes , Humans , Retrospective StudiesABSTRACT
The effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on systemic chronic active Epstein-Barr virus infection (sCAEBV) are yet to be analyzed in a large number of patients. Using the Japanese registry database, Transplant Registry Unification Management Program, we investigated the outcomes of 102 sCAEBV patients who underwent allo-HSCT. The median age at HSCT was 21 years, and the three-year overall survival (3-year OS) rate was 72.5%. Of the 90 patients whose viral load after allo-HSCT was evaluated, 56 (62.2%) achieved a virological complete response, defined by the complete resolution of disease activity with a significant decrease in EBV-DNA in peripheral blood. The multivariate Cox proportional hazard model indicated that advanced age, in adolescents and young adults (AYA) (age, 15-39) and adults (age, ≥40 years) was a risk factor of poor OS. The hazard ratios (HRs) of the AYA and adult groups were 10.87 (95% confidence interval [CI]: 1.98-59.56, p = .006) and 15.93 (95% CI: 2.45-103.8, p = .004), respectively. Disease activity (HR 5.74), elevated soluble IL-2 receptor (sIL-2R) (≥ median, 691 U/mL) at HSCT (HR 6.93), and conditioning without radiotherapy (HR 3.53) were also independently associated with poor survival. Notably, 79% of radiotherapy doses were less than 6 Gy. Regardless of the presence of hemophagocytic lymphohistiocytosis, the group with a high sIL-2R level (≥2000 U/mL) showed a poorer prognosis. Although allo-HSCT is the only curative therapy for sCAEBV, treatment strategies need to be improved for high-risk patients, especially those with high levels of sIL-2R.
Subject(s)
Epstein-Barr Virus Infections , Hematopoietic Stem Cell Transplantation , Adolescent , Adult , Data Analysis , Epstein-Barr Virus Infections/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Herpesvirus 4, Human , Humans , Japan/epidemiology , Registries , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: CD34+ cell collection efficiency (CE) is the determining factor when calculating processed blood volume (PBV) for leukapheresis (LP). However, the factors affecting CE in the continuous mononuclear cell collection (cMNC) protocol performed by the Spectra Optia apheresis system are not well established. STUDY DESIGN AND METHODS: We retrospectively collected the data from 147 consecutive apheresis procedures across 106 healthy donors and 27 patients completed between July 2016 and December 2020 at the Okayama University Hospital. All procedures were performed using the Optia cMNC protocol. RESULTS: The median CD34+ CE2 was significantly higher in the donor samples (64.3%) than in the patient samples (46.8%) (p < .0001). WBC counts, hematocrit, and platelet counts were all significantly higher in the donors than in the patients, and there was a moderate positive correlation between CD34+ CE2 and hematocrit (r = .47, p < .0001), with the equation of the line being y = 1.23x + 12.23. In contrast, there was only a very weak correlation between CD34+ CE2 and WBC or platelet count. In addition, low hematocrit correlated with an increased time to interface formation. CONCLUSION: These data revealed the negative impact of low hematocrit on the efficiency of CD34+ cell collection when using the Optia cMNC protocol and suggest that hematocrit values should also be considered when determining PBV.
Subject(s)
Blood Component Removal , Hematopoietic Stem Cell Mobilization , Antigens, CD34 , Blood Component Removal/methods , Hematocrit , Hematopoietic Stem Cell Mobilization/methods , Humans , Leukapheresis/methods , Leukocytes, Mononuclear , Retrospective StudiesABSTRACT
Polymorphisms in methotrexate transporter pathways have been associated with methotrexate toxicities and clearance. Recent genome-wide association studies have revealed that the SLCO1B1 T521C variant is associated with methotrexate elimination. We present a case of a pediatric patient with acute lymphoblastic leukemia who suffered from persistently high plasma methotrexate concentrations and acute kidney injuries after the admin-istration of a medium dose of methotrexate. Subsequent genetic analysis showed that he was a carrier of dys-functional genetic variants associated with methotrexate clearance. This case highlights that polymorphisms of methotrexate transporter pathways can adversely affect methotrexate elimination in a clinically significant manner.
Subject(s)
Antimetabolites, Antineoplastic/pharmacokinetics , Methotrexate/pharmacokinetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/blood , Child , Humans , Liver-Specific Organic Anion Transporter 1 , Male , Methotrexate/administration & dosage , Methotrexate/blood , Methylenetetrahydrofolate Reductase (NADPH2) , Polymorphism, Single Nucleotide/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/geneticsABSTRACT
RATIONALE: Growing teratoma syndrome is defined as an increase in tumor size during or after systemic chemotherapy for germ cell tumors. These cases involve normal tumor maker levels and histological features of only mature teratoma. We report a rare case of an ovarian immature teratoma in a Japanese child that was diagnosed as growing teratoma syndrome. PATIENT CONCERNS: A 12-year-old girl presented a painful abdominal mass. She underwent left salpingo-oophorectomy for grade 1 immature teratoma in the left ovary. She did not undergo additional chemotherapy or radiotherapy. Four months later, she presented with grade 3 immature teratoma disseminated into the abdomen and pelvis. Chemotherapy resulted in the tumor maker levels returning to their normal ranges, although the tumors had grown slightly. DIAGNOSIS: The specimens resected by laparotomy after the chemotherapy consisted of mature tissue predominantly, although primitive neuroepithelium was observed in a small part of the specimen. The pathological diagnosis was grade 1 immature teratoma, notwithstanding the clinical diagnosis was growing teratoma syndrome based on the clinical features and pathogenesis. INTERVENTIONS: Laparotomy was performed at 7 months after the first operation, with resection of various tumors as well as the rectum, sigmoid colon, residual left fallopian duct, and a small part of the ileum and omentum. Some small tumors at the parietal peritoneum were ablated, although many tiny tumors around the uterus were left untreated. OUTCOMES: The patient has been free from recurrence for 5 years. LESSONS: Growing teratoma syndrome can develop in children, and their tumor size is comparable to that in adolescents and adults. Furthermore, development of growing teratoma syndrome from a primary germ cell tumor is presumably faster in children than in adolescents and adults. Complete resection of all growing teratoma tissue is recommended, although fertility-sparing surgery should be considered when possible.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ovarian Neoplasms/therapy , Salpingo-oophorectomy/methods , Teratoma/therapy , Bleomycin/therapeutic use , Child , Cisplatin/therapeutic use , Etoposide/therapeutic use , Female , Humans , Neoplasm Grading , Neoplasm Recurrence, Local , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/pathology , Positron Emission Tomography Computed Tomography , Syndrome , Teratoma/diagnostic imaging , Teratoma/pathologyABSTRACT
BACKGROUND: Tacrolimus is converted from intravenous to oral formulation for the prophylaxis of graft-versus-host disease when patients can tolerate oral intake and graft-versus-host disease is under control. Oral tacrolimus formulation presents poor bioavailability with intraindividual and interindividual variations; however, some factors affecting its blood concentration among pediatric hematopoietic stem cell transplantation (HCT) recipients are still unclear. This study aimed to identify the clinical factors affecting tacrolimus blood concentrations after switching its formulation. METHODS: Changes in the blood concentration/dose ratio (C/D) of tacrolimus in pediatric HCT recipients were analyzed after the switching of tacrolimus from intravenous to oral formulation. Clinical records of 57 pediatric patients who underwent allogenic HCT from January 2006 to April 2019 in our institute were retrospectively reviewed. The C/D of tacrolimus before discontinuation of intravenous infusion (C/Div) was compared with the tacrolimus trough level within 10 days after the initiation of oral administration (C/Dpo). Multiple linear regression analysis was performed to identify factors affecting (C/Dpo)/(C/Div). RESULTS: The constant coefficient of (C/Dpo)/(C/Div) was 0.1692 [95% confidence interval (CI), 0.137-0.2011]. The concomitant use of voriconazole or itraconazole and female sex were significant variables with a beta coefficient of 0.0974 (95% CI, 0.062-0.133) and -0.0373 (95% CI, -0.072 to -0.002), respectively. CONCLUSIONS: After switching of tacrolimus formulation, pediatric HCT recipients might need oral tacrolimus dose that is 5-6 and 3.5-4.5 times the intravenous dose to maintain tacrolimus blood concentrations and area under the concentration-time curve, respectively. With the concomitant use of voriconazole or itraconazole, an oral tacrolimus dose of 4-5 times the intravenous dose seemed appropriate to maintain blood tacrolimus concentration.