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BACKGROUND: Myeloablative, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) improves outcome in some high-risk malignant solid tumors and lymphomas in children and young adults. METHODS: We performed 16 peripheral blood stem cell (PBSC) harvests in 12 children and 2 young adult patients with a high-risk malignant solid tumor or refractory/relapsed Hodgkin's lymphoma from August 2015 to December 2020. In our chemotherapy mobilization protocol, we used an absolute neutrophil count (ANC) of >1 × 109/L following the nadir after chemotherapy as the criterion for undertaking the apheresis. RESULTS: The median CD34+ cell count per kg body weight of the 33 apheresis products was 4.92 × 106 cells/kg (range, 0.34-22.53 × 106 cells/kg). Thirteen of the 14 patients (93%) had successful PBSC collections that met their goals for PBSCT. Three patients did not receive PBSCT due to disease progression prior to transplantation. Prompt engraftment occurred in all the remaining 11 patients with 17 PBSCTs. CONCLUSION: Our data suggest that ANC can be helpful as a surrogate parameter in clinical decision-making when the peripheral blood CD34+ count is unavailable.
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BACKGROUND: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive fatal disorder caused by deposition of mutant transthyretin (TTR) amyloids mainly in the nerves and heart. Autonomic dysfunction is a major disabling manifestation, affecting 90% of patients with late-onset ATTRv-PN. The current study aimed to investigate brain functional alterations associated with dysautonomia due to peripheral autonomic nerve degeneration in ATTRv-PN. METHODS: Resting-state functional MRI data were acquired from 43 ATTRv-PN patients predominantly of A97S (p.A117S) genotype, and the functional connectivity of central autonomic regions was assessed. RESULTS: Compared with age-matched healthy controls, the ATTRv-PN patients exhibited (1) reduced functional connectivity of the central autonomic regions such as hypothalamus, amygdala, anterior insula, and middle cingulate cortex with brain areas of the limbic, frontal, and somatosensory systems, and (2) correlations of reduced functional autonomic connectivity with the severity of autonomic dysfunction especially orthostatic intolerance, decreased heart rate variability, and greater clinical disability. CONCLUSIONS: Our findings provide evidence linking peripheral autonomic dysfunction with altered connectivity in the central autonomic network in ATTRv-PN.
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In this study, we investigated the prevalence of mental health problems among patients with cancer and whether oncology nurse navigation improved their mental health outcomes and medical experience. In this randomized controlled clinical trial, we recruited 128 outpatients with cancer via purposive sampling from a teaching hospital in northern Taiwan. Participants were randomly assigned to the navigation group (N = 61) or the usual care group (N = 67). Data were collected from January 2019 to July 2020 using questionnaires, including the self-reported Distress Thermometer, Hospital Anxiety and Depression Scale, Demoralization Scale, and Patient Assessment of Chronic Illness Care. Data were collected at baseline and after three and six months of the intervention. Descriptive and analytical statistical analyses were performed. The prevalence rates of anxiety, depression, distress, and demoralization were 17.9%, 15.7%, 29.7%, and 29.7%, respectively. After three months, the participants in the navigation group exhibited significantly reduced levels of anxiety, demoralization, and emotional distress (reduced by 92%, 75%, and 58%, respectively) and reported a better medical experience (odds ratio = 1.40) than those in the usual care group.
Subject(s)
Neoplasms , Oncology Nursing , Humans , Female , Male , Taiwan , Neoplasms/psychology , Middle Aged , Oncology Nursing/methods , Mental Health , Anxiety , Patient Navigation , Adult , Aged , DepressionABSTRACT
BACKGROUND: The decision to treat children with benign epilepsy with centrotemporal spikes (BECTS) using antiseizure medications (ASM) is controversial. Our goal is to compare the effect of ASM treatment on the alteration of electroencephalographic (EEG) functional connectivity and power across four frequency bands in children with BECTS. METHODS: Children with BECTS with two-year follow-up were retrospectively divided into ASM versus non-ASM groups. The network properties of the EEGs as based on network-based statistic and graph theory were evaluated by the following indices: global efficiency, clustering coefficient, betweenness centrality, and nodal strength in four frequency bands (delta, theta, alpha, and beta). EEG power including absolute power (AP) and relative power (RP) was analyzed in four frequency bands. RESULTS: In children with BECTS with ASM treatment, there was no significant change in EEG connectivity across all bands before and after two years of ASM. In children with BECTS without ASM treatment, there was a significant increase of global efficiency, clustering coefficient, and nodal strength but not the betweenness centrality in the delta band after two years of follow-up. A decrease in AP in the delta and theta bands and a decrease in RP in the theta band were found in the ASM group after two years of treatment. CONCLUSIONS: Our results suggest that ASM may play a role in modulating the development of increasing overall brain connectivity and in downregulating overt synaptic activity, but not intrinsic focal connectivity, in the early years of BECTS. The changes in the EEG power indicate that ASM significantly normalized slow-wave band power.
Subject(s)
Anticonvulsants , Electroencephalography , Epilepsy, Rolandic , Humans , Epilepsy, Rolandic/drug therapy , Epilepsy, Rolandic/physiopathology , Female , Child , Male , Anticonvulsants/pharmacology , Retrospective Studies , Child, Preschool , Follow-Up Studies , Brain Waves/drug effects , Brain Waves/physiology , Nerve Net/drug effects , Nerve Net/physiopathology , Brain/physiopathology , Brain/drug effectsABSTRACT
BACKGROUND: Neuroblastoma varies widely in risk. Risk indicators in infants with incidental neuroblastoma refine treatment confidence for observation or intervention. The potential of functional imaging, particularly PET/CT, remains to be defined. PROCEDURE: A retrospective review of infants under 18 months diagnosed with incidental neuroblastoma from 2008 to May 2022 in our institute was conducted. Before October 2015, incidental patients were treated similarly to symptomatic cases, undergoing biopsy or surgical excision upon diagnosis (early cohort). Post October 2015 (late cohort), treatment decisions were guided by PET/CT findings, with 18F-DOPA PET/CT confirming diagnosis and staging. For tumors with low 18F-FDG uptake, an expectant observation approach was considered. Patient characteristics, diagnostic methods, image findings at diagnosis, treatment courses, and responses were compared between cohorts. RESULTS: Thirty infants less than 18 months were identified with incidental neuroblastoma and completed PET/CT at diagnosis. The early and late cohorts each comprised 15 patients. In the late cohort, nine out of 15 patients (60%) presented with localized FDG non-avid tumors were offered the option of expectant observation. Of these, seven patients opted for observation, thereby avoiding surgery. Treatment outcomes were comparable between early and late cohorts, except for one mortality of a patient who, despite showing 18F-FDG activity, declined treatment. CONCLUSIONS: This study demonstrates the potential utility of 18F-DOPA and 18F-FDG PET/CT scans in aiding clinical decision-making for infants with localized, incidental neuroblastoma. Given the concerns regarding radiation exposure, such imaging may be valuable for cases with suspected metastasis, initial large tumor size, or growth during follow-up.
Subject(s)
Dihydroxyphenylalanine , Fluorodeoxyglucose F18 , Neuroblastoma , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Humans , Neuroblastoma/diagnostic imaging , Neuroblastoma/therapy , Neuroblastoma/pathology , Infant , Male , Female , Positron Emission Tomography Computed Tomography/methods , Retrospective Studies , Dihydroxyphenylalanine/analogs & derivatives , Infant, Newborn , Incidental Findings , Feasibility Studies , Follow-Up Studies , Clinical Decision-Making , PrognosisABSTRACT
OBJECTIVE: To evaluate the muscle thickness and walking test in people with haemophilia A (PWH) and their correlation to joint health and functional impairments. DESIGN: Cross-sectional study. RESULTS: 29 severe/moderate PWH were enrolled. Muscle thickness of quadriceps and medial gastrocnemius were measured using ultrasound. Joint health and functional capacity were assessed using Haemophilia Joint Health Score (HJHS), Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US), 6-Minute Walking test (6MWT), Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL), and Haemophilia Activities List (HAL). Quadriceps muscle thickness significantly correlated with HJHS knee, HEAD-US knee, and HAL. Calf muscle thickness significantly correlated with the HJHS ankle. After adjusted age and BMI, calf muscle thickness was inversely associated with the HJHS ankle. 6MWT was found to significantly correlate with HJHS total, HEAD-US total, Haem-A-QoL, and HAL. CONCLUSION: Muscle thickness and the distance of 6MWT were linked to assessment of joint health, quality of life and activity participation in PWH. Ultrasound measurement of muscle thickness and walking test appear to be useful tools for the assessment of joint health and functional status in PWH.
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Infant-type hemispheric glioma (IHG) is a rare pediatric brain tumor with variable response to chemotherapy and radiotherapy. Molecular insights into IHG can be useful in identifying potentially active targeted therapy. A male fetus was found to have congenital hydrocephalus at the gestational age of 37 weeks. Fetal MRI showed a 2.6 × 2.0-cm tumor located at the frontal horn of the left lateral ventricle, involving the left basal nuclei and thalamus. Tumor biopsy at the age of 2 days revealed an IHG consisting of spindle tumor cells with strong expression of GFAP and ALK. Targeted RNA sequencing detected a novel fusion gene of SOX5::ALK. After initial chemotherapy with cyclophosphamide, carboplatin, and etoposide for 2 cycles, the tumor size progressed markedly and the patient underwent a subtotal resection of brain tumor followed by treatment with lorlatinib, an ALK tyrosine kinase inhibitor with central nervous system (CNS) activity. After 3 months of treatment, reduction of tumor size was observed. After 14 months of treatment, partial response was achieved, and the infant had normal growth and development. In conclusion, we identified a case of congenital IHG with a novel SOX5::ALK fusion that had progressed after chemotherapy and showed partial response and clinical benefit after treatment with the CNS-active ALK inhibitor lorlatinib.
Subject(s)
Aminopyridines , Brain Neoplasms , Carcinoma, Non-Small-Cell Lung , Glioma , Lactams , Lung Neoplasms , Pyrazoles , Infant , Child , Male , Humans , Infant, Newborn , Lung Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Anaplastic Lymphoma Kinase/genetics , Lactams, Macrocyclic/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Brain Neoplasms/therapy , Brain Neoplasms/drug therapy , Glioma/therapy , Glioma/drug therapy , SOXD Transcription FactorsABSTRACT
Encapsulated cell therapy (ECT) shows significant potential for treating neurodegenerative disorders including Alzheimer's and Parkinson's, which currently lack curative medicines and must be managed symptomatically. This novel technique encapsulates functional cells with a semi-permeable membrane, providing protection while enabling critical nutrients and therapeutic substances to pass through. Traditional ECT procedures, on the other hand, pose difficulties in terms of cell survival and retrieval. We introduce the Microtube Array Membrane (MTAM), a revolutionary technology that solves these constraints, in this comprehensive overview. Microtube Array Membrane has distinct microstructures that improve encapsulated cells' long-term viability by combining the advantages of macro and micron scales. Importantly, the MTAM platform improves biosafety by allowing the entire encapsulated unit to be retrieved in the event of an adverse reaction. Our findings show that MTAM-based ECT has a great potential in a variety of illness situations. For cancer treatment, hybridoma cells secreting anti-CEACAM 6 antibodies inhibit triple-negative breast cancer cell lines for an extended period of time. In animal brain models of Alzheimer's disease, hybridoma cells secreting anti-pTau antibodies successfully reduce pTau buildup, accompanied by improvements in memory performance. In mouse models, MTAM-encapsulated primary cardiac mesenchymal stem cells dramatically improve overall survival and heart function. These findings illustrate the efficacy and adaptability of MTAM-based ECT in addressing major issues such as immunological isolation, cell viability, and patient safety. We provide new possibilities for the treatment of neurodegenerative illnesses and other conditions by combining the potential of ECT with MTAM. Continued research and development in this subject has a lot of promise for developing cell therapy and giving hope to people suffering from chronic diseases.
Subject(s)
Brain , Cell- and Tissue-Based Therapy , Animals , Mice , Humans , Biological Transport , Cell Line , Disease Models, AnimalABSTRACT
Neuroblastoma, a childhood cancer affecting the sympathetic nervous system, continues to challenge the development of potent treatments due to the limited availability of druggable targets for this aggressive illness. Recent investigations have uncovered that phosphoglycerate dehydrogenase (PHGDH), an essential enzyme for de novo serine synthesis, serves as a non-oncogene dependency in high-risk neuroblastoma. In this study, we show that homoharringtonine (HHT) acts as a PHGDH inhibitor, inducing intricate alterations in cellular metabolism, and thus providing an efficient treatment for neuroblastoma. We have experimentally verified the reliance of neuroblastoma on PHGDH and employed molecular docking, thermodynamic evaluations, and X-ray crystallography techniques to determine the bond interactions between HHT and PHGDH. Administering HHT to treat neuroblastoma resulted in effective cell elimination in vitro and tumor reduction in vivo. Metabolite and functional assessments additionally disclosed that HHT treatment suppressed de novo serine synthesis, initiating intricate metabolic reconfiguration and oxidative stress in neuroblastoma. Collectively, these discoveries highlight the potential of targeting PHGDH using HHT as a potent approach for managing high-risk neuroblastoma.
Subject(s)
Neuroblastoma , Phosphoglycerate Dehydrogenase , Humans , Child , Homoharringtonine , Molecular Docking Simulation , Enzyme Inhibitors , Neuroblastoma/drug therapy , SerineABSTRACT
Twelve Asian patients with sarcoma received interval-compressed (ic-) chemotherapy scheduled every 14 days with a regimen of vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1200-2200 mg/m2) (VDC) alternating with a regimen of ifosfamide (9000 mg/m2) and etoposide (500 mg/m2) (IE), with filgrastim (5-10 mcg/kg/day) between cycles. Carboplatin (800 mg/m2) was added for CIC-rearranged sarcoma. The patients were treated with 129 cycles of ic-VDC/IE with a median interval of 19 days (interquartile range [IQR], 15-24 days. Median nadirs (IQR) were neutrophil count, 134 (30-396) × 106/L at day 11 (10-12), recovery by day 15 (14-17) and platelet count, 35 (23-83) × 109/L at day 11 (10-13), recovery by day 17 (14-21). Fever and bacteremia were observed in 36% and 8% of cycles, respectively. The diagnoses were Ewing sarcoma (6), rhabdomyosarcoma (3), myoepithelial carcinoma (1), malignant peripheral nerve sheath tumor (1), and CIC-DUX4 Sarcoma (1). Seven of the nine patients with measurable tumors responded (one CR and six PR). Interval-compressed chemotherapy is feasible in the treatment of Asian children and young adults with sarcomas.
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BACKGROUND: Medical clowning for children has been found to be effective at enhancing parents' psychological well-being during preoperative preparation, but has not been found during cancer treatment. This study aimed to examine whether and how medical clowning influenced the emotions of parents of children undergoing cancer treatment. METHODS: In this quasi-experimental study, 96 parents of children receiving inpatient cancer treatment were recruited, from June 2018 through April 2020. A demographic questionnaire measuring characteristics of parent and dyadic child, Brief Symptom Rating Scale measuring psychological distress of the parent, and Mood Assessment Scale measuring emotional status of parent and child were administered 1 day before a clowning service. The day after the clowning service, the Mood Assessment Scale again collected emotional status for parent and child. Descriptive analysis, bivariate analysis, and structural equation modeling to fit the actor-partner, cross-lagged model were used. FINDINGS: Parents experienced a low degree of psychological distress that called for emotional management. The indirect effect of medical clowning on parents' emotions through children's emotions was significant, as were the direct effect and total effect of medical clowning on parents' emotions. DISCUSSION: Parents experienced psychological distress during their child's inpatient cancer treatment. Medical clowning can directly improve children's emotions and through this pathway indirectly improve their parents' emotions. APPLICATION TO PRACTICE: There is need to monitor psychological distress and provide interventions for parents of children undergoing cancer treatment. Medical clowns should continue to serve parent-child dyads in pediatric oncology practice and become members of multidisciplinary health care teams.
Subject(s)
Neoplasms , Parents , Humans , Parents/psychology , Emotions , Neoplasms/therapy , Neoplasms/psychology , Surveys and Questionnaires , Hospitalization , Parent-Child RelationsABSTRACT
BACKGROUND: Childhood cancer survivors are at a high risk of medical consequences of their disease and treatment. There is growing information about the long-term health issues of childhood cancer survivors; however, there are very few studies describing the health care utilization and costs for this unique population. Understanding their utilization of health care services and costs will provide the basis for developing strategies to better serve these individuals and potentially reduce the cost. OBJECTIVE: This study aims to determine the utilization of health services and costs for long-term survivors of childhood cancer in Taiwan. METHODS: This is a nationwide, population-based, retrospective case-control study. We analyzed the claims data of the National Health Insurance that covers 99% of the Taiwanese population of 25.68 million. A total of 33,105 children had survived for at least 5 years after the first appearance of a diagnostic code of cancer or a benign brain tumor before the age of 18 years from 2000 to 2010 with follow-up to 2015. An age- and gender-matched control group of 64,754 individuals with no cancer was randomly selected for comparison. Utilization was compared between the cancer and no cancer groups by χ2 test. The annual medical expense was compared by the Mann-Whitney U test and Kruskal-Wallis rank-sum test. RESULTS: At a median follow-up of 7 years, childhood cancer survivors utilized a significantly higher proportion of medical center, regional hospital, inpatient, and emergency services in contrast to no cancer individuals: 57.92% (19,174/33,105) versus 44.51% (28,825/64,754), 90.66% (30,014/33,105) versus 85.70% (55,493/64,754), 27.19% (9000/33,105) versus 20.31% (13,152/64,754), and 65.26% (21,604/33,105) versus 59.36% (38,441/64,754), respectively (all P<.001). The annual total expense (median, interquartile range) of childhood cancer survivors was significantly higher than that of the comparison group (US $285.56, US $161.78-US $535.80 per year vs US $203.90, US $118.98-US $347.55 per year; P<.001). Survivors with female gender, diagnosis before the age of 3 years, and diagnosis of brain cancer or a benign brain tumor had significantly higher annual outpatient expenses (all P<.001). Moreover, the analysis of outpatient medication costs showed that hormonal and neurological medications comprised the 2 largest costs in brain cancer and benign brain tumor survivors. CONCLUSIONS: Survivors of childhood cancer and a benign brain tumor had higher utilization of advanced health resources and higher costs of care. The design of the initial treatment plan minimizing long-term consequences, early intervention strategies, and survivorship programs have the potential to mitigate costs of late effects due to childhood cancer and its treatment.
Subject(s)
Brain Neoplasms , Leukemia , Child , Female , Humans , Adolescent , Child, Preschool , Follow-Up Studies , Case-Control Studies , Retrospective Studies , Brain Neoplasms/epidemiology , Brain Neoplasms/therapy , Patient Acceptance of Health Care , National Health ProgramsABSTRACT
The half life of recombinant factor VIII-Fc (rFVIII-Fc) for people with hemophilia A (PwHA) varies greatly. Understanding the factors influencing the variation and assessment of rFVIII-Fc half life is important for personalized treatment. Eighty-five severe-type PwHA with rFVIII-Fc treatment receiving an evaluation of half life by the Web-Accessible Population Pharmacokinetic (PK) Service-Hemophilia during 2019-2021 were retrospectively enrolled. The 50-patient PK profiles before 2021 were used for analysis and developing prediction models of half life, and the 35-patient PK profiles in 2021 were used for external validation. The patients in the development cohort were aged 8-64, with a median rFVIII-Fc half life of 20.75 h (range, 8.25-41.5 h). By multivariate linear regression analysis, we found two, four, and five predictors of rFVIII-Fc half life for the blood groups non-O, O patients, and overall patients, respectively, including baseline VWF:Ag, BMI, VWF:activity/VWF:Ag ratio, body weight, O blood group, inhibitor history, HCV infection, and hematocrit. The three prediction equations of rFVIII-Fc half life (T) were respectively developed as T for non-O group patients = -0.81 + 0.63 × (BMI, kg/m2) + 6.07 × (baseline VWF:Ag, IU/mL), T for O group patients = -0.68 + 13.30 × (baseline VWF:Ag, IU/mL) + 0.27 × (BW, kg) - 1.17 × (BMI, kg/m2) + 16.02 × (VWF:activity/VWF:Ag ratio), and T for overall patients = -1.76 + 7.24 × (baseline VWF:Ag, IU/mL) - 3.84 × (Inhibitor history) + 2.99 × (HCV infection) - 2.83 × (O blood group) + 0.30 × (Hct, %), which explained 51.97%, 75.17%, and 66.38% of the half life variability, respectively. For external validation, there was a significant correlation between the predicted and observed half lives in the validation cohort. The median half life deviation was +1.53 h, +1.28 h, and +1.79 h for the equations of non-O group, O group, and overall group patients, respectively. In total, eight predictors influencing rFVIII-Fc half life were identified. Prediction equations of rFVIII-Fc half life were developed for the non-O and O blood groups and overall PwHA with a good degree of external validation. The equations could be applied to patients aged 8-64 without the need for PK blood sampling and clinically valuable for personalized therapy.
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BACKGROUND: The International Classification of Functioning, Disability and Health (ICF) core set (CS) facilitates the standardization of functioning and impairment assessment for integration of holistic care. OBJECTIVE: This study developed an ICF CS for interviewing pediatric brain tumor survivors in Taiwan to help healthcare professionals in implementing disability assessment and management measures. METHODS: A group of 29 experts in 10 relevant fields with at least 5 years of experience working with children with brain tumors participated in this study. The first questionnaire contained 247 second-level ICF categories. The experts rated the significance of each category by using a 5-point Likert scale. Correlations between individual and group scores were calculated to determine consensus. Categories with an average rating of higher than 4 and for which greater than or equal to 80% (23) of the participants provided a rating of 4 or higher were included in the final CS. RESULTS: The final CS contained a total of 57 ICF categories: 20 from the Body Functions and Structures component, 36 from the Activities and Participation component, and 1 from the Environmental Factors component. CONCLUSION: The ICF CS for pediatric brain tumor survivors provides a framework for relevant healthcare professionals to deliver patient-centered care, ensuring that services focus on all areas of development. IMPLICATIONS FOR PRACTICE: Patient ratings for this ICF CS may serve as a new practical and effective patient-reported information tool for acquiring patient input and for the systematic monitoring of pediatric brain tumor survivors in clinical practice. Further research should be conducted on this CS to verify our findings.
Subject(s)
Brain Neoplasms , International Classification of Functioning, Disability and Health , Child , Humans , East Asian People , Activities of Daily Living , Disability Evaluation , Survivors , Brain Neoplasms/therapyABSTRACT
BACKGROUND: Recombinant factor VIII-Fc (rFVIIIFc) became available in Taiwan in 2018. Before this date, no people with hemophilia A (PwHA) were enrolled in a clinical trial of rFVIIIFc. We investigated changes in bleeding outcomes and product utilization in PwHA switching from rFVIII to rFVIIIFc. METHODS: Data were collected for Taiwanese PwHA (severe-type) who switched from rFVIII to rFVIIIFc, including annualized bleeding rate (ABR) and weekly dose consumption 12 months pre-switch and > 6 months post-switch. RESULTS: The 51 patients were divided into 3 groups according to their pre-switch treatment: on-demand treatment, intermittent periodic prophylaxis, and regular prophylaxis. In every group, the post-switch median ABR was significantly reduced, with no significant differences between groups. Meanwhile, the post-switch median weekly dose of each group was significantly increased. In 32 patients on pre-switch prophylaxis, switching brought a further reduction in median ABR, associated with a significant increase in median weekly dose. No adverse effects or novel inhibitor development were seen. CONCLUSION: This is the first report from Asia on real-world experience of rFVIIIFc, showing that switching to rFVIIIFc prophylaxis led to further reduction in ABR and increase in weekly dose for all patient groups, even those on pre-switch rFVIII prophylaxis.
Subject(s)
Hemophilia A , Humans , Hemophilia A/complications , Hemophilia A/drug therapy , Half-Life , Recombinant Fusion Proteins/pharmacology , Treatment Outcome , Immunoglobulin Fc Fragments/adverse effects , Hemorrhage/prevention & control , Hemorrhage/chemically induced , Factor VIII/adverse effectsABSTRACT
BACKGROUND: This study analyzed data from two consecutive protocols for children newly diagnosed with acute lymphoblastic leukemia (ALL) to determine the clinical impact of minimal/measurable residual disease (MRD) and recently identified tumor genetic subtypes. METHODS: Genetic subtypes were determined by sequential approaches including DNA indexing, reverse transcriptase-polymerase chain reaction, multiplex ligation-dependent probe amplification, and RNA-sequencing. MRD was assessed by flow cytometry. The Taiwan Pediatric Oncology Group TPOG-ALL-2013 study enrolled patients who received MRD-directed therapy. RESULTS: The 5-year event-free survival (EFS) and overall survival rates in the 2013 cohort were 77.8% and 86.9% compared to those of the 2002 cohort, which were 62.4% and 76.5%. Among patients treated with MRD-guided therapy, those with ETV6-RUNX1 fusion and high hyperdiploidy had the highest 5-year EFS (91.4% and 89.6%, respectively). The addition of dasatinib improved outcomes in patients with BCR-ABL1 ALL. Recently identified subtypes like DUX4-rearranged, ZNF384-rearranged, MEF2D-rearranged, and PAX5alt subtypes were frequently positive for MRD after remission induction, and these patients consequently received intensified chemotherapy. Treatment intensification according to the MRD improved the outcomes of patients presenting DUX4 rearrangements. In high-risk or very-high-risk subtypes, the TPOG-ALL-2013 regimen did not confer significant improvements compared to TPOG-ALL-2002, and the outcomes of BCR-ABL1-like, MEF2D-rearranged, and KMT2A-rearranged ALL subtypes (in addition to those of T-cell ALL) were not sufficiently good. Novel agents or approaches are needed to improve the outcomes for these patients. CONCLUSIONS: The TPOG-ALL-2013 study yielded outcomes superior to those of patients treated in the preceding TPOG-ALL-2002 study. This study provides important data to inform the design of future clinical trials in Taiwan. PLAIN LANGUAGE SUMMARY: MRD-directed therapy improved the outcomes for pediatric ALL, especially standard-risk patients. Genomic analyses and MRD might be used together for risk-directed therapy of childhood ALL. Our work provides important data to inform the design of future clinical trials in Taiwan.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Neoplasm, Residual/genetics , Neoplasm, Residual/diagnosis , Prognosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Dasatinib/therapeutic use , Remission InductionABSTRACT
There is an increasing number of reported cases with neurological manifestations of COVID-19 in children. Symptoms include headache, general malaise, ageusia, seizure and alterations in consciousness. The differential diagnosis includes several potentially lethal conditions including encephalopathy, encephalitis, intracranial hemorrhage, thrombosis and adrenal crisis. We report the case of a 17-year-old boy with a positive antigen test of COVID-19 who presented with fever for one day, altered mental status and seizure, subsequently diagnosed with adrenal insufficiency. He had a history of panhypopituitarism secondary to a suprasellar craniopharyngioma treated with surgical resection; he was treated with regular hormone replacement therapy. After prompt administration of intravenous hydrocortisone, his mental status returned to normal within four hours. He recovered without neurologic complications. Adrenal insufficiency can present with neurological manifestations mimicking COVID-19 encephalopathy. Prompt recognition and treatment of adrenal insufficiency, especially in patients with brain tumors, Addison's disease or those recently treated with corticosteroids, can rapidly improve the clinical condition and prevent long-term consequences.