ABSTRACT
Acute lymphoblastic leukemia (ALL) is the most prevalent cancer in children, and despite considerable progress in treatment outcomes, relapses still pose significant risks of mortality and long-term complications. To address this challenge, we employed a supervised machine learning technique, specifically random survival forests, to predict the risk of relapse and mortality using array-based DNA methylation data from a cohort of 763 pediatric ALL patients treated in Nordic countries. The relapse risk predictor (RRP) was constructed based on 16 CpG sites, demonstrating c-indexes of 0.667 and 0.677 in the training and test sets, respectively. The mortality risk predictor (MRP), comprising 53 CpG sites, exhibited c-indexes of 0.751 and 0.754 in the training and test sets, respectively. To validate the prognostic value of the predictors, we further analyzed two independent cohorts of Canadian (n = 42) and Nordic (n = 384) ALL patients. The external validation confirmed our findings, with the RRP achieving a c-index of 0.667 in the Canadian cohort, and the RRP and MRP achieving c-indexes of 0.529 and 0.621, respectively, in an independent Nordic cohort. The precision of the RRP and MRP models improved when incorporating traditional risk group data, underscoring the potential for synergistic integration of clinical prognostic factors. The MRP model also enabled the definition of a risk group with high rates of relapse and mortality. Our results demonstrate the potential of DNA methylation as a prognostic factor and a tool to refine risk stratification in pediatric ALL. This may lead to personalized treatment strategies based on epigenetic profiling.
Subject(s)
DNA Methylation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Canada , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Treatment Outcome , Prognosis , RecurrenceSubject(s)
Humans , Male , Infant , Gray Platelet Syndrome , Thrombocytopenia , Hemorrhagic Disorders , HypertrophySubject(s)
Gray Platelet Syndrome , Humans , Gray Platelet Syndrome/diagnosis , Gray Platelet Syndrome/genetics , Rare Diseases , Male , InfantSubject(s)
Betacoronavirus , Coronavirus Infections , Neoplasms , Pandemics , Pneumonia, Viral , Adolescent , COVID-19 , Child , Humans , Pneumonia, Viral/epidemiology , SARS-CoV-2ABSTRACT
La hipercalcemia asociada a procesos tumorales es un hallazgo poco frecuente en la edad pediátrica. El manejo terapéutico va encaminado a favorecer la calciuresis con diversos métodos farmacológicos e, incluso, técnicas de depuración extrarrenal. El objetivo de la exposición de este caso clínico es presentar a un paciente con hipercalcemia grave refractaria, que solo respondió a un tratamiento etiológico precoz con el empleo de quimioterapia, y se evitaron así las posibles complicaciones secundarias a dicha alteración electrolítica.
Hypercalcemia as a paraneoplastic syndrome is rare in children. Therapeutic management is aimed at promoting calciuresis with various pharmacological methods, even with extrarenal purification techniques. The aim of presenting this case is to highlight the importance of early etiologic treatment through chemotherapy as an urgent treatment in a refractory and severe hypercalcemia case, in order to avoid possible secondary complications due to this electrolyte disturbance.
Subject(s)
Humans , Male , Child , Paraneoplastic Syndromes/etiology , Lymphoma, Large B-Cell, Diffuse/complications , Emergencies , Hypercalcemia/etiologyABSTRACT
La hipercalcemia asociada a procesos tumorales es un hallazgo poco frecuente en la edad pediátrica. El manejo terapéutico va encaminado a favorecer la calciuresis con diversos métodos farmacológicos e, incluso, técnicas de depuración extrarrenal. El objetivo de la exposición de este caso clínico es presentar a un paciente con hipercalcemia grave refractaria, que solo respondió a un tratamiento etiológico precoz con el empleo de quimioterapia, y se evitaron así las posibles complicaciones secundarias a dicha alteración electrolítica.(AU)
Hypercalcemia as a paraneoplastic syndrome is rare in children. Therapeutic management is aimed at promoting calciuresis with various pharmacological methods, even with extrarenal purification techniques. The aim of presenting this case is to highlight the importance of early etiologic treatment through chemotherapy as an urgent treatment in a refractory and severe hypercalcemia case, in order to avoid possible secondary complications due to this electrolyte disturbance.(AU)
ABSTRACT
Hypercalcemia as a paraneoplastic syndrome is rare in children. Therapeutic management is aimed at promoting calciuresis with various pharmacological methods, even with extrarenal purification techniques. The aim of presenting this case is to highlight the importance of early etiologic treatment through chemotherapy as an urgent treatment in a refractory and severe hypercalcemia case, in order to avoid possible secondary complications due to this electrolyte disturbance.
Subject(s)
Hypercalcemia/etiology , Lymphoma, Large B-Cell, Diffuse/complications , Paraneoplastic Syndromes/etiology , Child , Emergencies , Humans , MaleSubject(s)
Abdominal Pain/etiology , Lymphoma, B-Cell/complications , Pancreatic Neoplasms/complications , Abdominal Pain/drug therapy , Abdominal Pain/pathology , Adolescent , Antineoplastic Agents , Humans , Immunohistochemistry , Immunophenotyping , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/pathology , Male , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathologyABSTRACT
OBJECTIVE: To report the effects of terlipressin treatment in four paediatric patients with catecholamine-resistant hypotensive septic shock. DESIGN AND SETTING: Case report in the pediatric intensive care unit of a university hospital. PATIENTS: Four children with severe septic shock and hypotension resistant to high doses of norepinephrine and other cathecolamines. INTERVENTIONS: Terlipressin was added to the standard treatment, by intravenous bolus at a dose of 0.02 mg/kg every 4 h during a maximum time of 3 days. MEASUREMENT AND RESULTS: In all cases, terlipressin induced a rapid and sustained improvement in mean arterial pressure, which allowed the lessening or even withdrawal of norepinephrine infusion. No related adverse effects were detected. CONCLUSION: Terlipressin might be considered, at least as a rescue therapy, for hypotension resistant to catecholamines in children with septic shock. Further studies are needed to confirm the beneficial effects found in our patients. The optimal administration schedule remains to be elucidated.
