Theodotis Papageorgiou

Metabolic syndrome in children and adolescents with acute lymphoblastic leukemia after the completion of chemotherapy.

The metabolic syndrome is a cluster of potent risk factors for cardiovascular diseases. To provide information on the late complications of chemotherapy for acute lymphoblastic leukemia (ALL), the authors prospectively studied the frequency of overweight, obesity, and metabolic syndrome in survivors of ALL in the initial years after the completion of therapy. Children and adolescents were classified as having the metabolic syndrome if they met three or more of the following criteria: hypertriglyceridemia, low levels of high-density lipoprotein (HDL), high fasting glucose, obesity, and hypertension. Obesity was defined on the basis of Body Mass Index (BMI) (kg/m2) standard deviation scores or z-scores. Cutoff points for triglycerides and HDL were taken from equivalent pediatric percentiles with the cutoff points proposed by the Adult Treatment Panel III (ATPIII). Hyperglycemia was defined using the ATPIII cutoff points. Elevated systolic or diastolic blood pressure was defined as a value greater than the 95th percentile for age, gender, and height. Fifty-two subjects (29 male and 23 female) with a median age of 15.2 years (range 6.1-22.6 years) were evaluated. Median interval since completion of therapy was 37 months (range 13-121 months). All of them had been treated according to the ALL-BFM 90 chemotherapy protocol and none had received cranial radiotherapy. Of the 52 subjects, 25 (48%) were overweight (BMI z-score >1.5) and 3 (5.76%) were obese (BMI z-score >2); among them, 1 was severely obese (BMI z-score >2.5). Three criteria for the metabolic syndrome (high triglyceride levels, glucose intolerance, and obesity) were fulfilled by three subjects (5.76%). Twenty-nine subjects (55.7%) had at least one risk factor for metabolic syndrome. Hyperglycemia and hypertension were infrequent. Prompt recognition of the risk factors for metabolic syndrome and intervention seem mandatory to ensure early prevention of cardiovascular disease in survivors of ALL.

Expression of Multidrug Resistance 1 (MDR1), Multidrug Resistance-Related Protein 1 (MRP1), Lung Resistance Protein (LRP), and Breast Cancer Resistance Protein (BCRP) Genes and Clinical Outcome in Childhood Acute Lymphoblastic Leukemia

The aim of this prospective study was to analyze the expression of messenger RNA of genes, such as MDR1, MRP1, BCRP, and LRP, implicated in the mechanism of multidrug resistance (MDR) in relation to the response to induction chemotherapy and relapse and these genes’ correlation with each other and with pretreatment laboratory and clinical characteristics. We prospectively studied 49 children (26 boys and 23 girls) with acute lymphoblastic leukemia (ALL) (median age, 5.5 years; range, 15 months to 12.5 years) who were treated with the BFM95 chemotherapy protocol. We used bone marrow mononuclear cells from 7 healthy children as controls. The expression of MDR genes and the β-actin housekeeping gene was detected by the reverse transcription-polymerase chain reaction with the appropriate primers. The mean expression of each MDR gene was significantly higher in the patients than in the control group (P <.01). We found statistically significant correlations between MRP1 and LRP expression and between MRP1 or LRP expression and MDR1 expression (P <.05). High expression for the MDR1 gene was found in 18 patients (36.7%), and their prognoses were significantly worse than those with low expression (event-free survival, 55.56% versus 86.67%;P =.03, log-rank test). Expression of each of the MDR genes was independent of the initial white blood cell count, immunophenotype, National Cancer Institute risk classification, and prednisone response. Interestingly, MDR1 expression was significantly higher at relapse than at diagnosis for 4 sample pairs. Evaluation of MDR1 expression at diagnosis of childhood ALL may contribute to the early identification of patients at risk of treatment failure.

SPINAL EPIDURAL EXTRASKELETAL EWING SARCOMA IN AN ADOLESCENT BOY: A Case Report

Extraskeletal Ewing sarcoma (EES) represents a rare soft tissue malignant neoplasm histologically similar to skeletal Ewing sarcoma. It occurs mainly in adolescents and young adults and commonly affects the paravertebral regions. The differential diagnosis includes other small, blue round cells tumors. The authors report a case of an EES involving the spinal epidural and paravertebral spaces in an adolescent boy. EES diagnosis was confirmed by features of histologic analysis and immunohistochemistry and by the presence of the t(11;22)(q24;q12) chromosomal translocation by reverse transcriptase–polymerase chain reaction.

Severe hyperlipidemia in a child with acute lymphoblastic leukemia treated with L‐asparaginase and prednisone

The current cure rate for children with acute lymphoblastic leukemia (ALL) in developed countries is about 80%. 1 A very important advancement in treatment responsible for this accomplishment was the combination of multiple agents in chemotherepy which was introduced in 1960. Current investigations are focused on the development of more efficient and less toxic treatment regimens. Asparaginase has been an effective drug in the treatment of childhood ALL for more than 30 years, and has become an important component of most childhood ALL regimens during the remission induction or intensification phases of treatment. Asparaginase is a bacteria-derived enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid and depletes the blood of this amino acid. In most tissues, asparagine is synthesized from aspartic acid and glutamine by the enzyme asparagine synthase and can respond to asparagine depletion by up-regulation of this enzyme. In contrast, sensitive lymphoid malignancies do not up-regulate asparagine synthase and, therefore, depend on exogenous circulating asparagine for protein synthesis. 2

Mannose binding lectin and ficolin-2 polymorphisms are associated with increased risk for bacterial infections in children with B acute lymphoblastic leukemia.

We aimed to investigate whether the presence of mannose binding lectin (MBL2), ficolin 2 (FCN2) polymorphisms or the combined deficiency significantly influence the risk and subsequently the frequency of chemotherapy‐induced bacterial infections in children with B acute lymphoblastic leukemia (B‐ALL).

Invasive fungal infections in children with hematological malignancies: a 5-year study.

Invasive fungal infections (IFI) are life-threatening infections and represent an important cause of morbidity and mortality in immunocompromised children, particularly those with hematological malignancies and stem cell transplantation [1]. Although in the last decades there has been an improvement in event-free survival (EFS) in children with cancer secondary to advances in current treatment and successful management of bacterial and viral infections, IFI remain a devastating problem [2, 3]. Many factors contribute to developing of fungal infections. More than 90% of patients who develop an IFI have at least one of the following factors: cytotoxic chemotherapy, corticosteroid therapy, mucositis, bone marrow transplantation, long-term parenteral nutrition, and prolonged and/or severe neutropenia [4, 5]. The purpose of this study, therefore, was to evaluate the frequency of IFI in a major pediatric oncology center in Greece and to report our results regarding patient characteristics, diagnosis, efficacy of treatment, and outcome of IFI. A retrospective analysis for documented or suspected fungal infection was performed in the Pediatric Oncology Unit of the 2nd Pediatric Department

Lumbar puncture complicated by spinal epidural hematoma in a child with leukemia

We report a case of spinal epidural hematoma (SEH) preceded by diagnostic lumbar puncture (LP) in a 5‐year‐old boy with acute lymphoblastic leukemia. MRI confirmed the presence of SEH between T7 and L5 levels, but the patient showed fast recovery during the next hours and conservative management was elected.

Epileptic seizures after octreotide administration in a 6.5-year-old female with ALL and L-asparaginase associated pancreatitis: a possible drug interaction.

INTRODUCTION Octreotide is a synthetic somatostatin analogue which has been suggested for use in the management of acute pancreatitis, though its safety and effectiveness in the pediatric setting has not been extensively studied. CASE REPORT we present a rare case of a 6.5-year-old female with acute lymphoblastic leukemia (ALL) and L-asparaginase (L-asp) induced pancreatitis, who developed epileptic seizures, possibly associated with octreotide administration. Her imaging and laboratory findings ruled out a leukemic involvement or infection of CNS. The EEG revealed repetitive sharp waves maximal on the frontal and temporal areas of the right hemisphere. The child was treated with diazepam and she continued with systemic anticonvulsant treatment with levetiracetam. After 2 weeks of conservative treatment, pancreatitis resolved and she continued her chemotherapy protocol. Levetiracetam treatment lasted 8 months. 7 months after the first episode, EEG was reported as normal, and the child completed the chemotherapy protocol without any further severe complications. CONCLUSIONS Larger and well designed studies are needed to warrant the safety of octreotide in pediatric population.

Transient myeloproliferative disorder in a newborn with down syndrome treated with rasburicase for the risk of development of tumor lysis syndrome: A case report

IntroductionTransient myeloproliferative disorder is a hematologic abnormality characterized by an uncontrolled proliferation of myeloblasts in peripheral blood and bone marrow that primarily affects newborns and babies with Down syndrome. Tumor lysis syndrome is rarely associated with transient myeloproliferative disorder.Case presentationTransient myeloproliferative disorder was diagnosed in a seven-day-old baby girl with Down syndrome, who was referred to our department due to hyperleukocytosis. Our patient developed tumor lysis syndrome, successfully treated with rasburicase, as a complication of transient myeloproliferative disorder resulting from rapid degradation of myeloid blasts after initiation of effective chemotherapy.ConclusionsTumor lysis syndrome is rarely reported as a complication of transient myeloproliferative disorder. To the best of our knowledge, this is the first case of a newborn with Down syndrome and transient myeloproliferative disorder treated with rasburicase for developing tumor lysis syndrome.

Septic pulmonary embolism due to Staphylococcus aureus

© 2008 Japan Pediatric Society We read with great interest the report from Yuksel et al. regarding the development of septic pulmonary embolism secondary to osteomyelitis published in Pediatrics International . 1 Septic pulmonary embolism (SPE) represents an uncommon disorder that typically presents with an insidious onset of fever, respiratory symptoms, and pulmonary infi ltrates. 2 Generally the diagnosis of SPE is suggested on radiography and clinical evidence of infection. 3,4 We report the case of a 9-year-old boy who developed SPE due to Staphylococcus aureus without any predisposing risk factors. A 9-year-old boy was admitted to Second Department of Pediatrics , Aristotle University of Thessaloniki with fever and marked respiratory distress. His illness had begun 2 days previously with cough and fever. On physical examination the patient was found to be pyrexial, tachycardiac and tachypneic with low oxygen saturation on room air (SaO 2 : 90%) and stable blood pressure. Chest examination indicated diminished breath sounds on both sides. Laboratory data indicated leukocytosis (white blood cell count, 19000/mm 3 with 97% neutrophils), erythrocyte sedimentation rate 70 mm/h, C-reactive protein 29.92 mg/dL and procalcitonin 20.02 ng/mL. Arterial blood gas indicated marked hypoxemia with a PO 2 of 59 mmHg. Chest radiography indicated bilateral lower lobe infi ltrates. Empiric broad-spectrum i.v. antibiotics (amoxicillin + clavulanic acid and clarythromycin) were initiated immediately. Because of the progressive dyspnea chest computed tomography (CT) was performed on day 2 after admission, which showed multiple scattered nodular lesions, most located subpleurally and measuring approximately 1 – 3 cm in diameter, in both lung fi elds, suggestive of septic emboli ( Fig. 1 ). On day 3 the patient’s clinical condition had improved and blood cultures had grown methicillin-resistant S. aureus (MRSA). Therefore, a diagnosis of SPE secondary to S. aureus septicemia was established. The patient was treated with i.v. vancomycin. On the 6th day of hospitalization he became afebrile but had a severe left-side chest pain worsened by movement and deep breaths. Lung auscultation indicated diminished murmur over the left lung fi elds. Immediate bedside chest radiograph and CT indicated pneumothorax on the left lung. The boy was taken to the operating room for surgical drainage and thoracostomy to manage the pneumothorax. These treatments resulted in a successful outcome, and the boy was discharged on day 22 in excellent clinical condition. Septic pulmonary embolism is defi ned as the coexistence of multiple lung infi ltrates coupled with isolation of bacteria from the blood or their infection source. SPE is a often a complication Letter to the Editor Septic pulmonary embolism due to Staphylococcus aureus