Maria Scalzone

Platinum compounds in children with cancer: toxicity and clinical management

Platinum compounds are widely used in the treatment of pediatric tumors such as neuroblastoma, germ-cell tumors, osteosarcoma, retinoblastoma, hepatoblastoma, brain tumors (low-grade gliomas and medulloblastoma/PNET), and relapsed and refractory lymphomas. The three major platinum compounds (cisplatin, carboplatin, and oxaliplatin) have a similar pharmacokinetics profile and mechanism of action, but the differences in their chemical structure are responsible for their different antitumor activity and toxicity. In this review, we have described the main characteristics of cisplatin, carboplatin, and oxaliplatin, focusing on their toxic effects and possible strategies to prevent them to improve the clinical outcomes in pediatric cancer patients. The underlying mechanism of each platinum-related toxicity is shown together with the clinical manifestations. Furthermore, possible preventive strategies are suggested to reduce the negative impact of platinum compounds on the quality of life of children with cancer. Cisplatin seems to be mostly ototoxic and nephrotoxic, carboplatin mainly produces myelosuppression, whereas oxaliplatin induces predominantly peripheral sensory neurotoxicity. In contrast, nausea and vomiting can be linked to all platinum compounds, although cisplatin exerts the strongest emetic effect. A correct knowledge of pharmacokinetics and toxicological profile of platinum compounds may aid physicians prevent their toxicity on auditory, nervous, renal, and bone marrow function, improving the quality of life of pediatric cancer patients.

Hepatic veno-occlusive disease: A chemotherapy-related toxicity in children with malignancies

Hepatic veno-occlusive disease (VOD) is a major manifestation of liver toxicity associated with conventional and high-dose chemotherapy in children affected by hematologic malignancies and certain solid tumors. Clinically, patients present with jaundice, painful hepatomegaly, and fluid retention, which may evolve into multi-organ failure, a hallmark of severe disease. The pathogenesis is complex and not completely understood, but the damage to sinusoidal endothelium, typically caused by toxic metabolites released from antineoplastic drugs, is thought to play a crucial role, together with cytokine activation, immune deregulation, and coagulopathy.Diagnosis is based on clinical criteria supported by characteristic ultrasound findings, with the gold standard investigation being hepatic-venous pressure gradient measurement and biopsy. Several treatment options have been tested; the most convincing approach to date is the use of defibrotide, a novel oligonucleotide with antithrombotic and antiplatelet aggregating properties, as well as endothelial-stabilizing effects. This agent, together with other specific forms of supportive care, has shown efficacy in the treatment of established VOD and promising results in the prevention of VOD in pediatric patients receiving chemotherapy.

Temozolomide in the treatment of newly diagnosed diffuse brainstem glioma in children: a broken promise?

Abstract Background: The purpose of this study was to assess the efficacy and toxicity of radiotherapy (RT) with concurrent temozolomide (TMZ) chemotherapy followed by adjuvant TMZ in children with diffuse intrinsic pontine glioma (DIPG). Methods: Patients younger than 18 years with newly diagnosed DIPG were enrolled. Children were treated with focal RT along with concurrent daily TMZ. Four weeks after completing the initial RT–TMZ schedule, adjuvant TMZ was given every 28 days up to 12 cycles or progression disease. Results: Fifteen children with a median age of 9 years were enrolled. Fourteenth out of the 15 patients completed the chemoradiotherapy. The toxicity associated with TMZ was primarily haematopoietic. At a median follow-up of 15 months 13 children had died and 2 children were alive with progressive disease. No patient experienced complete response (CR). The median time to progression was 7·15 months. Conclusion: Chemoradiotherapy with TMZ followed by adjuvant TMZ did not improve the poor prognosis associated with DIPG in children.

Treatment of pharyngeal non-Hodgkin lymphoma in a patient with Wiskott-Aldrich syndrome

Wiskott‐Aldrich syndrome (WAS) is characterized by primary immunodeficiency, thrombocytopenia and eczema. Patients with WAS have an increased risk to develop tumors. Non‐Hodgkin lymphoma (NHL) represents the most common malignancy occurring in WAS‐affected patients, diffuse‐large‐B‐cell lymphoma is the most frequently encountered variant. We describe a case of a patient with WAS and NHL in the pharynx, an atypical tumor site presentation. The patient was successfully treated with a reduced dose chemotherapy regimen plus anti‐CD20 monoclonal antibody. He is in complete remission 3 years from the start of treatment. Pediatr Blood Cancer 2012;59:318–319.

Errors Involving Patients Receiving Intrathecal Chemotherapy

Abstract Errors involving patients receiving intrathecal chemotherapy are a significant problem in oncology. Despite the improvement in the management of antineoplastic agents, unintentional intrathecal administration of chemotherapic drugs that are indicated only for systemic administration or intrathecal overdose of drugs regularly used for intrathecal chemotherapy, continue to occur. These events can result in severe neurotoxicity, usually fatal in outcome. We review reported cases of medication errors in intrathecal administration of chemotherapy described in the literature. Diverse rescue therapies have been proposed but the most effective means of managing these errors remains prevention.

Treatment of childhood sarcoma with irinotecan: bilirubin level as a predictor of gastrointestinal toxicity.

Abstract Irinotecan is a promising anticancer agent for the treatment of childhood cancer un-responsive to conventional chemotherapy. Its active metabolite, 7-ethyl-10 hydroxy-camptothecin (SN-38) is glucuronidated by a uridine-diphosphoglucuronosyl-transferase (UGT1A1) to form an inactive metabolite. It was supposed that patientswith the UGT1A1*28 polymorphism would have a greater prevalence of elevated pre-treatment serum bilirubin levels and higher toxicity. The aim of our study was to investigate the predictive value of pre-treatment bilirubin levels in the development of severe diarrhea in solid tumor patients treated with irinotecan. The survey included14 pediatric patients with refractory sarcomas treated with irinotecan (CPT-11). Patients were grouped based on the development of mild (G0-2) or severe (G3) gastrointestinal toxicity. The simple linear regression model and the non-parametric paired wilcoxon test were adopted for the analysis. P <0.05 was judged to indicate a significant difference. The results showed a significant increase in severity of diarrhea with in creasing total pre-treatment bilirubin. Therefore, we propose that pre-treatmentbilirubin levels can predict gastrointestinal toxicity in pediatric cancer.

Management of children with Thrombocytopenia‐absent radius syndrome: An institutional experience

Aim:  Thrombocytopenia‐absent radius (TAR) syndrome is characterised by bilateral absence of the radii in the presence of both thumbs and hypomegakaryocytic thrombocytopenia.

Hemophagocytic lymphohistiocytosis and visceral leishmaniasis in children: case report and systematic review of literature

Hemophagocytic lymphohistiocytosis is a potentially fatal disorder resulting from excessive activation and non-malignant proliferation of T lymphocytes and macrophages. Neoplasms, autoimmune disorders and systemic infections can cause secondary hemophagocytic syndrome. The association of hemophagocytic syndrome and visceral leishmaniasis is rarely found in childhood. We report a case of an infant affected by hemophagocytic lymphohistiocytosis secondary to visceral leishamniasis and describe all cases of hemophagocytic syndrome associated with visceral leishamniasis in childhood reported in literature, focusing on clinical manifestation, diagnosis and treatment.

Platinum compounds and sodium metabolism in children with diencephalic glioma

In this brief report we have described eight children affected by optic pathway/hypothalamus gliomas and treated with carboplatin and/or cisplatin, which developed a derangement of sodium and water metabolism, due to diabetes insipidus (DI) or to syndrome of inappropriate antidiuretic hormone secretion (SIADH) after surgical resection. In four out of these eight patients the treatment with platinum compounds produced prolonged haematological toxicity and in five out of them it caused neurosensorial bilateral hypoacusia. In addition cisplatin worsened electrolytes disturbances. Hence children with DI or SIADH should be carefully monitored before, during and after the treatment with platinum compounds.

Pott’s puffy tumour by Streptoccocus intermedius a rare complication of sinusitis

An 8-year-old child presented with persistent fever, headache and a frontal swelling. The medical history was significant for recurrent episodes of upper respiratory tract infections and frontal headache. On physical examination, she showed a good performance condition and normal neurologic status. On palpation, a tender, fluctuating, doughy and warm mass (9×7 cm) in the forehead …