Implementation of immunotherapy into the treatment of neuroblastoma - single center experience with the administration of dinutuximab and management of its adverse effects.

BACKGROUND: Neuroblastoma is the most common extracranial solid tumour of childhood with extremely heterogeneous bio-logical and clinical behaviour. Despite advances in its treatment, the long-term prognosis of patients with a high-risk and relapsed neuroblastoma remains poor. The implementation of immunotherapy into the treatment protocols has the potential to improve it. Dinutuximab, a chimeric monoclonal antibody, leads to the apoptosis of tumour cells through binding to the GD2 receptor. The article aim is to present the first experience of our centre with dinutuximab treatment. PATIENTS AND METHODS: In 2018-2019, we administered 31 cycles of dinutuximab to seven patients. Five patients with high-risk neuroblastoma received dinutuximab in the first line, in two patients with relapse, dinutuximab was administered in the second line of treatment. To evaluate the toxicity of the treatment, the nursing records of patients during immunotherapy were retrospectively analysed. RESULTS: Two patients treated with dinutuximab in the first line are in complete remission, three patients achieved a partial response. Both patients with relapsed neuroblastoma were dia-gnosed with a second relapse after immunotherapy and died of disease progression. The treatment tolerance was acceptable in most patients - in six patients adverse events were managed with adequate supportive care. These were mainly symptoms of capillary leak syndrome, pain and hypersensitivity reactions. In one patient, the treatment was discontinued due to severe neurotoxicity. CONCLUSION: Dinutuximab has a proven benefit in the eradication of the minimal residual disease in the treatment of neuroblastoma. Immunotherapy is currently the standard for first-line treatment of high-risk neuroblastoma. Its role in the treatment of relapsed neuroblastoma is a subject of several ongoing studies as well as the optimization of therapeutic regimens. Dinutuximab administration is associated with a considerable risk of severe adverse reactions, so the treatment belongs to the hands of an experienced paediatric oncology centre.

Treatment of rhabdomyosarcoma in children and adolescent from four low health expenditures average rates countries.

Background Survival of children with cancer in Eastern and Central Europe is 10-20% lower than in high income European countries. We evaluated outcome of children and adolescents with rhabdomyosarcoma (RMS) in Slovenia, Croatia, Slovakia and in Romania. Patients and methods We retrospectively analysed event-free survival (EFS) and overall survival (OS) for all patients treated in Slovenia and Croatia. Slovakia included patients from two centers, representing half of expected cases. Romania included patients from single institution, representing only 10% of expected patients. Joint database for analysis was established. Results One hundred seventy-eight children and adolescent with RMS diagnosed from January 2000 to December 2015 were included. Mean patient age at diagnosis was 7.7 years, one third was older than 10 years. Twenty-five percent had alveolar histology and 72% unfavorable location. Higher than expected proportion of patients had nodal involvement (24%) or metastatic disease (27%). All patients received systemic chemotherapy, 57% had radiotherapy and 63% surgery as local control. Kaplan- Meier estimates for 5-year EFS and OS were 50.7% and 59.6%, respectively. Five-year OS for patients with localised disease was 72% compared to 24% for metastatic disease. Conclusions Children with RMS treated in Eastern and Central Europe have inferior outcome compared to their counterparts treated in high income European countries. Active participation of low health expenditures average rates (LHEAR) countries in international clinical trials may improve outcome of paediatric oncology patients.

Invasive Rhino-Orbito-Cerebral Mucormycosis in Pediatric Patient with Acute Leukemia.

BACKGROUND: Invasive fungal infections are a life-threatening complication of cancer treatments, especially in hemato-oncological patients. Mucormycosis is the third leading cause of invasive fungal infections after Aspergillus and Candida infections. The first clinical symptoms are usually non-specific, which can lead to a late diagnosis and delayed therapy. PURPOSE: The objective of this report is to summarize data in the literature about mucormycosis and to present a case report of a patient with acute lymphoblastic leukemia, who developed this infection at our center. Risk factors for the development of mucormycosis, clinical symptoms, radiology, laboratory results, and outcome were retrospectively evaluated. CASE: We describe a 6-years-old female patient with acute lymphoblastic leukemia. During the induction phase of therapy, the patient developed febrile neutropenia and did not respond to therapy with a combination of antibiotics and supportive treatment. Pansinusitis and orbitocellulitis developed. Examination of the biological material revealed that the etiological agent was a Rhizopus sp. The patient was treated with a combination of antimycotic drugs, but the infection disseminated to the central nervous system. She underwent radical surgical resection of the affected tissue. At this time, she is still under treatment with antimycotic and oncology agents, but is in remission of the main diagnosis and in good clinical condition. CONCLUSION: Mucormycosis is an invasive fungal infection with high morbidity and mortality. Early diagnosis and initiation of effective therapy using a combination of amphotericin B administration and surgery are necessary to obtain a favorable outcome. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.