There is scanty information about invasive aspergillosis (IA) in the pediatric population. A review of IA at Hospital Infantil Universitario Niño Jesús between 1996 and 2006 was undertaken to analyze incidence, risk factors, and treatment response. Twenty patients were diagnosed with probable or proven IA during the study period, with a cumulative incidence of 1.96%. Incidence was higher in hematopoietic stem cell transplantation (HSCT) recipients: 2.26% (3.5% in allogeneic HSCT and 1.2% in autologous HSCT). A significative increase in IA incidence was observed along the study period (P=0.013), although this increase did not reach signification if only proven cases were compared (P=0.058). Most patients presented multiple risk factors for IA (87% more than 1, and 47% more than 3). The most frequently described risk factor was chemotherapy (90%), after by long-term neutropenia (90%), and corticotherapy (75%). Main locations of the infection were pulmonary (8 patients), cutaneous (3 patients) and intestinal (3 patients). Six patients presented disseminated IA. Initial response to treatment was 55%, although 3 of these cases had a subsequent episode. Global antifungal response, at the end of the follow-up, was 45%. IA-related mortality was 55%. Global mortality was 90%. Only 2 patients (isolated cutaneous IA cases) survived. Seven patients died due to their underlying malignant disease without active fungal disease. Incidence of IA in oncology children is increasing, and in adults. In our experience, IA is a marker of poor outcome even for patients who initially respond to antifungal treatment.

Neuroblastoma is the most common extracranial solid tumour in children, accounting for 15% of all paediatric cancer deaths. High-risk neuroblastoma is a particularly challenging-to-treat form of disease that requires multimodality treatment, consisting of chemotherapy, surgery, high-dose chemotherapy with autologous haematopoietic stem cell rescue, radiotherapy and differentiation therapy. However, despite intense multimodal treatment regimens, the prognosis for this patient population remains poor. In recent years, immunotherapy with anti-disialoganglioside 2 (anti-GD2) antibodies was found to improve survival rates for patients with high-risk neuroblastoma. Based on studies led by the SIOPEN (International Society of Paediatric Oncology European Neuroblastoma) group, the anti-GD2 antibody dinutuximab beta was approved for use in high-risk neuroblastoma by the European Medicines Agency and has been implemented into the standard of care in many countries across Europe. However, immunotherapy with dinutuximab beta is associated with a number of adverse events that may be challenging for clinicians, such as pain, fever, hypersensitivity reactions and capillary leak syndrome. While these adverse events are considered manageable, there are currently no formal guidelines to support clinicians with their management. The aim of this article is to discuss the management of the most common adverse events encountered in clinical practice and to provide practical guidance to assist clinicians in minimising toxicity associated with dinutuximab beta.

Neuroblastoma causes 15% of cancer mortality in children. High risk neuroblastoma has poor prognosis, with high relapse rate and mortality despite multimodal treatment. 123-I-meta-iodo-benzyl-guanidine (mIBG) scintigraphy is one of the current standard diagnostic procedures in neuroblastoma. mIBG can also be used therapeutically, labeled with 131-I, as a radiopharmaceutical agent, delivering targeted radiotherapy to tumoral sites. But published data of this strategy show heterogeneous results. One concern is that in most reports the infused activity is only based in body-weight, which could lead to infra or over-treatment, depending on inter-patient variability in radiation absorption. Activity adjustment by whole-body dosimetry can be used to homogeneize the treatment. Also, mIBG avid tumors may lose avidness along the treatment. As mIBG is used both for treatment and response evaluation, this could result in undetected progressions in patients with apparent complete response. We present a retrospective single-center review of neuroblastoma patients who received therapeutic 131-I-mIBG, focusing on cases with dosimetry-adjusted activity. Dosimetry allowed for a more precise delivery of radiation, reducing 81.1% of deviation from absorption target of 4 Gray (Gy), from 23.4% (±0.936 Gy) to 4.4% (± 0.176 Gy). Patients who showed partial or complete response had better and longer survival. Relapse/progression in non-responders was an early event (within 3 months from treatment). We also present one case of progression with apparent complete response due to loss of mIBG avidness, detected in our series.

Purpose: Outcome for children with refractory and relapse/progressive high-risk neuroblastoma (HR-NB) remains poor, without an internationally agreed standard second-line approach. Heterogeneity in patients’ disease and treatment strategies challenges clinical management. The survival rate for patients with resistant disease does not exceed 20% at 5 years. The study’s aim was to analyze refractory and progressive HR-NB patients in a real-world setting to evaluate current clinical practices and optimize future approaches. Methods: Data from patients diagnosed with refractory and relapse/progressive (R/R-P) HR-NB between January 2019 and December 2021 at six of the major Spanish neuroblastoma treating hospitals were collected and analyzed. Results: A total of 67 episodes of R/R-P HR-NB were included. Treatments applied included chemotherapy (97%), immunotherapy (48%), consolidation (21%), local treatment (surgery and/or radiotherapy) (45%) and maintenance (16%), and were administered within a clinical trial (CT) in 34% of the episodes. Biopsy was performed in 37% of the tumors and 30% were profiled. Event-free survival (EFS) in our cohort was 20.9% and overall survival (OS) 32%. Significant survival advantage (in both OS and EFS) was observed in refractory episodes compared to relapse/progressive, in first events compared to successive, and when response or disease stabilization was achieved. MYCN status, presence of lymph node metastases, use of irinotecan or topotecan, and radiotherapy were also univariate predictors of OS. Conclusions: Treatment of refractory and relapse/progressive HR-NB is highly heterogeneous. We confirm a poor outcome, although certain epidemiological and treatment-related factors have prognostic value. Molecular profiling and inclusion in CTs should be improved.

Malignant bone tumors are aggressive tumors, with a high tendency to metastasize, that are observed most frequently in adolescents during rapid growth spurts. Pediatric patients with malignant bone sarcomas, Ewing sarcoma and osteosarcoma, who present with progressive disease have dire survival rates despite aggressive therapy. These therapies can have long-term effects on bone growth, such as decreased bone mineral density and reduced longitudinal growth. New therapeutic approaches are therefore urgently needed for targeting pediatric malignant bone tumors. Harnessing the power of the immune system against cancer has improved the survival rates dramatically in certain cancer types. Natural killer (NK) cells are a heterogeneous group of innate effector cells that possess numerous antitumor effects, such as cytolysis and cytokine production. Pediatric sarcoma cells have been shown to be especially susceptible to NK-cell-mediated killing. NK-cell adoptive therapy confers numerous advantages over T-cell adoptive therapy, including a good safety profile and a lack of major histocompatibility complex restriction. NK-cell immunotherapy has the potential to be a new therapy for pediatric malignant bone tumors. In this manuscript, we review the general characteristics of osteosarcoma and Ewing sarcoma, discuss the long-term effects of sarcoma treatment on bones, and the barriers to effective immunotherapy in bone sarcomas. We then present the laboratory and clinical studies on NK-cell immunotherapy for pediatric malignant bone tumors. We discuss the various donor sources and NK-cell types, the engineering of NK cells and combinatorial treatment approaches that are being studied to overcome the current challenges in adoptive NK-cell therapy, while suggesting approaches for future studies on NK-cell immunotherapy in pediatric bone tumors.