Developing CAR T-Cell Therapies for Pediatric Solid Tumors.

Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematological malignancies, inducing notable and durable clinical responses. However, for solid tumors, including but not limited to pediatric tumors, several peculiar biological features posed substantial challenges for achieving comparable results. Despite sound pre-clinical evidence of the ability of CAR T cells to eradicate solid malignancies, their activity remains suboptimal when facing the in vivo complexity of solid tumors, characterized by antigen heterogeneity, scarce T-cell infiltration, and an immunosuppressive microenvironment.

Case report: A safeguard in the sea of variants of uncertain significance: a case study on child with high risk neuroblastoma and acute myeloid leukemia.

The increased availability of genetic technologies has significantly improved the detection of novel germline variants conferring a predisposition to tumor development in patients with malignant disease. The identification of variants of uncertain significance (VUS) represents a challenge for the clinician, leading to difficulties in decision-making regarding medical management, the surveillance program, and genetic counseling. Moreover, it can generate confusion and anxiety for patients and their family members.

Venetoclax plus cyclophosphamide and topotecan in heavily pre-treated relapsed metastatic neuroblastoma: a single center case series.

The prognosis of relapsed/refractory (R/R) neuroblastoma (NB) is dismal, calling for new therapeutic strategies. Venetoclax (VEN) is a highly selective, potent, orally bioavailable, BCL-2 inhibitor small-molecule that showed a synergistic effect with cyclophosphamide and topotecan (Cy-Topo) in murine NB models. Our aim was to evaluate the feasibility of VEN plus Cy-Topo in children with R/R NB.

Genetic Predisposition to Hematologic Malignancies in Childhood and Adolescence.

Advances in molecular biology and genetic testing have greatly improved our understanding of the genetic basis of hematologic malignancies and have enabled the identification of new cancer predisposition syndromes. Recognizing a germline mutation in a patient affected by a hematologic malignancy allows for a tailored treatment approach to minimize toxicities. It informs the donor selection, the timing, and the conditioning strategy for hematopoietic stem cell transplantation, as well as the comorbidities evaluation and surveillance strategies.

Safety and Efficacy of Mek Inhibitors in the Treatment of Plexiform Neurofibromas: A Retrospective Study.

Introduction: Plexiform neurofibromas (PN) represent the main cause of morbidity in patients affected by Neurofibromatosis Type 1 (NF1). Until recently, surgery has been the main treatment option in these patients, but it is burdened with a low efficacy rate and a high incidence of side effects as well as recurrence. In recent years, MEK inhibitors (MEKi) such as selumetinib and trametinib have shown great promise.

Case report: A new pathogenic variant of LRBA deficiency with a complex phenotype and Rosai-Dorfman disease.

We reported a new pathogenic variant of LRBA deficiency with a complex phenotype-neonatal diabetes, very early-onset inflammatory bowel disease, and polyarthritis-who presented with lymph node enlargement. A case of Rosai-Dorfman's disease (RDD) was confirmed. The occurrence of an RDD lesion in LRBA-deficiency has never been reported so far.

The Pitfall of Ganglioneuroblastoma-Nodular Diagnosis: Clinical and Imaging Considerations over a Rare Bifocal Sporadic Case.

Neuroblastic tumors (NTs) represent the most common extracranial neoplasm occurring in childhood. Although ganglioneuroblastoma intermixed (GNBI) and ganglioneuroma (GN) are classified as very low-risk tumors, neuroblastoma (NB) and ganglioneuroblastoma-nodular (GNBN) may represent a serious risk to survival. Unfortunately, areas of GNBI and GNBN can coexist in the same mass, leading to incorrect risk staging when only biopsy is performed.

Central Nervous System Metastasis in Neuroblastoma: From Three Decades Clinical Experience to New Considerations in the Immunotherapy Era.

Central nervous system (CNS) metastatic spread in neuroblastoma (NB) is rare and occurs more often at relapse/progression. We report on CNS involvement in high risk (HR) NB over 25 years. For this retrospective study, we reviewed the CNS imaging of all the patients treated at Bambino Gesù Children Hospital from 1 July 1996 to 30 June 2022.

Cerebellar mutism syndrome: From pathophysiology to rehabilitation.

Cerebellar mutism syndrome (CMS) is a common complication following surgical resection of childhood tumors arising in the posterior fossa. Alteration of linguistic production, up to muteness and emotional lability, generally reported at least 24 h after the intervention, is the hallmark of post-operative CMS. Other associated traits include hypotonia and other cerebellar motor signs, cerebellar cognitive-affective syndrome, motor deficits from the involvement of the long pathways, and cranial neuropathies.

Multidisciplinary Management of Craniopharyngiomas in Children: A Single Center Experience.

Background: Craniopharyngioma (CP) is a rare brain tumor involving the sellar region. The best management is still debated. Gross total resection (GTR) is considered the best option to improve recurrence-free survival, but considerable long-term sequelae with a significant impact on quality of life have been reported.

Pediatric Diffuse Midline Gliomas: An Unfinished Puzzle.

Diffuse midline glioma (DMG) is a heterogeneous group of aggressive pediatric brain tumors with a fatal prognosis. The biological hallmark in the major part of the cases is H3K27 alteration. Prognosis remains poor, with median survival ranging from 9 to 12 months from diagnosis.

Common bone marrow signature in COVID-19-associated multisystem inflammatory syndrome in children: A first-wave small case series experience.

The hyper-inflammatory response, also known as multisystem inflammatory syndrome in children (MIS-C), represents a major concern in children with SARS-CoV-2 infection. We report bone marrow features of three patients with MIS-C who were diagnosed during the first wave of the SARS-CoV-2 pandemic. A bone marrow evaluation was performed at onset of the inflammatory condition in order to exclude secondary hemophagocytic lymphohistiocytosis (sHLH).

Liquid Biopsy with Detection of NRAS Mutation in Cerebrospinal Fluid: An Alternative Tool for the Diagnosis of Primary Pediatric Leptomeningeal Melanoma.

Primary leptomeningeal melanoma (PLMM) is a very rare disease in childhood with a poor prognosis. NRAS mutation frequently drives malignant transformation in this population, so its evaluation should be considered in childhood PLMM diagnosis. In the presented case, the mutation was detected by Sanger sequencing performed on DNA extracted from cerebrospinal fluid neoplastic cells.

GATA 2 Deficiency: Focus on Immune System Impairment.

GATA2 deficiency is a disease with a broad spectrum of clinical presentation, ranging from lymphedema, deafness, pulmonary dysfunction to miscarriage and urogenital anomalies, but it is mainly recognized as an immune system and bone marrow disorder. It is caused by various heterozygous mutations in the gene, encoding for a zinc finger transcription factor with a key role for the development and maintenance of a pool of hematopoietic stem cells; notably, most of these mutations arise . Patients carrying a mutated allele usually develop a loss of some cell populations, such as B-cell, dendritic cell, natural killer cell, and monocytes, and are predisposed to disseminated human papilloma virus and mycobacterial infections.

Gaps and Opportunities of Artificial Intelligence Applications for Pediatric Oncology in European Research: A Systematic Review of Reviews and a Bibliometric Analysis.

The application of artificial intelligence (AI) systems is emerging in many fields in recent years, due to the increased computing power available at lower cost. Although its applications in various branches of medicine, such as pediatric oncology, are many and promising, its use is still in an embryonic stage. The aim of this paper is to provide an overview of the state of the art regarding the AI application in pediatric oncology, through a systematic review of systematic reviews, and to analyze current trends in Europe, through a bibliometric analysis of publications written by European authors.

The Fight Just Born-Neonatal Cancer: Rare Occurrence with a Favorable Outcome but Challenging Management.

The occurrence of cancer in newborns within the first 28 days of life is uncommon, with different clinical presentation from other age groups. Prenatal diagnosis is reported in about half of patients, while a genetic predisposition condition is supposed. The management of a newborn with cancer can be challenging and needs to be tailored according to the histology and the primary tumor site; surgery represents the main strategy, while chemotherapy should be considered with caution because of the higher toxicity and mortality due to different pharmacokinetics in neonates compared to older children.