Acute lymphoblastic leukemia is the most common blood cancer in pediatric patients. There has been enormous progress in ALL treatment in recent years, which is reflected by the increase in the 5-year OS from 57% in the 1970s to up to 96% in the most recent studies. ALL treatment is based primarily on conventional methods, which include chemotherapy and radiotherapy. Their main weakness is severe toxicity, which prompts dose reduction, decreases the effectiveness of the treatment, and, in some cases, can lead to death. Currently, numerous modifications in treatment regimens are applied in order to limit toxicities emerging from conventional approaches and improve outcomes. Hematological treatment of pediatric patients is reaching for more novel treatment options, such as targeted treatment, CAR-T-cells therapy, and immunotherapy. These methods are currently used in conjunction with chemotherapy. Nevertheless, the swift progress in their development and increasing efficacity can lead to applying those novel therapies as standalone therapeutic options for pediatric ALL.

Epilepsy is a chronic disease of the central nervous system characterized by recurrent epileptic seizures. As a result of epileptic seizure or status epilepticus oxidants are excessively formed, which may be one of the causes of neuronal death. Given the role of oxidative stress in epileptogenesis, as well as the participation of this process in other neurological conditions, we decided to review the latest state of knowledge regarding the relationship between selected newer antiepileptic drugs (AEDs), also known as antiseizure drugs, and oxidative stress. The literature review indicates that drugs enhancing GABA-ergic transmission (e.g., vigabatrin, tiagabine, gabapentin, topiramate) or other antiepileptics (e.g., lamotrigine, levetiracetam) reduce neuronal oxidation markers. In particular, levetiracetam may produce ambiguous effects in this regard. However, when a GABA-enhancing drug was applied to the healthy tissue, it tended to increase oxidative stress markers in a dose-dependent manner. Studies on diazepam have shown that it exerts a neuroprotective effect in a “U-shaped” dose-dependent manner after excitotoxic or oxidative stress. Its lower concentrations are insufficient to protect against neuronal damage, while higher concentrations produce neurodegeneration. Therefore, a conclusion follows that newer AEDs, enhancing GABA-ergic neurotransmission, may act similarly to diazepam, causing neurodegeneration and oxidative stress when used in high doses.

The view of paediatric cancer as a genetic disease arises as genetic research develops. Germline mutations in cancer predisposition genes have been identified in about 10% of children. Paediatric cancers are characterized by heterogeneity in the types of genetic alterations that drive tumourigenesis. Interactions between germline and somatic mutations are a key determinant of cancer development. In 40% of patients, the family history does not predict the presence of inherited cancer predisposition syndromes and many cases go undetected. Paediatricians should be aware of specific symptoms, which highlight the need of evaluation for cancer syndromes. The quickest possible identification of such syndromes is of key importance, due to the possibility of early detection of neoplasms, followed by presymptomatic genetic testing of relatives, implementation of appropriate clinical procedures (e.g., avoiding radiotherapy), prophylactic surgical resection of organs at risk, or searching for donors of hematopoietic stem cells. Targetable driver mutations and corresponding signalling pathways provide a novel precision medicine strategy.Therefore, there is a need for multi-disciplinary cooperation between a paediatrician, an oncologist, a geneticist, and a psychologist during the surveillance of families with an increased cancer risk. This review aimed to emphasize the role of cancer-predisposition gene diagnostics in the genetic surveillance and medical care in paediatric oncology.

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. Despite the enormous progress in ALL therapy, resulting in achieving a 5-year survival rate of up to 90%, the ambitious goal of reaching a 100% survival rate is still being pursued. A typical ALL treatment includes three phases: remission induction and consolidation and maintenance, preceded by a prednisone prephase. Poor prednisone response (PPR) is defined as the presence of ≥1.0 × 109 blasts/L in the peripheral blood on day eight of therapy and results in significantly frequent relapses and worse outcomes. Hence, identifying risk factors of steroid resistance and finding methods of overcoming that resistance may significantly improve patients’ outcomes. A mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK-ERK) pathway seems to be a particularly attractive target, as its activation leads to steroid resistance via a phosphorylating Bcl-2-interacting mediator of cell death (BIM), which is crucial in the steroid-induced cell death. Several mutations causing activation of MAPK-ERK were discovered, notably the interleukin-7 receptor (IL-7R) pathway mutations in T-cell ALL and rat sarcoma virus (Ras) pathway mutations in precursor B-cell ALL. MAPK-ERK pathway inhibitors were demonstrated to enhance the results of dexamethasone therapy in preclinical ALL studies. This report summarizes steroids’ mechanism of action, resistance to treatment, and prospects of steroids therapy in pediatric ALL.

sclerosis in a child with neurofibromatosis type Iclinical management of a challenging case. Ann Agric Environ Med.