Pediatric Acute Lymphoblastic Leukemia Emerging Therapies-From Pathway to Target.

Over the past 40 years, the 5-years-overall survival rate of pediatric cancer reached 75-80%, and for acute lymphoblastic leukemia (ALL), exceeded 90%. Leukemia continues to be a major cause of mortality and morbidity for specific patient populations, including infants, adolescents, and patients with high-risk genetic abnormalities. The future of leukemia treatment needs to count better on molecular therapies as well as immune and cellular therapy. Advances in the scientific interface have led naturally to advances in the treatment of childhood cancer. These discoveries have involved the recognition of the importance of chromosomal abnormalities, the amplification of the oncogenes, the aberration of tumor suppressor genes, as well as the dysregulation of cellular signaling and cell cycle control. Lately, novel therapies that have already proven efficient on relapsed/refractory ALL in adults are being evaluated in clinical trials for young patients. Tirosine kinase inhibitors are, by now, part of the standardized treatment of Ph+ALL pediatric patients, and Blinatumomab, with promising results in clinical trials, received both FDA and EMA approval for use in children. Moreover, other targeted therapies such as aurora-kinase inhibitors, MEK-inhibitors, and proteasome-inhibitors are involved in clinical trials that include pediatric patients. This is an overview of the novel leukemia therapies that have been developed starting from the molecular discoveries and those that have been applied in pediatric populations.

Otitis Media and Obesity-An Unusual Relationship in Children.

Otitis media (OM) represents a public health matter, being the main cause of preventable hearing loss in pediatric patients. Besides well-established risk factors for developing OM, such as craniofacial abnormalities, prematurity, low birth weight, or tobacco exposure, there is evidence that obesity could be associated with a high incidence of OM. Our aim is to perform a literature review on the state of current published research on the relationship between OM and obesity and to discuss the interconnectivity between these two entities. We conducted an electronic search in PubMed and EMBASE databases. Out of 176 references, 15 articles were included in our study. Our findings suggest that obesity and overweight might be risk factors for developing OM, and vice versa. The main mechanisms for developing OM in obese patients include alteration in cytokine profile, increased gastroesophageal reflux, and/or fat accumulation. Conversely, ear infections exposure might increase the risk of obesity, mostly by taste changes through middle ear cavity inflammation.

Outcomes in Pediatric Acute Lymphoblastic Leukemia-A Single-Center Romanian Experience.

BACKGROUND: This study evaluates the main (para)clinical aspects and outcomes in a group of Romanian children diagnosed with acute lymphoblastic leukemia (ALL), under the conditions of antileukemic treatment according to an adapted ALL IC Berlin-Frankfurt-Munster (BFM) 2002 protocol. METHODS: We performed a retrospective single-center study of 125 children diagnosed with ALL between 2010 and 2016. Standard forms were used for data collection of variate clinical and paraclinical parameters. RESULTS: The children were predominantly male (64.8%) and their median age at diagnosis was 5 years. A total of 107 patients were diagnosed with precursor B-cell acute lymphoblastic leukemia (BCP)-ALL and 18 with T-cell acute lymphoblastic leukemia T-ALL. Multiplex reverse transcription polymerase chain reaction RT-PCR assay for ETV6-RUNX1, BCR-ABL, E2A-PBX1, KMT2A-AFF1, and STIL-TAL1 fusion genes was performed in 111 patients. ETV6-RUNX1 translocation was detected in 18.9% of patients, while BCR-ABL1 and E2A-PBX1 rearrangements were seen in 2.7% and 3.6%, respectively. Complete remission at the end of induction phase was obtained in 89.6% of patients. The overall relapse rate was 11.2%, with 11 early and 3 late relapses. The 5-year overall survival rate in BCP-ALL was 81.6% and in T-ALL 71.4%. CONCLUSIONS: The 5-year overall and event-free survival rates in our study were slightly lower than those reported in developed countries, so the patients' outcomes are encouraging.