[THE BENEFIT OF MOLECULAR ANALYSIS USING NEXT GENERATION SEQUENCING METHODS IN PEDIATRIC "HARD TO TREAT" TUMORS - EXPERIENCE IN A TERTIARY MEDICAL CENTER].

INTRODUCTION: While survival rates among children with cancer are high, a significant proportion of the solid tumors are considered as hard to treat (HTT). Next generation sequencing (NGS) offers the ability to detect molecular changes in tumors. Its implementation may allow usage of targeted therapy for tumors that fail to respond to acceptable oncological treatment. Furthermore, these therapies are characterized by milder side effects than chemotherapy. NGS may also aid in establishing pathological diagnoses and occasionally, identifying cancer-predisposition syndromes. However, the benefit of NGS in the pediatric population is not clear. AIMS: Evaluating the benefit of NGS in children with 'HTT' Tumors. METHODS: A retrospective study of the usage of NGS in pediatric 'HTT' in the Department of Pediatric Hemato-Oncology at the Hadassah Medical Center. Patients' demographic and clinical characteristics, molecular changes in tumor, their influence on medical decisions and disease course - were all documented. RESULTS: Forty-seven NGS tests from 'HTT' tumors were completed between January 2018 to August 2020. The results of these tests dictated medical decisions in 18 cases (38.3%) while it proved utility in 10 cases (21.3%). Clinical response to targeted therapy, clarification of diagnosis and identification of germline changes were documented in 3 (6.4%), 4 (8.5%) and 3 (6.4%) cases, respectively. CONCLUSIONS: The usage of NGS may benefit children with 'HTT' and tumors with difficult diagnoses and in some cases may be life-saving. DISCUSSION: Cost-benefit considerations presumably prevent the assimilation of NGS tests in the standard care of pediatric oncology. It is possible that the current results will strengthen the more accurate usage of theses genomic techniques in children with 'HTT'.

Mucormycosis in children with haematological malignancies is a salvageable disease: a report from the Israeli Study Group of Childhood Leukemia.

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but contemporary data in children are lacking. We conducted a nationwide multicentre study to investigate the characteristics of mucormycosis in children with haematological malignancies. The cohort included 39 children with mucormycosis: 25 of 1136 children (incidence 2·2%) with acute leukaemias prospectively enrolled in a centralized clinical registry in 2004-2017, and an additional 14 children with haematological malignancies identified by retrospective search of the databases of seven paediatric haematology centres. Ninety-two percent of mucormycosis cases occurred in patients with acute leukaemias. Mucormycosis was significantly associated with high-risk acute lymphoblastic leukaemia (OR 3·75; 95% CI 1·51-9·37; P = 0·004) and with increasing age (OR 3·58; 95% CI 1·24-9·77; P = 0·01). Fifteen patients (38%) died of mucormycosis. Rhinocerebral pattern was independently associated with improved 12-week survival (OR 9·43; 95% CI 1·47-60·66; P = 0·02) and relapsed underlying malignancy was associated with increased 12-week mortality (OR 6·42; 95% CI, 1·01-40·94; P = 0·05). In patients receiving frontline therapy for their malignancy (n = 24), one-year cumulative mucormycosis-related mortality was 21 ± 8% and five-year overall survival was 70 ± 8%. This largest paediatric population-based study of mucormycosis demonstrates that children receiving frontline therapy for their haematological malignancy are often salvageable.

Modified Transhumeral Amputation: A Case Report.

CASE: A 7-year-old boy presented with osteosarcoma of the ulna that required a transhumeral amputation. The patient completed neoadjuvant chemotherapy before surgery. To prevent bone overgrowth and improved prosthetic fitting, a modified amputation was performed with acute shortening and distal epiphysis preservation. CONCLUSION: In this modified amputation, bone overgrowth was not seen and repeated surgeries for stump shaping were prevented. The modified technique enabled length for the prosthetic elbow and a wide stump for better fitting. In cases of transhumeral amputation in children, the modified technique should be considered.

Bacteremia in Children with Solid Tumors: Etiology, Antimicrobial Susceptibility, Factors Associated with Multidrug Resistance, and Mortality.

This retrospective study aims to describe the etiology and resistance patterns of pathogens causing bacteremia in children with solid tumors in a tertiary pediatric hematology-oncology center in Jerusalem, Israel (2011-2019). Factors associated with multidrug-resistant (MDR) bacteremia and mortality were analyzed. A total of 228 pathogens were isolated in 126 patients; 61.0% were gram-negative rods (GNR) and 38.2% were gram-positive cocci (GPC). The most common pathogens were Klebsiella pneumoniae (19.3%), Escherichia coli (17.5%), and coagulase-negative staphylococci (16.2%). The proportion of MDR-GNR was 18.2%, while the proportion of MDR-GPC was 55.2%. In logistic regression analysis, breakthrough bacteremia on a penicillin-group antibiotic (odds ratio [OR] 5.69, [95% confidence interval 1.42-22.76], p-value = 0.014) was associated and underlying diagnosis of neuroblastoma was inversely associated (OR 0.17, [0.04-0.81], p-value = 0.026) with MDR-GNR bacteremia; while the previous hospitalizations' duration (OR 1.032/day, [1.01-1.06], p-value = 0.007) and oncologic treatment intensity (OR 2.19, [1.08-4.45, p-value = 0.03) were associated with MDR-GPC bacteremia. Shock, prolonged profound neutropenia, and pediatric intensive care unit (PICU) admission were associated with 7-day mortality; and relapsed disease, oncologic treatment intensity, prolonged profound neutropenia, and PICU admission-with 30-day mortality in the univariate analyses. Empirical antibiotic choice should be based on factors associated with MDR infections in this specific population.