Pediatric Hematology and Oncology最新文献

Survival rates for pediatric cancer have significantly increased the past decades, now exceeding 70-80% for most cancer types. The cause of cancer in children and adolescents remains largely unknown and a genetic susceptibility is considered in up to 10% of the cases, but most likely this is an underestimation. Families with multiple pediatric cancer patients are rare and strongly suggestive for an underlying predisposition to cancer. The absence of identifiable mutations in known cancer predisposing genes in such families could indicate undiscovered heritability. To discover candidate susceptibility variants, whole genome sequencing was performed on germline DNA of a family with two children affected by Burkitt lymphoma. Using an inheritance-based filtering approach, 18 correctly segregating coding variants were prioritized without a biased focus on specific genes or variants. Two variants in FAT4 and DCHS2 were highlighted, both involved in the Hippo signaling pathway, which controls tissue growth and stem cell activity. Similarly, a set of nine non-coding variants was prioritized, which might contribute, in differing degrees, to the increased cancer risk within this family. In conclusion, inheritance-based whole genome sequencing in selected families or cases is a valuable approach to prioritize variants and, thus, to further unravel genetic predisposition in childhood cancer.

Survivors of childhood central nervous system (CNS) tumors experience early-onset aging-related phenotypes. DNA methylation (DNAm) age is an emerging epigenetic biomarker of physiologic age and may be predictive of chronic health conditions in long-term survivors. This report describes the course of epigenetic age acceleration using post-diagnosis blood samples (median: 3.9 years post-diagnosis; range: 0.04-15.96) from 83 survivors of pediatric CNS tumors. Epigenetic age acceleration was detected in 72% of patients, with an average difference between chronologic and DNAm age of 2.58 years (95% CI: 1.75-3.41, p < 0.001). Time from diagnosis to sample collection correlated with the magnitude of epigenetic age acceleration.

Announcing drug resistance is complex for pediatric oncologists because they have to provide a substantial amount of medical information while taking a major emotional impact on the parents into account. This study aimed to understand how these announcements are currently conducted and how pediatric oncologists adapt the information given to each family in situations where there is resistance to treatment. Semi-structured interviews were conducted with 15 pediatric oncologists (66.7% women, aged 44.7 years on average). Interviews were audio-recorded and a thematic content analysis was conducted. Announcements of drug resistance are stressful, as they are not well codified, difficult to anticipate, and pediatric oncologists have many issues about how best to behave and which words to choose. The majority of them believe that the severity, or even the incurability of the disease, and the offer of a therapeutic alternative are essential components of the information to pass on. Pediatric oncologists describe how they adapt their communication to each family, particularly in relation to parents' questions, and also to their reactions during the announcement. They also need to adapt to the prior acquaintance they may have with the families, and to previous exchanges. Finally, pediatric oncologists acknowledge their subjectivity when estimating the parents need in terms of information. Understanding the course of these announcements gives us another point of view at the issues involved in this announcement. Proposals to support pediatric oncologists in this difficult moment can be suggested: communication support tool, work in pairs and discussion group.

Sickle cell disease (SCD) is a disease of abnormal hemoglobin associated with severe clinical phenotype and recurrent complications. Hydroxyurea (HU) is one of the US-FDA approved and commonly used drug for the treatment of adult SCD patients with clinical -severity. However, its use in the pediatric groups remains atypical. Despite a high prevalence of the disease in the state Chhattisgarh, there is a lack of evidence supporting its use in pediatric patients. This study aimed to evaluate the pharmacological and clinical efficacy and safety of HU in a large pediatric cohort with SCD from Central India. The study cohort consisted of 164 SCD (138 Hb SS and 26 Hb S beta-thalassemia) children (≤14 years of age) on HU therapy, who were monitored for toxicity, hematological and clinical efficacy at baseline (Pre-HU) and after 24 months (Post-HU). The results highlight the beneficial effects of HU at a mean dose of 18.7 ± 7.0 mg/kg/day. A significant improvement was observed, not only in physical and clinical parameters but also in hematological parameters which include fetal hemoglobin (Hb F), total hemoglobin, hematocrit, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels, when evaluated against the baseline. We did not observe any significant adverse effects during the treatment period. Similar results were obtained on independent analysis of Hb SS and Hb Sβ patients. These findings strengthen the beneficial effect of hydroxyurea in pediatric population also without any serious adverse effects and builds up ground for expanding its use under regular monitoring.

Complementary and alternative medicine (CAM) use in children with cancer has a high prevalence. If (parents of) patients bring up the topic of CAM, pediatric oncologists (POs) face considerable challenges regarding knowledge and professional behavior. In this study, we explore German POs' understanding of CAM and related attitudes as well as challenges and strategies related to CAM discussions by means of semi-structured interviews analyzed according to principles of qualitative thematic analysis with parents of children with cancer. We could conduct 14 interviews prior to theoretical saturation. The interviews had a duration of 15-82 min (M = 30.8, SD = 18.2). Professional experience in pediatric oncology was between 0.5 and 26 years (M = 13.8, SD = 7.6). Main themes identified were a heterogeneous understanding and evaluation of CAM, partly influenced by personal experiences and individual views on plausibility; the perception that CAM discussions are a possible tool for supporting parents and their children and acknowledgement of limitations regarding implementation of CAM discussions; and uncertainty and different views regarding professional duties and tasks when being confronted with CAM as a PO. Our interdisciplinary interpretation of findings with experts from (pediatric) oncology, psychology, and ethics suggests that there is need for development of a consensus on the minimal professional standards regarding addressing CAM in pediatric oncology.

In contrast to the extensive knowledge on EVI1 in myeloid malignancies, few data are available on the EVI1 transcript in pediatric ALL. The purpose of this study was to examine the clinical and biological significance of EVI1 and validate its prognostic significance in pediatric patients with ALL. Here, we examined the clinical and biological significance of EVI1 expression, as measured by real-time polymerase chain reaction (PCR) in 837 children with newly diagnosed ALL treated on the National Protocol of Childhood Leukemia in China (NPCLC)-ALL-2008 protocol, and aimed to explore their prognostic significance in pediatric ALL patients. The EVI1 expression was detected in 27 of 837 (3.2%) patients. No statistically significant differences in prednisone response, complete remission (CR) rates and relapse rates were found between EVI1 overexpression (EVI1⁺) group and EVI1^- group. Moreover, we found no significant difference in event-free survival (EFS) and overall survival (OS) between these two groups, also multivariate analysis did not identify EVI1⁺ as an independent prognostic factor. In the subgroup analysis, there was no difference in clinical outcome between EVI1⁺ and EVI1^- patients in standard‑risk (SR), intermediate-risk (IR) and high-risk (HR) groups. In the minimal residual disease (MRD)<10^-4 group, EVI1⁺ patients have significantly lower EFS and OS rates compared to EVI1^- patients. Further large‑scale and well‑designed prospective studies are required to confirm the results in the future.

During COVID-19, public health measures including masks and social distancing decreased viral upper respiratory infections (URI). Upper respiratory infections are the most common infectious etiology for low-risk pediatric febrile neutropenia (FN). This single-center, quasi-experimental, pre-post study was designed to understand the impact of public health measures on FN admissions and outcomes in the general pediatric oncology population during the COVID (March 2020-February 2021) vs. pre-COVID era (January 2018-February 2020) and their respective respiratory seasons (November-February). Episodes were risk-stratified using a tool recommended by the Children's Oncology Group. Descriptive and bivariate statistics were used to compare admission characteristics and outcomes. Comparing respiratory seasons, the Covid-era season had 60% fewer URI diagnoses (5/12), while high-risk episodes (63.6% [28/44] vs. 44.2% [23/52]) and intensive care admissions (18.2% [8/44] vs. 3.8% [2/52]) increased. Between eras, URIs were lower in the COVID-era (10.8% [16/148] vs. 19.9% [67/336]; p = 0.01), but admission characteristics and severe outcomes were not different. The impact of public health measures was most prominent during the respiratory season. Despite decreased incidence of URIs, the overall admission characteristics and severe outcomes were minimally impacted due to the brevity of respiratory seasons, but larger studies are warranted.

This case reports concomitant use of enzyme and substrate reduction therapy to improve chemotherapy adherence in a pediatric patient diagnosed with Ewing sarcoma (ES) and type 1 Gaucher disease (GD). The 17-year-old female presented with 5 months of right knee pain with associated mass on exam. She was diagnosed with ES with pulmonary metastasis. The patient was treated with 17 alternating cycles of vincristine-doxorubicin-cyclophosphamide and ifosfamide and etoposide chemotherapy followed by tumor resection and radiation per standard protocol. As part of her staging work-up, bone marrow biopsy was performed, significant for Gaucher cells. After the second cycle of chemotherapy the patient began to experience severe delays averaging 30 days between cycles compared to 17.29 days observed in Children's Oncology Group data. Given her bone marrow biopsy findings and chemotherapy delays GD screening was obtained and the patient was diagnosed with GD following genetic confirmation. Due to delays in chemotherapy decreasing chance of remission, the patient was referred to Genetics for aggressive management with imiglucerase and eliglustat. After initiation of therapy the period between chemotherapy cycles decreased to 23 days on average, with a 21% increase in platelet count during therapy. The patient was able to complete ES therapy achieving remission. GD is associated with an increased risk of malignancy, as seen in our patient with ES. GD patients experience prolonged hematologic cytopenia during cancer treatment. Combining Enzyme and Substrate Reduction Therapies should be investigated as an option to improve chemotherapy adherence in GD patients.