Pediatric Hematology and Oncology最新文献

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.

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.

Opsoclonus-myoclonus syndrome associated with neuroblastoma (OMS-NB) is a refractory paraneoplastic syndrome which often remain neurological sequelae, and detailed pathogenesis has remained elusive. We encountered a pediatric patient with OMS-NB treated by immunosuppressed therapy who showed anti-glutamate receptor δ2 antibody and increased B-cells in cerebrospinal fluid (CSF), and multiple lymphoid follicles containing abundant Bcells in tumor tissue. Unbiased B-cell receptor repertoire analysis revealed identical B-cell clone was identified as the dominant clone in both CSF and tumor tissue. These identical B-cell clone may contribute to the pathogenesis of OMS-NB. Our results could facilitate the establishment of pathogenesis-based treatment strategies for OMS-NB.

The objective of this study was to understand global caregiver concerns about SARS-CoV-2 vaccination for children with cancer and to provide healthcare providers with guidance to support parental decision-making. A co-designed cross-sectional mixed-methods survey was distributed to primary caregivers of children with cancer globally between April and May 2021 via several media. Caregivers were asked to rate the importance of vaccine-related questions and the median scores were ranked. Principal Component Analysis was conducted to identify underlying dimensions of caregiver concerns by World Bank income groups. Content analysis of free-text responses was conducted and triangulated with the quantitative findings. 627 caregivers from 22 countries responded to the survey with 5.3% (n = 67) responses from low-and-middle-income countries (LMIC). 184 caregivers (29%) provided free-text responses. Side effects and vaccine safety were caregivers' primary concerns in all countries. Questions related to logistics were of concern for caregivers in LMIC. A small minority of caregivers (n = 17) did not consider the survey questions important; free-text analysis identified these parents as vaccine hesitant, some of them quoting safety and side effects as main reasons for hesitancy. Healthcare providers and other community organizations globally need to provide tailored information about vaccine safety and effectiveness in pediatric oncology settings. Importantly, continued efforts are imperative to reduce global inequities in logistical access to vaccines, particularly in LMIC.

Iron overload may contribute to long-term complications in childhood cancer survivors. There are limited reports of assessment of tissue iron overload in childhood leukemia by magnetic resonance imaging (MRI). A cross-sectional, observational study in children treated for hematological malignancy was undertaken. Patients ≥6 months from the end of therapy who had received ≥5 red-cell transfusions were included. Iron overload was estimated by serum ferritin (SF) and T2*MRI. Forty-five survivors were enrolled among 431 treated for hematological malignancies. The median age at diagnosis was 7-years. A median of 8 red-cell units was transfused. The median duration from the end of treatment was 15 months. An elevated SF (>1,000 ng/ml), elevated liver iron concentration (LIC) and myocardial iron concentration (MIC) were observed in 5 (11.1%), 20 (45.4%), and 2 (4.5%) patients, respectively. All survivors with SF >1,000 ng/ml had elevated LIC. The LIC correlated with SF (p < 0.001). MIC lacked correlation with SF or LIC. Factors including the number of red-cell units transfused and duration from the last transfusion were associated with elevated SF (p = 0.001, 0.002) and elevated LIC (p = 0.012, 0.005) in multiple linear regression. SF >595 ng/ml predicted elevated LIC with a sensitivity of 85% and specificity of 91.6% (AUC 91.2%). A cutoff >9 units of red cell transfusions had poor sensitivity and specificity of 70% and 75% (AUC 76.6%) to predict abnormal LIC. SF >600 ng/ml is a robust tool to predict iron overload, and T2*MRI should be considered in childhood cancer survivors with SF exceeding 600 ng/ml.

Optimal chemotherapy management is substandard in low and middle-income countries. We aimed to identify major gaps to design interventional strategies for improved chemotherapy management at Tikur Anbessa Specialized Hospital (TASH), Ethiopia. This study was conducted using an observational checklist, open-ended questions, record review, and key informant interviews of department heads and focal persons at TASH. Findings were categorized into specific themes that developed. Chemotherapy represented 60.2% of the hospital medication budget. Drug utilization was quantified via monthly consumption documentation and forecasting. However, unreliable data resulted in frequent stockouts (unavailability of the item when it is needed) of chemotherapy with only 67.8% availability. Thirteen healthcare personnel (9 nurses, 2 pharmacists and 2 hospital cleaners) were interviewed: all clinical staff but neither of hospital cleaners believed that they were at risk of hazardous agents. Challenges identified included inadequate and frequent stockouts (unavailability of the item when it is needed) of personal protective equipment, lack of standardized guidelines for chemotherapy handling, admixture, and disposal, lack of designated preparation rooms, and lack of training. All nine nurses handled chemotherapy admixtures despite only two nurses previously receiving in-service training. Most of the participants had never witnessed the disposal of anticancer drugs. Prompted by the results of this study, a dialogue was initiated among members of TASH, the American Cancer Society and the University of North Carolina to implement action-oriented projects to address the gaps identified at TASH. These gaps directly and indirectly affect care and treatment outcomes of patients at a large cancer center. Collaborations with well-resourced centers are potential models for improving chemotherapy management.

Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. The complete burden and outcomes in Uganda are unknown. The study was a multicenter retrospective chart review of children aged between 0 to 15 years diagnosed with NB from 2010 to 2020. Demographic, clinical and tumor-related characteristics were extracted for analysis. Kaplan-Meier survival curves and Cox regression models were used to determine the one-year overall survival (OS) and identify prognostic factors. Seventy-five patients were evaluated, with a median age at diagnosis of 48 months (IQR 26-108 months). Fever (74.7%), weight loss (74.7%), high blood pressure (70.3%) and abdominal swelling/mass (65.3%) were the most common features at diagnosis. Suprarenal tumors (52%) and stage 4 disease (70.7%) were also common. The one-year OS was 60.0% (95%CI 56.8%; 64.3%) with a median survival time of 12.6 months (95% CI: 8.1; 20.8). The one-year OS for non-metastatic and metastatic disease was 67.3% and 42.6% (p = 0.11) respectively. Leukocytosis (p < 0.001) at diagnosis was of prognostic significance while clinical remission after induction chemotherapy (p < 0.001) provided survival advantages. Children who received maintenance chemotherapy had a longer median survival time of 38.5 months (range 10.8-69.5). Age (p = 0.001), lung metastasis (p < 0.001), and leukocytosis (p < 0.001) remained significant on multivariate analysis. In this Ugandan study, leukocytosis was a clinical predictor of prognosis, metastatic disease had management challenges and maintenance chemotherapy prolonged the survival time but not OS.

Brain tumors are the most common solid tumors in children and a leading cause of cancer-related mortality in children worldwide. Data on the epidemiology and management of pediatric brain tumors in Uganda are limited. We aimed to assess the clinicopathological profile and management of pediatric brain tumors at the national oncology center in Uganda since the inception of weekly multidisciplinary meetings. Records of children younger than19 years diagnosed with primary brain tumors at Uganda Cancer Institute between 2017 and 2021 were retrospectively reviewed. Patient and tumor characteristics were collected with multidisciplinary team management treatment plans for analysis. There were 35 patients evaluated, most of whom were males (57.1%). Craniopharyngioma (n = 9, 25.7%) was the most common brain tumor, followed by astrocytoma (n = 5, 14.2%) and medulloblastoma (n = 4, 11.4%). Management included surgical resection in 28.5% of patients, chemotherapy (28.6%), radiotherapy (17.1%) and palliative care (20.0%). Over the last five years, there were increasing trends in the number of cases discussed in the multidisciplinary team and the number for whom the multidisciplinary management decisions were implemented. The majority (n = 18, 51.4%) of the children with brain tumors were alive and active in care, 34.2% abandoned treatment/lost to follow-up, and 8.6% died. The relative distribution of pediatric brain tumors types in Uganda Cancer Institute differs slightly from international reports, and there has been a notable increase in the number of cases over the years. Implementing multidisciplinary management decisions benefited patients and decreased abandonment and patient loss to follow-up.