Pediatric Oncology Centers Research Articles

Role of cytogenetic profiles as prognostic factors for complete remission after induction phase in acute myeloblastic leukemia

Background Risk stratification for acute myeloid leukemia (AML) in children is a must in treatment strategy. This stratification is based on cytogenetic profiles, which are needed to determine proper management to gain better outcomes and reduce side effects of treatment. There is no such risk stratification available in Indonesia until now.
 Objective To evaluate the association between cytogenetic profiles of t(8,21) and inv(16) mutations with the complete response to induction phase of chemotherapy in pediatric AML.
 Methods A prospective study was conducted between year 2018 and 2020, involving children with AML from 4 pediatric oncology centers in Jakarta. Subjects were evaluated for cytogenetic profiles, especially t(8,21) and inv(16), as the favorable predictors for AML. Bone marrow remission was evaluated after 2 cycles of induction phase. The results were evaluated for remission rate and survival analysis.
 Results Karyotype data of 18 subjects were obtained. Translocation t(8;21) detected in 1 subject, and inv(16) mutation in 4 subjects. These two variables had no significant correlation with complete remission after induction phase. Nevertheless, favorable group had more tendencies to achieved remission than unfavorable group. Complete remission achieved in 61% subjects, 90% of theme had a relapse period with an average time 43 weeks. The relapse period in favorable group was shoter than in unfavorable group (34 weeks and 44 weeks, respectively).
 Conclusions This study shows that cytogenetic profiles of t(8;21) and inv(16) mutation can not be used as prognostic factors for complete remission after induction phase of chemotherapy in pediatric AML.

Challenges of paediatric palliative care in Romania: a focus groups study

BackgroundThe availability of palliative care facilities for children vary considerably among the European member states. In Romania, a country where health expenditure is among the lowest in Europe, palliative care has been mainly provided by charitable organizations. Despite the high number of children needing palliative care, there is scant literature and research available on paediatric palliative care in Romania. The study explores the viewpoints of various paediatric oncology providers with regard to paediatric palliative care provision in Romania.MethodsFour mixed focus groups were conducted at four university-affiliated paediatric oncology centres located in three distinct Romanian regions (Bucuresti-llfov, Nord-Est and Nord-Vest). The focus groups were analyzed using thematic coding.ResultsFor many healthcare professionals, emotional burden inherent to the profession; unhealthy work-life balance and understaffing were among the biggest barriers to the successful integration of pediatric palliative care. The lack of staff was attributed to a shortage of financial resources, and to the persisting cultural stigma surrounding palliative care and oncology. Also political turmoil was identified as an important obstacle to palliative care implementation.ConclusionSignificant barriers persist limiting the broader implementation of pediatric palliative care in Romania. In order to render palliative care in pediatric oncology more sustainable, more attention should be paid to the mental health care of healthcare professionals working in this field, to the development of mobile palliative care services and to the emigration of skilled medical staff.

Assessment of Arsenic Trioxide and All-trans Retinoic Acid for the Treatment of Pediatric Acute Promyelocytic Leukemia

All-trans retinoic acid (ATRA) and arsenic trioxide therapy without the use of maintenance therapy has been found to be beneficial for the treatment of adults with standard-risk acute promyelocytic leukemia (APL). However, it is unclear whether similar regimens are safe and beneficial for the treatment of high-risk APL or pediatric patients with standard-risk APL. To assess whether treatment with an ATRA and arsenic trioxide-based regimen is safe and allows for the elimination or substantial reduction of chemotherapy use among pediatric patients with standard-risk or high-risk APL, respectively. The Children's Oncology Group AAML1331 study is a nonrandomized, noninferiority trial that examined survival outcomes among 154 pediatric patients with APL compared with a historical control group of patients with APL from the AAML0631 study. Patients aged 1 to 21 years were enrolled at 85 pediatric oncology centers (members of the Children's Oncology Group) in Australia, Canada, and the US from June 29, 2015, to May 7, 2019, with follow-up until October 31, 2020. All patients had newly diagnosed APL and were stratified into standard-risk APL (white blood cell count <10 000/μL) and high-risk APL (white blood cell count ≥10 000/μL) cohorts. All patients received ATRA and arsenic trioxide continuously during induction therapy and intermittently during 4 consolidation cycles. Patients with high-risk APL received 4 doses of idarubicin during induction therapy only. The duration of therapy was approximately 9 months, and no maintenance therapy was administered. Event-free survival (EFS) at 2 years after diagnosis. Among 154 patients (median age, 14.4 years [range, 1.1-21.7 years]; 81 male participants [52.6%]) included in the analysis, 98 patients (63.6%) had standard-risk APL, and 56 patients (36.4%) had high-risk APL. The median follow-up duration was 24.7 months (range, 0-49.5 months) for patients with standard-risk APL and 22.8 months (range, 0-47.7 months) for patients with high-risk APL. Patients with standard-risk APL had a 2-year EFS rate of 98.0% and an overall survival rate of 99.0%; adverse events included 1 early death during induction therapy and 1 relapse. Patients with high-risk APL had a 2-year EFS rate of 96.4% and an overall survival rate of 100%; adverse events included 2 relapses and 0 deaths. These outcomes met predefined noninferiority criteria (noninferiority margin of 10% among those with standard-risk APL and 14.5% among those with high-risk APL). In this nonrandomized, noninferiority trial, pediatric patients with standard-risk APL who received treatment with a chemotherapy-free ATRA and arsenic trioxide regimen experienced positive outcomes. Patients with high-risk APL also had positive outcomes when treated with a novel ATRA and arsenic trioxide-based regimen that included 4 doses of idarubicin during induction therapy only and no maintenance therapy. The 2-year EFS estimates were noninferior to the historical comparator group, and advantages of the regimen included shorter treatment duration, lower exposure to anthracycline and intrathecal chemotherapy, and fewer days hospitalized. ClinicalTrials.gov Identifier: NCT02339740.

Physical activity levels, exercise preferences, and exercise barriers in Korean children and adolescents after cancer treatment.

The purpose of the current study was to explore physical activity (PA) levels, exercise preferences, and perceived barriers to PA in childhood cancer survivors. This cross-sectional study surveyed 120 childhood cancer survivors aged 8-18years from the pediatric oncology center in South Korea between March and August 2017. The modified Exercise & Quality of Life questionnaire, Korea Youth Risk Behavior Web-based Survey, and Godin Leisure-Time Questionnaire were used to assess PA levels, preferences, and exercise barriers. Among 120 participants (72 boys, 48 girls) whose average age at the time of the survey was 14.57 ± 3.00years and the average age at diagnosis was 8.22years, the three most common diagnoses were acute leukemia (43.3%), brain tumor (13.3%), and malignant lymphoma (10.8%). Only 16 participants (5%) met the PA recommendations for children (at least 60min of moderate PA per day). The most preferred sporting activities included soccer, basketball, strengthening exercises, badminton, dance, and taekwondo. They generally had positive attitudes toward exercise, and more than 63% of participants intended to exercise the following month. The five most prevalent perceived barriers to exercise were lack of time, poor health, reluctance to sweat, lack of exercise skills, and no exercise partners. While most childhood cancer survivors did not meet the PA recommendation, most of them agreed that exercise was beneficial, and they intended to participate in the exercise. Exercise and PA programs should be tailored to the personal health and preferences of childhood cancer survivors.

Childhood head trauma and the risk of childhood brain tumours: A case-control study in Ontario, Canada.

Head trauma in early childhood has been hypothesized as a potential risk factor for childhood brain tumours (CBTs). However, head trauma has not been extensively studied in the context of CBTs and existing studies have yielded conflicting results. A population-based and hospital-based case-control study of children 0 to 15 years with newly diagnosed CBTs from 1997 to 2003 recruited across Ontario through paediatric oncology centres was conducted. Controls were frequency-matched with cases by age, sex and geographical region. The association was assessed based on multivariable logistic regressions, accounting for child's age, sex, ethnicity, highest level of maternal education and maternal pack-years of smoking during the pregnancy. Analyses were conducted separately based on age of first head trauma, sex and histology. A latency period analysis was conducted. Overall, based on 280 cases and 919 controls, CBTs were not significantly associated with previous history of head trauma (OR 1.34, 95% CI 0.96, 1.86), head trauma severity, number of head injuries, or head or neck X-rays or computed tomography (CT) examinations. Results were consistent across sexes and histological subtypes. However, head trauma within the first year of life was significantly associated with CBTs (OR 2.00, 95% CI 1.01, 3.98), but the association diminished when adjusted for X-ray or CT occurring during the same time period (OR 1.62, 95% CI 0.75, 3.49), albeit limited sample size. Overall, no association was observed between head trauma and CBTs among all children, while head trauma occurring within first year of life may warrant further investigation in future research.

How can fertility counseling be implemented for every newly diagnosed pediatric patient facing gonadotoxic treatment?-A single-center experience

Since the survival rates of pediatric patients undergoing cancer treatment or hematopoietic stem cell transplantation (HSCT) have increased rapidly in recent decades, the late effects of treatment are now an important focus of patient care. Access to fertility preservation (FP) procedures as well as their financing differs considerably across Europe. However, some countries in Europe have recently changed the legal basis for financing FP procedures; therefore, the implementation of structures is mandatory to give patients access to FP. In this prospective cohort study, we characterized the process for establishing pediatric fertility counseling, including the development of an in-house standard procedure for recommendations regarding FP with potentially gonadotoxic treatment and valuating data from all FP counseling sessions. All data concerning patient characteristics (pubertal status, disease group) and recommendation of FP measures were prospectively collected and adoption of FP measures analyzed. Prior to the establishment of a structured process for FP in our pediatric oncology and stem cell transplantation center, there was no standardized FP counseling. We demonstrate that with the establishment of an inhouse standard procedure, it is possible to give consistent yet individualized FP counseling to approximately 90% of our patients facing gonadotoxic treatment, counseling over 200 patients between 2017 and 2019. This pilot study could potentially be adapted in other pediatric hematology, oncology, and stem cell transplantation centers to allow a more standardized handling of FP counseling for all patients facing gonadotoxic treatment.

Small steps towards bigger goals: A study of demography and outcome of paediatric cancers in a peripheral resource limited paediatric oncology centre

Background: The aim of this study was to analyze the demography, clinical profile and outcome of pediatric cancer cases from a peripheral resource limited center.Methods: We retrospectively analysed demography, clinical details and outcomes of 227 cases of paediatric cancer up to nineteen years of age, from August 2009 to May 2019. Their status of treatment was categorised as completed, ongoing, abandoned and expired. We generated Kaplan-Meier curves (KM) and calculated three-year event free survival (EFS) and overall survival (OS).Results: Out of 227 children, 139 (61.2%) were boys and the rest were girls. Maximum number of children 108 (47.6%) were aged zero to four years. The socioeconomic status of 70 patients using the Kuppuswammy scale showed that 55 patients (78.57%) belonged to a lower socio-economic stratum. The commonest malignancy was leukaemia 119(52.4%) followed by solid tumours constituting 84 (37%) patients, of which 25 (11.01%) were renal tumours. Out of total 227 patients, 107 (47.13%) have completed treatment, 45 (19.8%) were on treatment, 24 (10.6%) have abandoned and 51 (22.5%) had expired. The median duration of follow up was 18 months. The three-year EFS and OS were 71.9% and 74.8% respectively for the entire COHORT, 74.4% and 75.5% for ALL (Acute Lymphocytic Leukemia), 38.4% and 46.1% for AML (Acute Myeloid Leukemia) and 74.3% and 76.6% for solid tumours. Among solid tumours, three-year EFS and OS was of renal tumours 86.9% and of neuroblastoma was 77.7%.Conclusions: We achieved outcomes similar to those from well-established Indian single institute studies. The survival of our paediatric cancer patients can be improved with collaborative effort and establishment of new centres in the periphery.

SARS‐CoV‐2 in children with cancer in Brazil: Results of a multicenter national registry

BackgroundStrategies to mitigate the impact of COVID‐19 in special populations are complex and challenging. Few studies have addressed the impact of COVID‐19 on pediatric patients with cancer in low‐ and middle‐income countries.MethodsMulticenter observational cohort study with prospective records and retrospective analyses starting in April 2020 in 21 pediatric oncology centers distributed throughout Brazil. Participants: Patients under 18 years of age who are infected by the SARS‐CoV‐2 virus (confirmed diagnosis through reverse transcriptase‐polymerase chain reaction [RT‐PCR]) while under treatment at pediatric oncology centers. The variables of interest included clinical symptoms, diagnostic and therapeutic measures. The repercussions of SARS‐CoV‐2 infection on cancer treatment and general prognosis were monitored.ResultsOne hundred seventy‐nine patients were included (median age 6 [4–13] years, 58% male). Of these, 55.9% had acute leukemia and 34.1% had solid tumors. The presence of SARS‐CoV‐2 was diagnosed by RT‐PCR. Various laboratory markers were analyzed, but showed no correlation with outcome. Children with low or high BMI for age had lower overall survival (71.4% and 82.6%, respectively) than those with age‐appropriate BMI (92.7%) (p = .007). The severity of presentation at diagnosis was significantly associated with outcome (p < .001). Overall mortality in the presence of infection was 12.3% (n = 22).ConclusionIn children with cancer and COVID‐19, lower BMI was associated with worse prognosis. The mortality in this group of patients (12.3%) was significantly higher than that described in the pediatric population overall (∼1%).

Meropenem Use in Pediatric Oncology - Audit on Indication, Appropriateness and Consumption Comparing Patient Derived and Pharmacy Dispensing Data.

Meropenem is an important second- or third-line antibiotic in pediatric cancer patients with febrile neutropenia (FN). Concise utilization data of meropenem in this setting is limited. It remains unclear how drug dispensing data from the hospital pharmacy correlate with data derived from patients' files. Retrospective audit of meropenem-consumption in a University-affiliated pediatric oncology center in days of therapy (DOT)/100 inpatient days. The individual indication for meropenem was critically reviewed. The real consumption (in g/100 inpatient days) was compared with the drug amounts dispensed by the hospital pharmacy (in gram and in defined daily doses (DDD)/100 inpatient days). All patients receiving at least one dose of meropenem from 1st of April 2016 until the 30th of June 2018 were included. Of 235 consecutive patients, 45 (19%) received meropenem, comprising 57 FN events. The probability of receiving at least one dose of meropenem was significantly higher in patients with ALL, AML, NHL and certain CNS tumors. Preceding the use of meropenem, only 5% of patients were known to be colonized with multidrug-resistant Gram-negative pathogens. Meropenem was administered as first-line treatment in 26% of all meropenem cycles, in 74% of all FN events with meropenem, Piperacillin-Tazobactam was used for initial treatment. In 5 of 57 FN events (8.8%), initial blood cultures yielded a Gram-negative pathogen. Concerning definite treatment, appropriate alternatives to meropenem with a smaller spectrum of activity would have been available in 4 cases, but a de-escalation was not performed. The median length of therapy in the meropenem group was 6 days, the corresponding median for days of therapy (DOT) was 12 days. This corresponds with combination therapy in 56% of all meropenem treatments, mostly with teicoplanin. On average, drug dispensing data from the hospital pharmacy were 1.53 times higher than real use (relying on patients' data) without a significant correlation. A higher Case-mix Index positively correlated with meropenem-consumption. The use of meropenem should become a target of antibiotic stewardship programs in order to restrict its use to certain indications and preserve its outstanding role as second- or third-line antibiotic in this vulnerable population. Irrespective of the metrics used (g or DDD/100 inpatient days), pharmacy dispensing data do not accurately depict real patient-derived data concerning meropenem use in pediatric cancer patients.

Survey of practices for the clinical management of febrile neutropenia in children in hematology-oncology units in Latin America

The management of febrile neutropenia (FN) in pediatrics is evolving. Our objective was to describe current practices for the care of patients with FN in pediatric oncology centers in Latin America and identify areas for practice improvement. We used an online survey to enroll eligible healthcare providers who treat children with cancer in Latin America. The survey addressed respondents’ characteristics, the environment of care, and FN care practices, including risk assessment, criteria for hospitalization, initial management of FN, evaluation, antibiotic administration, and discharge. From 220 surveys sent, we received 109 responses and selected 108 from 19 countries for analysis. Most (94%) respondents were working in specialized oncology centers, oncology units within a pediatric or general care hospital. The cohort included oncologists (42%) and infectious diseases physicians (30%). Most (67%) respondents had available guidelines; they used a risk-stratification scoring system (73%) for severe infection; and their guidelines had locally adapted risk stratification (34%) or published risk stratification (51%). The respondents used diverse FN definitions and concepts, including fever definitions, temperature-obtaining methods, neutropenia values for assigning risk, empiric antimicrobials administration, and length of hospitalization. Overall, we detected common practices aligning with standard published recommendations, as well as care variability. These findings can guide further evaluations of care resources and practices to prioritize interventions, and professional networks can be used for FN discussions and consensus in Latin America.

Assessing Safe Discharge Criteria for Pediatric Oncology Patients Admitted for Febrile Neutropenia

Background: Febrile neutropenia is a common complication of myelosuppression secondary to chemotherapy. In many cases, no source of infection is found. Many pediatric oncology centers continue inpatient parenteral antibiotics therapy until myelorecovery is seen. Multiple studies suggest that outpatient therapy, oral antibiotics, or earlier discharge could be appropriate alternative treatments in some patients, supporting data are lacking. Current Children's Oncology Group guidelines recommend considering discontinuing empiric antibiotics at 72 hours in low risk patients with negative blood cultures for at least 24 hours irrespective of marrow recovery. However, this is a weak recommendation with only moderate quality evidence. With limited supporting evidence febrile neutropenia management and hospitalization duration vary by institution and individual provider.Methods: We performed a retrospective chart review of patients admitted to the Pediatric Hematology/Oncology service from September 2005 through October 2016, using ICD-9 or ICD-10 codes for “febrile neutropenia”, “neutropenia”, or “fever”, generating a list of 1555 charts. Duplicate charts, patients with fever or neutropenia but not both, and those with non-oncologic diagnoses, were eliminated, leaving 729 febrile neutropenia admissions. Of these, 131 were considered to be “early discharges” defined as discharged home at 4 or less days with discharge ANC < 500 and negative cultures. All were afebrile by the time of discharge and were released without outpatient antibiotics. These charts were then reviewed for subsequent readmission within the next 4 days.Results: 11 of the 131 patients (8%) were readmitted for reasons other than chemotherapy. 2 patients were called back from the initial admission for late positive cultures, one for Proprionibacter acnes bacterium for whom repeat cultures were negative and the second for coagulase negative staphylococcus, initially thought to be a contaminant but a second blood culture, collected prior to the initial discharge, was positive. The other 9 were readmitted with febrile neutropenia. Of these, 2 had positive cultures on readmission, 1 for pseudomonas aeruginosa and 1 for E. coli. All 4 patients with positive cultures remained stable and were safely treated with appropriate antibiotics. The remaining 7 patients had uneventful admissions and were discharged once again when afebrile with negative cultures. The mean age of the readmitted patients was younger than those not readmitted (4.2 yrs vs 7 yrs, p=0.003). The average ANC (standard deviation) at discharge was lower for the patients who were readmitted versus those not readmitted (69 (70) vs 198 (147), p=<0.001), as was APC on admission (165 (254) vs 321 (388), p=<0.001) and APC at discharge (97 (82) vs 453 (431), p=<0.001). The readmitted patients had a non-significant trend toward decline in ANC from initial admission to discharge, while those not readmitted had a slight increase in ANC (DANC -75 (211) vs +38 (209), p=0.065). Review of graphs of these values showed that use of the highest value for the readmitted patients as a cutoff would result in a large percentages of the non-readmitted patients remaining in the hospital. There was no difference with regard to gender, type of malignancy, or ANC on admission between the two cohorts.Conclusion: This retrospective review showed that low risk patients admitted with febrile neutropenia could be safely discharged prior to count recovery without oral antibiotics. Only a small percentage of patients required readmission for repeat fevers while still neutropenic, and those with bacterial infections were easily identified on readmission and appropriately treated. Not surprisingly, the readmitted group had a lower discharge ANC and APC than those not readmitted. However all patients remained stable and none suffered adverse events. Overall, 120/131 (92%) of patients deemed low risk were able to be discharged early without incident. Applying higher ANC or APC criteria for discharge would result in increased length of hospital stay for a significant population of low risk children without decreasing morbidity. [Display omitted] DisclosuresDucore:Octapharma: Research Funding; Bayer, Shire, HemaBiologics, Bioverativ, Octapharma, Spark Therapeutics: Other: Advisory board.

Epidemiology, Cytogenetic and Molecular Abnormalities and Outcome of Childhood Acute Myeloid Leukemia- an Israeli Retrospective Multicenter Study

IntroductionAcute myeloid leukemia (AML) contributes to 18% of childhood leukemia cases and about 50% of all deaths of pediatric leukemia in the United States .In high-income countries, intensive therapy has increased survival rates to 60-70% . Contributing factors to the improved survival include refinement in the diagnosis of AML and advancement in therapeutic approaches.In light of the ethnic diversity in the Israeli population, we reviewed patient's data and investigate whether the clinical, biologic and molecular features differ between Israeli Arab and Jewish AML patients.Patients and MethodsWe performed a retrospective epidemiological and clinical study including patients younger than 18 years of age, treated at all six Israeli pediatric oncology centers between 2000-2015. Down syndrome and secondary AML were excluded . The clinical characteristics such as gender, age, subtype of FAB, leukocyte count at diagnosis, cytogenetics and molecular markers were analyzed in correlation with their prognosis between different characteristics groups and different ethnicity. Survival analyses were calculated by Kaplan-Meier survival curves and the log rank test. Multivariate analyses on categorized data were performed using Cox proportional hazards model.ResultsWe analyzed 175 patients, 46% females and 54%, males, 15 % younger than 2 years old, 35% from 2 to 10 years and 50% older than 10 years (median age 9.3±5.6 years ). According to FAB subtype, the majority subtypes were M2 and M4 for 26% and 27% respectively , 40% of patients presented WBC count below 10 X 109/L at diagnosis while 13% of patients higher than 100 X 109/L. The most common cytogenetic abnormalities in these children, including t(8;21)(q22;q22), inv(16)(p13.1q22) and 11q23/MLL-rearranged abnormalities were detected, with the occurrence of 18% , 8% and 13% respectively.Acute promyelocytic leukemia (APL) was diagnosed in 14% of the children. Molecular data such as FLT3 were not evaluated due to small numbers.No statistical difference was observed regarding ethnicity as to age, white blood cell (WBC) and central nervous system (CNS) involvement. However, the Arab patients presented with a significantly higher incidence of M2 (42% vs 23% p=0.035), while the Jewish population demonstrated significantly higher incidence of M4 (33% vs. 10% p=0.011). The high incidence of M3 was common to both ethnic groups. In addition, cytogenetic subtype distribution was similar in both ethnic groups.Out of 175 patients, 114 patients were treated in accordance with the same protocol, namely BFM98 . The demographic characteristics of these 114 pts, as well as their WBC, FAB and cytogenetics were distributed similarly to the whole cohort.Among the 114 AML patients, 105 pts achieved complete remission (CR) (92%) after one course of chemotherapy. Of those who achieved CR after 2 induction cycles, 62 pts are alive and free of disease, 38 pts relapsed, 4 pts died in CR (3 due to bacterial infection and 1 due to post transplant lymphoproliferative disease) , one patient developed myelodysplastic syndrome after treatment for APL . Six patients did not go into remission after two induction phases. Three patients had early death (within six weeks of diagnosis), all due to bleeding- 2 were APL and one with MLL split and hyperleukocytosis.The median follow-up was 6.3 years (0.7y-16y), with a 5-year event free survival (EFS) and overall survival (OS) of 54% and 67% respectively.There was no prognostic significance in EFS and OS related to gender, age and ethnicity.As to risk stratification, there was a statistical difference in EFS and OS in the standard risk (SR) and the high risk (HR) group: 5 year EFS SR group 83% and 39% for HR group (p<0.0001) 5 year OS for SR group 98% and 52% for HR group (p<0.0001).ConclusionsIn this retrospective study of pediatric AML patients in Israel,the clinical, laboratory and cytogenetic characteristics were not significantly different between Jewish and Arab patients, with a similar outcome. We report a 14% incidence of APL - an incidence that is higher than that reported for the European and American populations. It may be of interest to further investigate this increased rate of APL in the Israeli population and possibly identify underlying genetic predisposing factors.The pts treated according to AML-BFM-98 protocol without pCRT have a 5y EFS and OS of 54% and 67%, respectively. These outcomes are similar to those reported for BFM98. DisclosuresNo relevant conflicts of interest to declare.

Epidemiologic and Clinical Characteristics of Clostridioides difficile Infections in Hospitalized and Outpatient Pediatric Oncology and Hematopoietic Stem Cell Transplant Patients.

The epidemiology and clinical course of Clostridioides difficile infection (CDI) in children, especially with cancer, are poorly defined. We aim to describe the epidemiology, clinical features and outcomes of CDI and to identify risk factors for recurrence in a pediatric oncology center. This is a retrospective cohort study of CDI in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients in 2016 and 2017. CDI cases were identified by positive C. difficile test in symptomatic patients. CDI episodes were classified as incident, duplicate or recurrent and community-onset, hospital-onset or community-onset healthcare facility-associated. Data about clinical course and outcomes were abstracted. Risk factors for CDI recurrence were assessed by logistic regression. One hundred seventy-eight patients 1 year of age and older developed 291 CDI episodes; 78% were incident and 22% recurrent. Underlying diagnoses were leukemia/lymphoma (57%) and solid/brain tumors (41%); 30% were HSCT recipients. Antibiotics, chemotherapy, antacids, steroids and laxatives were received by 96%, 82%, 70%, 47% and 15%, respectively. Half of the patients were neutropenic. Twenty-two percent of outpatients with CDI required hospitalization. Chemotherapy was delayed in 25%. There were no intensive care unit admissions nor deaths due to CDI. Exposure to H2-antagonists was identified as an independent risk factor for CDI recurrence. Although CDI in pediatric oncology and HSCT patients was associated with chemotherapy delay and hospitalization in approximately a quarter of patients, it was not associated with morbidity or mortality because patients had no attributable intensive care unit admission nor death. H2-antagonists are independent risk factors for CDI recurrence.

ICU Admission in Children With Acute Lymphoblastic Leukemia in Sweden: Prevalence, Outcome, and Risk Factors.

Despite progress in the treatment of childhood acute lymphoblastic leukemia, severe complications are common, and the need of supportive care is high. We explored the cumulative prevalence, clinical risk factors, and outcomes of children with acute lymphoblastic leukemia, on first-line leukemia treatment in the ICUs in Sweden. A nationwide prospective register and retrospective chart review study. Children with acute lymphoblastic leukemia were identified, and demographic and clinical data were obtained from the Swedish Childhood Cancer Registry. Data on intensive care were collected from the Swedish Intensive Care Registry. Data on patients with registered ICU admission in the Swedish Childhood Cancer Registry were supplemented through questionnaires to the pediatric oncology centers. All 637 children 0-17.9 years old with acute lymphoblastic leukemia diagnosed between June 2008 and December 2016 in Sweden were included. None. Twenty-eight percent of the children (178/637) were admitted to an ICU at least once. The Swedish Intensive Care Registry data were available for 96% of admissions (241/252). An ICU admission was associated with poor overall survival (hazard ratio, 3.25; 95% CI, 1.97-5.36; p ≤ 0.0001). ICU admissions occurred often during early treatment; 48% (85/178) were admitted to the ICU before the end of the first month of acute lymphoblastic leukemia treatment (induction therapy). Children with T-cell acute lymphoblastic leukemia or CNS leukemia had a higher risk of being admitted to the ICU in multivariable analyses, both for early admissions before the end of induction therapy and for all admissions during the study period. The need for intensive care in children with acute lymphoblastic leukemia, especially for children with T cell acute lymphoblastic leukemia and CNS leukemia, is high with most admissions occurring during early treatment.

Establishing a health economics and value unit at the Children’s Cancer Hospital–Egypt: Introducing a practical approach for evidence-based decision making.

e18859 Background: Health Economics is a multi-disciplinary practice that recently gained recognition in healthcare management systems. Value-based healthcare (VBHC) focuses on improving patient outcomes while using fewer healthcare resources. Integrating the principles of health economics and VBHC are essential to better inform decision-making based on evidence, especially in resource-limited settings, that need ultimate efficiency in managing resources. Egypt has the highest second estimated number of incident childhood cancer cases in the Eastern Mediterranean Region (EMR), based on GLOBOCAN 2020. Thus, childhood cancer in Egypt is an urging priority due to the large number of patients, limited resources, and poor outcomes. There is a need to optimize resource use and promote value in care delivery for childhood cancer care in Egypt, based on real-world evidence. Methods: This work aims to highlight the role of establishing a health economics and value (HEV) unit at the Children’s Cancer Hospital 57357 –Egypt (CCHE), to improve care and outcomes for children with cancer efficiently. CCHE is a not-for profit pediatric oncology center, treating around 50–60% of childhood cancers across Egypt free of charge. Results: The HEV unit was established in 2017 as a sub-function of the upper management at the hospital. The core mission of the unit is to translate health economics and VBHC concepts into practice to promote evidence-based decision-making, through applying the following functions and activities: monitoring trends in childhood cancer survival, resource use, and costs; applying health economic evaluation tools such as cost-effectiveness analysis (CEA) and multi-criteria decision analysis (MCDA); applying time-driven activity based costing (TDABC); implementing VBHC on a disease- and a hospital-level; monitoring costs and benchmarking. Some of these functions/activities reflect on operational processes such as integrating the CEA tools within the hospital procedures to maximize value of money spent; and restructuring hospital-wide cost centers for accurate costs reporting. Capacity building is also an important pillar in the unit’s framework, where the unit team conducts internal and external training sessions and workshops to spread the knowledge about health economics, VBHC, and evidence-based healthcare. Conclusions: The HEV unit at CCHE presents a unique model of applying health economics and value-based healthcare at a micro level in a pediatric oncology center in Egypt. This is a novel approach for healthcare management in Egypt and making informed decisions based on real-world evidence.

Evaluation of the relationship between antenatal and postnatal tobacco smoke exposure and childhood cancers.

e22011 Background: The incidence of childhood cancers increased by 1 % per year over the last three decades. Life style changes and increased variety of environmental exposures are accused of this trend. One of these environmental factors is cigarette smoking and parental smoking is the main source of tobacco smoke exposure of children. There are strong reasons for considering parental smoking behaviour as a risk factor for childhood cancers. Many tobacco related compounds are detected in fetal tissues, breast milk and tissues of children of smoking parents. However, it is hard to make causal relationship between parental smoking and childhood cancers. One of the reasons is the difficulty to detect tobacco smoke exposure. Questionnaires, commonly used method to detect tobacco smoke exposure, are prone to biases. Cotinine is the main metabolite of nicotine which is the abundant organic compound in tobacco and a good biomarker to detect tobacco smoke exposure. Methods: 104 newly diagnosed, 0-18 years aged pediatric cancer patients from two pediatric oncology centers ( Ankara University Children’s Hospital and Ankara City Hospital) and 99 healthy children aged 0-18 applied to the Ankara University Children’s Hospital participated our study. Parental smoking behaviours (preconceptional, during pregnancy and current smoking) and environmental tobacco smoke exposures (ETS) of children were compared between two groups. ETS exposures of cancer patients and healthy children were evaluated by hair cotinine ELISA analysis and questionnaire. For hair cotinine analysis, 30 mg of hair samples were taken from occipital part of scalp by a stainless scissors. Samples were processed according to manufacturer's instructions. Parents of two groups were surveyed about their smoking behaviours and ETS exposures of their children. Results: We found no differences between two groups by means of maternal preconceptional smoking, smoking during pregnancy and current smoking behaviours. Paternal preconceptional smoking and smoking during pregnancy rates were significantly low in cancer patients (p &lt; 0,05) according to questionnaire. Environmental tobacco smoke exposures were found statistically low in cancer patients according to questionnaire (p &lt; 0,05). However, quantitative exposure assessment by hair cotinine analysis revealed that cancer patients are exposed to tobacco smoke more than healthy children (p &lt; 0,001). Conclusions: Our findings support that smoking could be a risk factor for childhood cancers. This study also revealed that questionnaires could cause biases. We thought, social desirability bias of father of cancer patients could be a reason of their low smoking rates according to questionnaire. We suggest that cotinine analysis along with validated questionnaires can be used to prevent biases in studies of tobacco smoke in the etiology of childhood cancers.

Retrospective study of diffuse intrinsic pontine glioma in the Belgian population: a 25year experience.

Diffuse intrinsic pontine glioma is a rare disease with a high mortality. Our primary aim was to determine the incidence of this disease in Belgium. Secondly, we wanted to compare the treatment approach of Belgian pediatric oncology centres, to investigate possibilities for improvement. We retrospectively collected and analysed data on DIPG-patients diagnosed between 1994 and 2018 and recorded in the Belgian Cancer Registry. We included patients ≤ 18years who were followed in one of the eight Belgian pediatric oncology centres. We included 100 patients. Files were complete in 87 patients. We observed an increase in diagnoses with an incidence of 3.1 per 1,000,000 persons (aged 0-≤ 18) per year over the last 5years compared to an overall incidence of 1.8. Biopsy was performed at diagnosis in 51.7% of patients. In one fifth this was study-related. Mutation analysis was known in eight patients, of which six showed the H3 K27M-mutation. 58.8% of patients received chemotherapy, without a significant survival benefit. 12.6% of patients were included in a clinical trial. Biopsy rate and the use of chemotherapy differed widely between centres. Mean OS and PFS were 10.49 and 4.87months respectively. We observed an improved survival over time. Over the past 25years, we observed an increase of new DIPG-diagnoses. Outcome in our cohort is comparable with literature findings. We demonstrate an important heterogeneity in treatment approach between different centres and limited inclusion in clinical trials. Therefore, collaboration between centres and inclusion of patients in clinical trials is much needed.

An institutional audit of the use of novel drugs in pediatric oncology.

BackgroundSignificant challenges persist in treating children with rare, relapsed, or refractory malignancies. Novel molecularly targeted drugs promise improved outcomes for these children with reduced toxicity. However, there is often limited evidence to substantiate their clinical efficacy and guide their use. This raises issues for clinical decision‐making, ethical concerns surrounding equity of access to these often‐expensive agents, and the management of families' expectations for cure. This audit evaluated the off‐label use of novel drugs and associated clinical outcomes in order to guide the development of future clinical and ethical guidelines.AimTo evaluate the patterns in the off‐label use of novel drugs for treating childhood cancer and the associated clinical outcomes to guide prospective studies and inform ethical and clinical governance protocols for the use of these agents.MethodsA retrospective audit was performed for all patients who received novel drugs off‐label as treatment for their malignancy at an Australian pediatric oncology center between 2010 and 2019.ResultsOne hundred patients with 32 unique diagnoses received 133 novel drugs across 124 regimens. Eighty‐four patients received these drugs at the second line of treatment or greater. Novel drug median cost was $15 521 AUD (Range: $6.53 AUD to $258 339 AUD) and was primarily funded by the hospital (N = 60/133, 45.1%) or compassionate access from pharmaceutical companies (N = 52/133, 39.1%). Decision‐making related to novel drugs was inconsistently documented. Ninety‐one of 124 treatment regimens commenced between 2010 and 2019 resulted in objective responses (73.4%), but only 35 were still ongoing upon review in June 2020 (38.5%). Median response duration was 12.6 months (Range: 0‐93.2 months).ConclusionsWhile novel drugs were largely unable to definitively cure patients, most achieved objective responses. Prospective trials and more rigorous documentation are needed to fully inform the future use of these agents given the heterogeneity of their applications.

Malignant Melanoma in Children and Adolescents Treated in Pediatric Oncology Centers: An Australian and New Zealand Children's Oncology Group (ANZCHOG) Study.

ObjectivesUnlike adults, malignant melanoma in children and adolescents is rare. In adult melanoma, significant progress in understanding tumor biology and new treatments, including targeted therapies and immunotherapy have markedly improved overall survival. In sharp contrast, there is a paucity of data on the biology and clinical behavior of pediatric melanoma. We report a national case series of all pediatric and adolescent malignant melanoma presenting to ANZCHOG Childhood Cancer Centers in Australia and New Zealand.MethodsA retrospective, descriptive, multi-center study was undertaken to identify patients less than 18 years of age treated for cutaneous malignant melanoma over a twenty-year period (1994 to 2014). Data on clinical characteristics, histopathology, and extent of disease, treatment and follow-up are described.ResultsA total of 37 cases of malignant melanoma were identified from all of the Australasian tertiary Childhood Cancer Centers. The median age was 10 years (range 1 month – 17 years). Clinically, the most common type of lesion was pigmented, occurring in sixteen (57%) patients, whilst amelanotic was seen in 7 patients (25%). In 11 (27.9%) the Breslow thickness was greater than 4mm. A total of 11 (29.7%) patients relapsed and 90% of these died of disease. Five-year event free survival (EFS) and overall survival were 63.2 (95% CI: 40.6 – 79.1) and 67.7% (95% CI: 45.1 – 82.6) respectively.ConclusionOur data confirms that melanoma is a rare presentation of cancer to tertiary Australasian Childhood Cancer Centers with only 37 cases identified over two decades. Notably, melanoma managed in Childhood Cancer Centers is frequently at an advanced stage, with a high percentage of patients relapsing and the majority of these patients who relapsed died of disease. This study confirms previous clinical and prognostic information to support the early multidisciplinary management in Childhood Cancer Centers, in conjunction with expert adult melanoma centers, of this rare and challenging patient group.

Safety and Efficacy of Aminophylline in Intrathecal Methotrexate-related Neurological Toxicity in Large Pediatric Oncology Centre.

Children with acute lymphoblastic leukemia, receiving intrathecal methotrexate (IT-MTX), develop acute and subacute neurological dysfunction in 3-15% of cases. Altered level of consciousness, seizure, and stroke-like manifestations are among the most common presentations. MRI of the brain in an early stage is consistent with white matter leukoencephalopathy. There are no specific guidelines for the treatment of such a syndrome. An elevated cerebrospinal fluid (csf) adenosine concentration causes vasodilatation in the brain and leads to cerebral ischemia, which may be reduced by aminophylline infusion. The study is a retrospective data analysis in which electronic data records of 30 patients, collected from September 2017 - August 2019. The primary objective of the study was to evaluate the safety and efficacy of aminophylline in IT-MTX induced neurotoxicity. Aminophylline infusion was used in 30 patients with IT-MTX neurotoxicity. Twenty-five patients (83.33%) showed dramatic improvement of neurologic signs and symptoms within 48 hours. Aminophylline was, hence, coined as a salvageable therapy. No noticeable side effects were observed during treatment with aminophylline infusion. Key Words: Intrathecal methotrexate, Neurotoxicity, Children, Cancer, Aminophylline.