Purpose : Describe clinical characteristics and outcome of Li-Fraumeni-associated osteosarcomas. Methods : TP53 germline pathogenic/likely pathogenic variant carriers diagnosed with osteosarcoma in France between 1980 and 2019 were identified via the French Li-Fraumeni database at Rouen University Hospital. Sixty-five osteosarcomas in 52 patients with available clinical and histological data were included. The main clinical characteristics were compared with data from the SEER (National Cancer Institute’s Surveillance, Epidemiology, and End Results) for patients of the same age group. Results : Median age at first osteosarcoma diagnosis was 13.7 years (range:5.9-36.7). Compared to unselected osteosarcomas, LFS-associated osteosarcomas occurred more frequently in patients <10 years (23% versus 9%) and, when compared with osteosarcomas in patients <25 years were characterized by an excess of axial (16% versus 10%) and jaw sites (15% versus 3%) and histology with predominant chondroblastic component (35% versus 16%) and periosteal subtypes (17% versus 1%). Metastases incidence (25%) was as expected in unselected osteosarcomas. After the first osteosarcoma treatment, the rate of good histologic response (62%) and the 5-year progression-free survival (55%[95%CI:42.6−71.1]) were as expected in unselected series of osteosarcomas whereas the 5-year event-free survival was 36.5%[95%CI: 25.3−52.7] due to the high incidence of second malignancies reaching a 10-year cumulative risk of 55.3%[95%CI:34.3-69.5]. Conclusion : In osteosarcoma, young age at diagnosis, axial and jaw sites, histology with periosteal or chondroblastic subtype and synchronous multifocal tumors should prompt suspicion of a germline TP53 mutation. Standard treatments are effective, but multiple malignancies impair prognosis. Early recognition of these patients is crucial for tailored therapy and follow-up.

Background: Total body irradiation (TBI) is a pivotal part of conditioning prior to hematopoietic stem cell transplantation (HSCT) for childhood acute lymphoblastic leukemia (ALL), yet evidence regarding the effect of TBI delivery techniques on acute and late toxicities is sparse. Design: In a national cohort of pediatric HSCT-recipients we compared 3 TBI schedules from different time-periods: (1) TBI 12 Gray (Gy) delivered in 3 fractions from 2008-2011 (n=12), (2) 6 fractions with 2-dimensional (2D) planning technology from 2012- 2015 (n=16) and (3) 6 fractions with 3D-planning intensity-modulated radiotherapy (IMRT) from 2016-2020 (n=14). Results: The 5-year event-free survival was 75.0%, 81.3% and 81.3% in cohorts 1,2 and 3, respectively. Acute toxicity assessed as maximum ferritin and C-reactive protein during the first 3 months post-HSCT did not differ between cohorts, nor did the time to first hospital discharge (median 28, 32 and 31 days, p=0.25). The incidences of acute graft-versus-host disease (GvHD) (66%, 56%, 71%) and chronic GvHD (25%, 31% and 14%) were comparable. Pulmonary function assessed by spirometry did not differ significantly. More patients in cohort 1 developed cataract, with a 5-year cataract-free survival of 33.3%, 79% and 100% in cohorts 1,2 and 3, respectively. There was a non-significant tendency towards more endocrinopathies in cohort 1 compared to cohorts 2 and 3. Conclusion: The change of modality did not result in more relapses. More fractionation improved outcome with a lower incidence of cataract and a tendency towards fewer endocrinopathies. The effect of 3D-planning-IMRT technology requires further evaluation in larger studies.

Background: Legacy-oriented interventions have the potential to offer pediatric oncology patients and families comfort at end-of-life and during bereavement. Certified Child Life Specialists often provide these services, and presently little is known about whether disparities exist in the provision of legacy-oriented interventions. Methods: In this retrospective decedent cohort study, we examined demographic and clinical characteristics from a sample of 678 pediatric oncology patients who died between 2015-2019. Bivariate analysis assessed differences between patients who received any versus no legacy-oriented intervention. Uni- and multivariable logistic regression models assessed associations of baseline characteristics and likelihood of receiving legacy-oriented intervention. Further multivariable analysis explored joint effects of significant variables identified in the univariable analysis. Results: 52% of patients received a legacy-oriented intervention. Older adolescents (≥13 years) had lower odds (OR: 1.73, p=0.007) of receiving legacy-oriented interventions than younger ones. Patients with Home/hospice deaths showed decreased likelihood (OR: 19.98, p<0.001) compared to patients who passed away at SJCRH locations. Hispanic patients (OR: 1.53, p=0.038) and those in palliative care (OR: 10.51, p<0.001) were more likely to receive interventions. No significant race association was noted. Conclusion: All children and adolescents with cancer deserve quality care at end-of-life, including access to legacy-oriented interventions, yet nearly half of patients in this cohort did not receive these services. By identifying demographic and clinical characteristics associated with decreased odds of receiving legacy-oriented interventions, healthcare professionals can modify end-of-life care processes to improve access. Introducing legacy-oriented interventions early and increasing exposure in community spaces may enhance access to legacy-oriented interventions for pediatric oncology patients.

Objective: Vomiting is a common and distressing acute side effect of chemotherapy, negatively impacting quality of life, nutritional status and the ability of patients to tolerate further treatment. Standardized guidelines have been developed for anti-emetic regimens to improve control of nausea and vomiting. We aimed to determine the benefit of adherence to clinical practice guidelines (CPGs) on complete control of vomiting during chemotherapy in newly diagnosed pediatric patients with cancer. Methods: An electronic dashboard of pediatric patients newly diagnosed with cancer at Phoenix Children’s Hospital between August 2019 and January 2021 and receiving their first cycle of chemotherapy was utilized to monitor chemotherapy regimen, anti-emetic medications and vomiting episodes. Blocks were classified as guideline inconsistent, guideline-consistent, or guideline-consistent PLUS if additional prophylactic anti-emetic medications were utilized. We identified patients with complete control of vomiting, defined as no vomiting and no additional anti-emetics needed. Results: Among 136 patients, 29% received guideline inconsistent care, 37% received guideline-consistent care, and 34% received guideline-consistent PLUS care. 48% achieved complete control of vomiting. Older patients (p<0.0001) and higher emetogenicity chemotherapy (p=0.0003) were more likely to receive guideline-consistent or guideline-consistent PLUS therapy. With guideline-consistent and consistent-PLUS grouped together, diagnosis also was associated with improved adherence to CPGs (p=0.022). Multivariate analysis showed that patients more likely to receive guideline-consistent care were of older age (OR 1.11, p=0.016) and solid tumor patients (OR 5.59, p=0.028). Conclusions: Despite high rates of CPG adherence, complete control of vomiting remains sub-optimal which highlights the need for novel and/or risk-adapted therapies.

Title: Mixed Coagulopathy in Patient with Peroxisomal Disorder, Zellweger SyndromeAuthors: Nicholas Farris, MD1; Angela Sandell, MD2AffiliationsAssistant Professor, University of Rochester Medical Center, Division of Pediatric Hematology and Oncology, Rochester, NYAssistant Professor, University of Rochester Medical Center, Division of Gastroenterology, Rochester, NYCorresponding Author:Nicholas FarrisEmail: [email protected]: 601 Elmwood Ave, Box 777, Rochester NY, 14642Phone: 585-273-4189Fax: 575-273-1039Word Count: 462Tables, Figures, Supporting files: 0Running Title: Mixed Coagulopathy in Patient with ZellwegersKeywords: Coagulopathy, Peroxisome, Zellwegers, Intracranial Hemorrhage

Two Common Diagnostic Challenges of Juvenile Myelomonocytic LeukemiaJinjun Cheng MD PhD1,3,4*, Sarah Harney MD1, 2, David Jacobsohn MD1, 2, Reuven Schore MD1,2*Center for Cancer and Blood Disorders, Children’s National Hospital, Washington, DCDepartment of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USADivision of Pathology and Laboratory Medicine, Children’s National Hospital, Washington, DCDepartments of Pathology and Pediatrics, The George WashingtonUniversity School of Medicine and Health Sciences, Washington, District of Columbia, USA

Background: Proton therapy (PT) has potential advantages in pediatric Hodgkin lymphoma (pHL). However, there is limited data on PT, specifically to infradiaphragmatic targets. We report on PT planning details, doses achieved to organs at risk (OARs), and clinical and toxicity outcomes for patients with pHL who received PT to infradiaphragmatic regions. Methods: This is a retrospective study including patients treated between 2011-2022. Demographic and clinical factors were collected, and toxicity was reported using CTCAE version 5.0. Dosimetric and clinical factors associated with key outcomes were assessed via Cox regression. Photon plans were generated for all patients, and the paired t-test or Wilcoxon signed rank sum test were used for dosimetric comparisons. Results: Twenty-one patients comprising 22 PT courses were included. Median follow-up was 5.0 years and mean age was 14.2 years. Median dose was 21 Gray equivalent (GyE) over 14 fractions. Top acute grade 1 (G1) toxicities included fatigue (59%) and anorexia (36%). Rates of acute G2 and G3+ toxicity were 18% and 0%, respectively. After PT, no local or marginal failures occurred. 5% experienced disease progression which were all successfully salvaged, and all patients were alive and disease-free at last follow-up. No secondary malignancies developed. Compared to photon radiation, PT achieved significantly lower doses to the bowels, stomach, spleen, pancreatic tail, liver, and kidneys. Conclusions: PT is well-tolerated and leads to excellent oncologic and toxicity outcomes with long-term follow-up. PT confers dosimetric advantages when compared to photons.

Chronic myeloid leukemia (CML) is rare in children, accounting for 2-3% of pediatric leukemias. We present a case of a 10-year-old with acute appendicitis leading to the incidental discovery of CML. Due to concerns about leukostasis and tumor lysis syndrome, immediate surgical intervention was deferred in favor of medical management with antibiotics and hydroxyurea, followed by appendectomy once the leukocytosis improved. This case highlights the successful use of medical management as a bridge to surgery, providing novel insights into management of co-occurring appendicitis and CML in pediatric patients.

Pediatric secondary Chronic myelogenous leukemia in a patient with Hemophagocytic lymphohistiocytosis carrying UNC13D,LYST and ITK variantChengshuang Huang1, 2, 3 Pei Huang1, 3 Xi Luo1, 3 Zhixu He1, 3 Yan Chen1, 31Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, 563000, China2Department of Emergency Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041, PR China3Department of Pediatrics, Guizhou Children’s Hospital, Zunyi, 563000, ChinaAddress correspondence to: Yan Chen, MD, The Second Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, Guizhou, 563000, China, [email protected], +86-0851-28608293Short title: Pediatric secondary CML in a patient with HLHKeywords: Hemophagocytic lymphohistiocytosis; Secondary CML; Chemotherapy; Genetic screeningText: 839 wordsNumber of Tables: 1

Purpose: We aim to describe the characteristics of patients with childhood-onset craniopharyngioma and to analyze factors that impair quality of life (QoL) in this population. Methods: multicenter national study including patients treated between 2008-2022, from 2 to 25 years of age diagnosed with craniopharyngioma. QoL was assessed once during patient’s follow-up by age-adapted versions Pediatric Quality of Life Inventory (PedsQL TM) questionnaire. Results: Sixty-six patients were included. Median age at diagnosis was 5 years (IQR 3-8), while median follow-up was 7.4 years (IQR 2.8-9.7). Most craniopharyngioma were suprasellar (93.9%) and 59.7% had hypothalamic involvement (HI). All patients underwent surgery, 44.4% received radiotherapy and 23.6%, intra-cystic therapy. Most frequent long-term complications were visual deficit (72.7%) and endocrine impairment (94.5%). Patients exhibited hypothyroidism requiring hormone replacement (92.4%), hypocortisolism (80.3%), diabetes insipidus (86.4%) and/or growth hormone therapy (50%). When parents evaluated QoL, PedsQL TM median score was 53.8 points out of 100 (IQR 41-71.6). Higher scores were noted when patients assessed their own QoL [median-score 64.8 (IQR 57.3-81.8)], observing statistical-significant differences (p=0.019). QoL was impaired by repeated surgeries (r -0.44; p=0.014), HI [median-score 51.5 (IQR 39-63.8) vs 76.4 (59-84.8); p=0.001], radiotherapy [median-score 51.9 (IQR 38.1-61.3) vs 63.8 (IQR 49-82.5); p=0.02] and longer follow-up (r-0.3; p=0.01). Conclusion: In our study, most patients had significant comorbidities and low overall QoL scores, which was mainly affected by repeated surgery, radiation, and HI. The complex management of these patients requires multidisciplinary teams that can warrant the hypothalamic preservation and prompt intervention to prevent and identify sequelae.

In the era of big data, young patients are overwhelmed by artificial intelligence-based tools, such as chatbots. Five clinical experts were asked to evaluate the performance of four of the most currently used chatbots at providing information on a rare cancer affecting young people, such as rhabdomyosarcoma. In general, despite their high performance at giving general information about the disease, these chatbots were considered by the experts inappropriate at providing suggestion on cancer treatments and specialized centers, also lacking of "sensitivity". Efforts are envisioned by the pediatric oncology community to improve the quality of data used to train these tools.

Upfront immunotherapy for synchronous high-grade glioma and B-lymphoma in a pediatric patient with CMMRD syndrome.De Vanssay T1, El Riachy N2, Donze C1,3, Appay R2,4, Scavarda D5,6, Testud B7, Andre N1,3, Revon-Rivière G1,3Department of Pediatric Hematology, Immunology and Oncology, APHM, La Timone Children’s Hospital, Marseille, France.Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, GlioME Team, Marseille, FranceREMAP4KIDS, CNRS, INSERM, CRCM, Aix Marseille University, Marseille, France.APHM, CHU Timone, Service d’Anatomie Pathologique et de Neuropathologie, Marseille, FranceDepartment of Pediatric Neurosurgery. APHM Timone Children’s hospital. Marseille FranceAix Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, FranceDepartment of Neuroradiology, APHM, La Timone, Marseille

Background: Pediatric palliative care (PPC) is associated with improved end-of-life (EOL) outcomes. Inpatient and outpatient PPC have unique roles during the disease course. Yet, it is unknown whether the location of PPC receipt (inpatient vs outpatient) is associated with healthcare utilization and EOL outcomes for pediatric oncology patients. Procedure: A retrospective single-institution chart review of pediatric patients (age 0-28) with cancer who died between January 2015 – December 2022 was performed to compare EOL outcomes and healthcare utilization metrics among only inpatient PPC, any outpatient PPC, and non-PPC recipients. Demographics and clinical factors were analyzed by location of PPC receipt. Results: Among 450 patients, 292 (64.9%) received PPC (inpatient only (35%), any outpatient (65%)). The proportion of patients who died without receiving PPC dropped from 69% to 22% following development of an outpatient PPC clinic (p<0.001). In the last six months, one month and week of life, inpatient PPC recipients spent more days admitted to the hospital and intensive care unit (all p<0.001), and had more intensive medical interventions performed (p<0.01). Outpatient PPC recipients were less likely to receive IV chemotherapy (p<0.01) or intubation (p=0.05), and more likely to receive hospice, die at home, and have an outpatient Do-Not-Resuscitate order (all p<0.001). Conclusions: PPC receipt substantially increased after the creation of an outpatient PPC clinic, suggesting that outpatient PPC is critical in the provision of PPC to children with cancer. Outpatient PPC was associated with fewer hospital days, IV chemotherapy and intubation at EOL, while improving hospice enrollment and home death.

Treatment of Acute Lymphoblastic Leukemia is associated with neurocognitive deficits in young children. While computerized measures have been utilized in pediatric oncology research, they exclude patients below the age of 4 years old. Patients enrolled on “Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents” were offered participation in an optional cognitive study. Three-year old patients did not differ from four-year old patients on their ability to complete tests or perform tests. Including patients diagnosed at age 3 will serve to improve our understanding of at-risk patients and the cognitive trajectory of this age group both during treatment.

Background : The gift of post-mortem tissue donation is critical to pediatric CNS research. As a “Center of Excellence” for the Gift from a Child Program, our institution has a well-established post-mortem tissue donation program. Our objective was to determine if differences exist between patients that participated in and those that declined research-based autopsy. Procedure: We performed a single-institution retrospective chart review of pediatric patients with CNS malignancies who died from their disease between 1/1/2021 and 12/31/2022. Individual clinical, demographic, and socioeconomic data were assessed. Population-level data were estimated using Zip Code Tabulation Areas. Descriptive statistics were used to compare categorical data. Results : Among the 23 patient families approached during the study time frame, 8/23 (35%) consented to participation. In the consented (C) vs. declined (D) group, there was a higher percentage of White, Non-Hispanic/Latino patients by self-reported race (C: 88% vs. D: 55%) and no patients who identified as Asian or Hispanic/Latino (C: 0% & 0% vs. D: 13% & 27%). Of all patients approached, 2 required interpreters (9%) and both families declined participation. The rate of private insurance was higher in the consented group (C: 75% vs D: 47%) compared to Medicaid as primary insurance in the declined group (C: 13% vs D: 53%). Conclusions : Future research should aim to understand and improve identified disparities to ensure research advancements benefit all children with CNS malignancies. One area we plan to address is improved communication with non-English speaking families by partnering with our interpreter services.

With an annual cumulative occurrence of approximately 15,000 in North America, all childhood cancers are rare. Very rare cancers as defined by both the European Cooperative Study Group for Rare Pediatric Cancers (EXPeRT) and the Children’s Oncology Group (COG) fall into two principal categories: those so uncommon (fewer than 2 cases/million) that their study is challenging even through cooperative group efforts (e.g. pleuropulmonary blastoma, desmoplastic small round cell tumor) and those that are far more common in adults and therefore rarely studied in children (e.g. thyroid, melanoma, gastrointestinal stromal tumor). [1](#ref-0001) Treatment strategies for these latter tumors are typically based on adult guidelines, although the pediatric variants of these tumors may harbor different genetic signatures and demonstrate different behavior. If melanoma and differentiated thyroid cancer are excluded, other rare cancer types account for only 2% of the cancers in children aged 0 to 14.[1](#ref-0001) This article highlights several of the most common rare tumor types.

Background: Thrombocytopenia is a common hematologic finding in children and adolescents. Immune thrombocytopenia (ITP) is the most common cause of this finding, but the differential diagnosis includes a growing list of genetic disorders. We aimed to report differences in phenotypes of patients with ITP, inherited platelet disorder (IPD)/primary immunodeficiency disorder (PID), and other causes, with a focus on differentiating ITP from inherited thrombocytopenia. Procedure: This retrospective, population-based observational cohort from 2006 to 2020 involved 506 Finnish children under 16 years of age presenting with isolated thrombocytopenia. Results: Of the 506 participants, 79.7% had ITP, 6.7% had IPD/PID, and 13.6% had other causes of thrombocytopenia. A platelet count of ≤12 × 10 9/l best distinguished between ITP and other reasons with a sensitivity of 60% and a specificity of 80%. Among patients with the lowest platelet count of <10 × 10 9/l, 95.9% had ITP, 3.3% had IPD/PID, and 0.8% had other causes. Severe bleeding events were reported in 20 patients (4.0%), but there were no cases of intracranial or fatal bleeding due to thrombocytopenia. Up to 50% of patients with a high suspicion of inherited thrombocytopenia remained without a specific diagnosis despite genetic testing. Conclusions: ITP remains the most common cause of thrombocytopenia. A platelet count of ≤12 × 10 9/l often leads to an ITP diagnosis. Genetic disorders are rare but should be suspected in patients with persisting thrombocytopenia, especially with platelet counts constantly above 12 × 10 9/l, a positive family history, or atypical clinical features.

IntroductionTAM is characterized by a transient proliferation of abnormal myeloid cells in the bone marrow, leading to an excess of immature cells circulating in the peripheral blood [2]. TAM diagnosis is associated with the presence of GATA1 mutations, but other features such as blasts on peripheral blood smear, flow cytometry immunophenotype or cytogenetics can be indicative of TAM. This patient’s case is unusual due to the GATA1 mutation-negative status. The GATA1 gene encodes a transcription factor crucial for normal hematopoiesis and mutations in this gene are associated with myeloid disorders including TAM [3]. TAM leads to a wide range of hematologic abnormalities and clinical complications including hyperviscosity syndrome with potential for thrombosis, hydrops fetalis, pericardial effusion, respiratory distress, hypereosinophilia, pseudohyperkalemia, hyperbilirubinemia with liver failure, multi-organ failure and potential for death [1,2,5,14]. Patients with TAM require timely diagnosis as well as close follow up, as 20-30% of these patients subsequently develop myeloid leukemia associated with Down Syndrome (ML-DS) before the age of four [4]. GATA1 mutations have, to date, been discovered in nearly all patients with TAM and ML–DS [7]. The absence of aGATA1 mutation in this case raises the question of an alternative molecular mechanism contributing to the development of TAM and extreme thrombocytosis in this patient.