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Introduction: Though ideal models of survivorship care are not definitively established, it has been suggested that childhood acute lymphoblastic leukemia (ALL) survivors can be cared for by properly informed primary care physicians (PCP - e.g. family physicians, community pediatricians) given low risks of late effects. PCP-driven models of care are dependent on the willingness of families to re-engage with their PCPs after a prolonged period of treatment delivered by pediatric oncologists during which PCP involvement may be minimal. We thus aimed to identify rates and predictors of PCP visits both during and after treatment among a population-based cohort of children with ALL. Methods: We identified all children Results: Of 801 children with ALL, 751 (93.8%) had an identified PCP at the time of diagnosis. Excluding a further 8 (1.0%) patients who did not have treatment information available resulted in 743 cases and 3,112 controls. The median age of children with ALL was 4.0 years [interquartile range (IQR) 3.0-8.0], 409 (55%) of whom were male. Nearly half of patients (361, 48.6%) did not visit their PCP during treatment. The rate of PCP visits during treatment was 0.64 per person per year (PPPY) compared to 1.4 PPPY among controls. Adjusting for age, sex, and socioeconomic status resulted in an adjusted rate ratio (aRR) of 0.47 [95th confidence interval (95CI) 0.40-0.54; p Excluding 32 (4.3%) patients who relapsed, died, or underwent stem cell transplant prior to completing frontline therapy yielded 711 cases (survivors) and 2,973 controls available for analyses of post-treatment PCP visits. The median time of follow up after the end of treatment among survivors was 6.0 years (IQR 4.0-8.5). Though 287 (40.4%) of survivors did not visit their PCP during the post-treatment period, survivors overall still experienced greater post-treatment PCP visit rates compared to controls (aRR 1.4, 95CI 1.2-1.6; p Conclusions: Only a portion of children with ALL see their PCPs during treatment and return to PCP care following the completion of leukemia treatment, indicating that PCP-led survivorship care is feasible only for a subset of this population. The rate of PCP visits among survivors however continues to increase relative to general-population controls beyond 10 years after end of treatment. Post-treatment engagement with PCPs may be improved by PCP involvement during treatment, as well as in some cases the involvement of community pediatricians. Disclosures Gupta: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Introduction: Though cure rates for childhood acute lymphoblastic leukemia (ALL) have improved significantly, outcomes for children with relapsed ALL remain poor. Novel immunotherapies have proved effective in relapsed disease. Blinatumomab, a bispecific T-cell engager targeting CD19, was recently shown to improve disease-free and overall survival among children with high-risk relapsed disease (Brown et al, 2021) prior to proceeding to stem cell transplant. Blinatumomab however also represents a significant cost burden to institutions and healthcare systems. Our objective was thus to determine the cost-effectiveness of blinatumomab vs. standard of care therapy among children with high-risk relapsed ALL. Methods: We used a childhood ALL-specific policy simulation model previously developed using real world clinical, healthcare utilization, and cost population-based data from Ontario, Canada, and restricted it to children with B-lineage ALL who relapsed with 18 months of their original diagnosis to capture a population of patients with high-risk relapse who survived their original month of re-induction chemotherapy. This model was combined with published data from the Children's Oncology Group randomized control study AALL1331 to estimate the long-term survival, healthcare costs and quality adjusted life years associated with two courses of blinatumomab vs. two courses of standard intensive chemotherapy, followed by stem cell transplant. Combining these two sources allowed for the creation of a multi-state survival model and the estimation of the impact of blinatumomab upon relapse and survival. Healthcare costs for the administration of blinatumomab or chemotherapy were sourced from administrative data, provincial formularies, and published sources. Lifetime costs and quality-adjusted life years were calculated while Monte Carlo simulation was used to propagate parameter uncertainty in the cost-effectiveness outcomes. All costs were calculated in Canadian dollars (CAD). Results: Blinatumomab was associated with on average higher life expectancy (43.4 years vs. 36.8 years) and a higher number of quality adjust life years [2.75 QALYs gained, 95 th confidence interval (95CI) -0.44 to 5.99] but higher costs (60,420 CAD, 95CI 26,794 - 94,047) compared to standard intensive chemotherapy. The incremental cost effectiveness ratio (ICER) associated with blinatumomab was 21,970 CAD/QALY gained. However, substantial uncertainty around model parameters resulted in wide confidence intervals around cost-effectiveness outcomes. Discussion: Initial evidence indicates that the use of blinatumomab in high-risk relapse of childhood ALL as compared to standard chemotherapy is associated with a cost-effectiveness ratio that is comparable to or lower than that associated with other interventions recently introduced in pediatric ALL, and represents a cost-effective intervention for this population. However, estimates are based on limited evidence; further research is necessary to better inform several model parameters and thereby decrease uncertainty in cost-effectiveness outcomes. Disclosures Gupta: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Introduction: Children with Down Syndrome (DS) have a 20-fold increased incidence of acute lymphoblastic leukemia (ALL) and a 70% higher risk of relapse than children with ALL and no DS. Treatment for DS children with relapsed ALL is challenging due to the high treatment-related mortality associated with both intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) as well as high rates of second relapse. Outcomes for relapsed ALL in DS are dismal, with recent studies citing an event-free survival (EFS) as low as 17%. Alternative treatment approaches are needed for this patient population. Treatment with anti-CD19 chimeric antigen receptor T-cells (CARTs) have shown high remission rates in patients with multiple relapsed/refractory ALL with an acceptable safety profile. CARTs are generally not indicated for first relapse of ALL; DS-specific indications for CARTs do not exist. In Ontario, due to the specific susceptibility of children with DS-ALL, CARTs were made available to this population upon first relapse. We describe the population-based Canadian experience using CARTs for first relapse of DS-ALL. Methods: Efficacy and safety data on all children referred for CARTs at the Hospital for Sick Children, in Toronto, Canada were retrospectively collected in a central database and validated by treating clinicians. Here we report all patients with DS suffering a first relapse of ALL at age Results: Five patients with DS received tisagenlecleucel for first relapse of ALL during the study period. Median age at original diagnosis was 6.3 years (range 3.4-11.5). Four patients presenting with National Cancer Institute (NCI) standard risk and one with NCI high-risk disease were initially treated on Children's Oncology Group based protocols. Four patients presented with relapse >36 months from diagnosis and one patient with early relapse. Mononuclear cells were successfully collected for all patients on the first attempt. Patients were bridged from collection to infusion with low intensity chemotherapy regimens. Tisagenlecleucel was successfully manufactured for all patients and infused at a median of 69 days (range 56-101) from collection of T cells. Four patients developed CRS: two patients grade 1, one patient grade 2, and one patient grade 4 requiring ICU care and treatment with tocilizumab and steroid. All patients achieved minimal residual disease (MRD) negative remission one month after infusion, with B-cell aplasia. Two patients showed early (< 6months post infusion) B-cell recovery consistent with CAR T-cell loss; both received off-label reinfusions of tisagenlecleucel and again achieved B-cell aplasia. One patient had a seizure with the first Fludarabine dose of lymphodepleting (LD) chemotherapy for re-infusion and was found to have elevated intracranial pressure. After treatment with Topiramate and anti-seizure prophylaxis the patient tolerated LD chemotherapy without further neurological events. No patient received further ALL therapy; none went on to HSCT. One patient suffered a CD19-negative relapse 7 months post infusion and was transitioned to palliative-intent treatment. Two patients developed prolonged neutropenia with one patient showing recovery (ANC>1x10E9/l) at 5 months post infusion and the patient who had relapsed disease remained neutropenic until relapse. Infectious complications in the first 6 months post infusion were rare. One patient, who was not neutropenic, required two hospital admissions for line related sepsis. With a median follow-up time of 519 days (range 197-785), the 1-year estimated EFS and overall survival were both 80% (95 th confidence interval 52-100%; Figure 1). Conclusions: Tisagenlecleucel was safe and effective in a small cohort of children with DS and first relapse of CD19+ ALL, with achievement of long-term remissions without further therapy, and an EFS superior to that seen in historical cohorts. Rate of acute complications were not increased compared with reported outcomes in patients without DS. Further evaluation of tisagenlecleucel in this setting is warranted. Figure 1 Figure 1. Disclosures Krueger: KITE/Gilead: Consultancy; Novartis: Consultancy; SOBI: Consultancy. Whitlock: Sobi Pharmaceuticals: Consultancy; Novartis: Research Funding; Amgen; Jazz Pharmaceuticals: Honoraria. Gupta: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: tisagenlecleucel for early B-cell recovery

BACKGROUND: Though cooperative trial groups use different treatment protocols for newly diagnosed childhood acute lymphoblastic leukemia (ALL), all achieve high cure rates. The healthcare utilization and costs associated with different treatment strategies have not been rigorously compared. Minimizing utilization and costs may increase quality of life and decrease health system burden. We compared Children's Oncology Group (COG) and Dana-Farber Cancer Institute (DFCI)-based treatment. METHODS: We identified all children diagnosed with ALL in pediatric cancer centers in Ontario, Canada between 2002 and 2012 through the Pediatric Oncology Group of Ontario Networked Information System (POGONIS), a provincial pediatric cancer registry. Detailed data on demographics, disease risk factors (e.g. cytogenetics, minimal residual disease), treatment (e.g. treatment protocol, start and end date of each therapy phase) and events (relapse/progression, death, second cancer) were captured via chart abstraction. Treatment protocols were categorized as either based on COG or DFCI trials. Linkage to population-based health services databases identified all outpatient and emergency department (ED) visits, hospitalizations, and physician billings. Healthcare utilization-associated costs were determined through validated costing algorithms. Chemotherapy-associated costs were calculated separately using local prices. All administered doses of asparaginase (ASNase), including E. Coli, PEG-ASNase, and Erwinia ASNase were recorded. Event-free survival (EFS), overall survival (OS), healthcare utilization rates, and costs were compared between COG and DFCI-treated patients while adjusting for demographics and disease-factors using appropriate regression models. Healthcare-associated costs, ASNase costs, and total chemotherapy costs (2018 Canadian dollars) were compared. RESULTS: The study cohort included 802 patients, 146 (18.2%) of whom were treated on DFCI-based protocols. Median follow-up did not differ between between COG and DFCI patients; nor did EFS or OS. When adjusted for all demographic and disease-related variables, COG patients experienced significantly higher rates of ED visits [rate ratio (RR) 1.3, 95% confidence interval (95CI) 1.1-1.5; p=0.01]. Neither hospitalization rates nor rates of inpatient days differed between the two groups of patients. However, rates of outpatient visits were 60% higher among DFCI patients (RR 1.6, 95CI 1.5-1.7; p The median healthcare-associated cost in the first 5 years following initial diagnosis was $193,700 among COG patients [interquartile range (IQR) 149,200-272,700] compared to $288,000 among DFCI patients (IQR 233,300-407,300; p The median ASNase-related cost was similar between COG and DFCI patients [$21,100, IQR 14,800-35,400 vs. $19,900, IQR 15,600-39,900; p=0.91]. The median total chemotherapy cost was higher among COG patients ($29,100, IQR 20,300-50,300 vs. $22,400, IQR 17,300-42,600; p CONCLUSIONS: Though COG and DFCI protocols are associated with equivalent EFS and OS, patterns of healthcare utilization differ with the former associated with a 30% increase in the rate of ED visits and the latter associated with a 60% increase in the rate of outpatient visits. Overall, healthcare utilization-associated costs were increased in DFCI-treated patients. Though ASNase costs historically did not differ, the shift to PEG-ASNase is associated with higher ASNase and total chemotherapy costs on DFCI protocols. Decreases in PEG-ASNase cost and the ability to administer intravenous or intramuscular chemotherapy at home would decrease overall healthcare utilization and costs, and mitigate differences between COG and DFCI protocols. These results can inform efforts to decrease burden on both families and health systems. Disclosures No relevant conflicts of interest to declare.

Background: Chimeric antigen receptor T-cells (CAR-T) have emerged as a promising treatment for children with relapsed/refractory acute lymphoblastic leukemia (ALL). While CAR-T outcomes have been published, little data exist on how to manage these patients for the weeks to months between T-cell collection and CAR-T infusion. Unlike stem cell transplant (SCT), where higher burden of disease is associated with poor outcomes and is often a contraindication, successful outcomes for children with high disease burden pre-CAR-T have been demonstrated. Thus, traditional high-intensity chemotherapy for relapsed ALL that aims to minimize disease burden but carries significant morbidity may not be the best option for pre-CAR-T populations. We thus compared our population-based experience in using high vs. low-intensity chemotherapy regimens to bridge patients in terms of toxicity, inpatient days, and success in reaching CAR-T infusion. Methods: The Hospital for Sick Children (Sickkids) is the provincial referral centre for cellular therapy for children in Ontario, Canada. All Ontario children referred to Sickkids between 2014-2018 for first T-cell collection with intent to proceed to CAR-T therapy were included and followed until CAR-T infusion, decision to pursue alternative therapy, or death. Bridging regimen details were collected and classified as low vs. high intensity based on whether such therapy was likely associated with >7 days of neutropenia. Disease and outcome variables were compared between high vs. low intensity regimens using Chi squared, Fisher's exact, or Wilcoxon tests. Results: The cohort included 32 patients with a median age of 9.7 years at the time of first T-cell collection [interquartile range (IQR) 6.0-12.3]. The median number of previous relapses was 2 (IQR 1-2), 14 (44.0%) had undergone prior SCT, and 4 (12.5%) had Down syndrome. The vast majority of patients (28, 87.5%) were successfully bridged to receive CAR-T therapy with a median time to infusion of 81 days (IQR 60-105). Two patients experienced manufacturing failure and pursued SCT instead, 1 died of toxicity, and 1 was still awaiting infusion at the end of the study period. Low-intensity bridging regimens were used following collection for 19 (59.4%) patients, most often based on low-dose intravenous methotrexate, 3-drug induction (vincristine/steroids/asparaginase), or maintenance therapy. The most common high-intensity regimens included cyclophosphamide/etoposide, high dose cytarabine, or 4-drug induction (vincristine/steroids/asparaginase/anthracycline). Patients receiving high-intensity therapy did not seem to have more aggressive disease prior to starting bridging treatment (as indicated by peripheral blasts, number of previous relapses, prior SCT) that would have justified choosing high-intensity treatments. Patients receiving initial high-intensity regimens were however more likely to have been collected in first half of the study period (Table 1). Patients receiving initial high-intensity regimens also developed more microbiologically documented infections and experienced a greater number of inpatient days (Table 1). Excluding patients experiencing manufacturing failure or still awaiting CAR-T at the end of the study period, the likelihood of receiving CAR-T also did not vary [high-intensity regimen - 11/12 (91.7%) vs. low-intensity regimen - 17/17 (100%); p=0.41]. Conclusions: We demonstrate in our population-based cohort of heavily pre-treated and high-risk patients that initial low-intensity chemotherapy had a very high likelihood of successfully bridging children to CAR-T infusion. Low-intensity bridging regimens were associated with lower rates of toxicity and higher quality of life as indicated by fewer inpatient days. Low-intensity regimens should be considered the first line option in this population. Disclosures Grupp: Jazz Pharmaceuticals: Consultancy; Adaptimmune: Consultancy; University of Pennsylvania: Patents & Royalties; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding. Maude:Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Background: Hypothalamic-pituitary-adrenal (HPA) axis suppression is a form of adrenal insufficiency that can be found following the use of corticosteroids. Individuals with adrenal insufficiency may have non-specific symptoms or even no regular symptoms, however if presented with a physiologic stress such as infection, injury, or surgery, they are at risk of adrenal crisis. Adrenal crisis typically manifests with hypoglycemia, hypotension and critical illness; this condition is associated with significant morbidity and even mortality. Children being treated for leukemia are at increased risk of infection and may require surgical procedures, thus putting them at risk of adrenal crisis in the context of adrenal suppression. It is known that adrenal suppression exists in the short term after the induction phase of treatment in patients with acute lymphoblastic leukemia (ALL), but the prevalence and duration of suppression is still not fully understood. In addition, adrenal suppression has not been specifically evaluated during the maintenance phase of therapy. During maintenance there may be ongoing adrenal suppression from steroid use in induction, or new suppression from steroid use for maintenance therapy itself. There does not yet exist an accepted protocol to monitor for adrenal insufficiency in ALL. Knowing the prevalence and duration of adrenal suppression in maintenance will enable care teams to better recognize and manage the condition, potentially preventing significant morbidity and mortality. Methods: All cases of ALL treated at the Children's Hospital of Eastern Ontario from 2000 to 2014 were retrospectively reviewed for adrenal suppression. Patient characteristics, clinical features, laboratory data, treatment protocol utilized, adverse events and outcomes were examined. Results: 176 patients were diagnosed with new ALL at The Children's Hospital of Eastern Ontario between 2000 and 2014. Prompted by clinical suspicion, 24 had testing done to investigate for adrenal suppression during this time period. 9 of those patients had cortisol levels indicative of adrenal suppression and required further management for the same. Adrenal suppression was identified in early phases of treatment for ALL. Adrenal suppression was also identified in patients during the maintenance phase of treatment. Many more patients had symptoms that could be attributed to adrenal suppression, but never had cortisol levels tested. Conclusion: Adrenal suppression is found in children being treated for ALL, including during the maintenance phase of therapy. Adrenal suppression may have been present in greater numbers of children, but no routine testing protocol exists to identify these patients. Identifying and reviewing cases of adrenal suppression in children during treatment for ALL, including the maintenance phase, gives a better understanding of the risk of HPA axis suppression in this population. This study also provides background data for the development of a prospective study to further look at adrenal suppression in the maintenance phase of ALL. These studies will guide development of a testing protocol to better identify and manage adrenal suppression, thereby reducing its morbidity and mortality, in children being treated for ALL. Disclosures No relevant conflicts of interest to declare.

Background: Pre-B acute lymphoblastic leukemia (B-ALL) with the t(5;14) translocation occurs in less than 1% of B-ALL diagnoses. This translocation links the IGH on chromosome 14 with IL-3, which results in hypereosinophilia. Interestingly, circulating blasts or cytopenias usually don't accompany the eosinophilia. Patients often present with symptoms related to the eosinophilia, which can be quite morbid, and can delay the diagnosis of ALL. Few pediatric patients with this association have been described in the literature. The presentation and outcome can be quite variable, although it is thought that the prognosis in those patients is worse than standard ALL. Objectives: To review the laboratory and clinical features of pediatric ALL with t(5;14). Methods: Cases of pediatric patients with ALL and t(5;14) diagnosed at the Children's Hospital of Eastern Ontario between 1995 and 2003 were reviewed. Results: We present two 11 year old children, a female and a male, who were diagnosed with B-ALL with t(5;14). The first one presented with a persisting low-grade fever and weight loss as well as asymptomatic lung infiltrates on the chest xray. The second patient presented with chest pain, fever, abdominal pain, as well as a petechial rash and splinter hemorrhages. His EKG showed ST depression, his troponins were elevated and an echocardiogram showed heart dysfunction. He went on and developed behavior changes and cerebral microinfarcts. Common to their presentation was the presence of hyperoesinophilia and absence of circulating blasts. Both had aggressive disease with persistent positive minimal residual disease (MRD) after consolidation and reinduction, which sent them to stem cell transplant. Conclusion: ALL with t(5;14) is a rare entity that usually presents with hypereosinophilia. While eosinophilia can be asymptomatic, it can also be the cause of important morbidity. Diagnosis can be delayed because of the absence of blasts in the peripheral blood and lack of severe cytopenia. Finally, due to its rarity, there is very little information available on how this cytogenic abnormality impacts prognosis, which seems to be worse than ALL without this translocation. Disclosures No relevant conflicts of interest to declare.

Introduction: Providing effective outpatient care to oncology patients is the goal of all programs. There are two potential models of providing this care, a primary physician model which is the model generally employed by large oncology programs, and a team based model which is the model employed by small oncology programs. Medium sized programs (defined as 50-100 newly diagnosed patients per year), face a challenge as to what the best model of oncology outpatient care is to follow given the number of oncologists providing clinical care. We attempted to develop a hybrid model of team based and primary physician model in order to improve care of patients at our medium sized center. Methods: Prior to making any changes from the longstanding team based model of outpatient care, a patient satisfaction survey was conducted. Multiple meetings were held with the physician group to discuss the current model of care (team based model) and the potential ways to change the model given the complexity of patients and protocols. After much discussion it was decided that all patients would have a dedicated oncologist. There would then be two types of weeks of clinical service in the outpatient clinic. The first type was a “Doc of the Day” week where each oncologist would have a specific day in clinic and their assigned patients would be booked to come to clinic on those days. The second type was a “Doc of the Week” week where one physician would be attending in clinic for the week. There would be a 1:1 ratio of the two types of weeks. During vacations or holidays the week would be designated “Doc of the Week”. Results: The patient satisfaction survey done prior to changing the model of care showed that patients were very satisfied with the care they were receiving. A questionnaire to staff 14 months after the change in the model of care showed that the biggest effect was felt to be increased continuity of care to patients, followed by more efficient clinic work flow and increased consistency of care. The responses to what they liked best about the new model of care as members of the health care team, showed that facilitating the planning and delivery of care to patients and having a primary physician assigned to each patient were the most liked, followed by having their patient care questions answered more consistently because they knew which physician to direct the question to and physicians were more aware of their dedicated patients. The patient satisfaction survey post change in model of care showed that patients were still highly satisfied with the care they received. Conclusions: We showed that a model of care with a primary physician for each patient as well as assigned clinic days, alternating with some weeks where one physician covers the outpatient oncology patients for the whole week is a feasible model of care for a medium sized pediatric oncology program. The health care team found this model to be significantly better than a straight team based care model, but in a medium sized program with limited attending physicians, it provided a primary physician model that was felt to be beneficial for patients and other members of the health care team. Disclosures No relevant conflicts of interest to declare.