Search

Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) are at increased risk of treatment-related morbidity and mortality compared to non-DS-ALL, requiring increased supportive care. We examined the healthcare utilization and costs in DS-ALL patients to inform future evaluations of novel therapies.A provincial registry identified all children (1-17 years) diagnosed with B-lineage ALL in Ontario, Canada between 2002 and 2012. Detailed demographic, disease, treatment, and outcome data were abstracted. Linkage to population-based health services databases identified all outpatient and emergency department (ED) visits, hospitalizations, and physician billings. Healthcare utilization costs were available for patients diagnosed during 2006-2012 using validated algorithms (2018 Canadian dollars). Healthcare utilization rates and costs were compared between DS and non-DS patients using regression models, adjusting for all covariates.Of 711 patients, 28 (3.9%) had DS. Adjusting for all covariates, children with DS-ALL experienced substantially higher rates of ED visits (rate ratio [RR] 1.5, 95% confidence interval [95% CI]: 1.2-2.0; p = .001) and inpatient days (RR 2.5, 95% CI: 1.4-4.5; p = .002) compared to non-DS children. Outpatient visit rates were similar (RR 1.1, 95% CI: 0.9-1.3; p = .41). Among patients with available cost data (N = 533, DS = 19), median 5-year healthcare utilization cost was $247,700 among DS patients (interquartile range [IQR]: 200,900-354,500) and $196,200 among non-DS patients (IQR: 148,900-280,300; p = .02). In adjusted analyses, DS-associated costs were 50% higher (RR 1.5, 95% CI: 1.2-1.9; p .002).Healthcare utilization and treatment costs of DS-ALL patients are substantially higher than those of non-DS-ALL. Our data provide a baseline for future DS-specific cost-effectiveness studies.

Background Despite known clinical risk factors, predicting anthracycline cardiotoxicity remains challenging. Objectives This study sought to develop a clinical and genetic risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors. Methods We performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 case patients with reduced left ventricular ejection fraction despite low-dose doxorubicin (≤250 mg/m2), and 106 control patients with preserved left ventricular ejection fraction despite doxorubicin >250 mg/m2 were selected as extreme phenotypes. Rare/low-frequency variants were collapsed to identify genes differentially enriched for variants between case patients and control patients. The expression levels of 5 top-ranked genes were evaluated in human induced pluripotent stem cell–derived cardiomyocytes, and variant enrichment was confirmed in a replication cohort. Using random forest, a risk prediction model that included genetic and clinical predictors was developed. Results Thirty-one genes were differentially enriched for variants between case patients and control patients (p < 0.001). Only 42.6% case patients harbored a variant in these genes compared to 89.6% control patients (odds ratio: 0.09; 95% confidence interval: 0.04 to 0.17; p = 3.98 × 10–15). A risk prediction model for cardiotoxicity that included clinical and genetic factors had a higher prediction accuracy and lower misclassification rate compared to the clinical-only model. In vitro inhibition of gene-associated pathways (PI3KR2, ZNF827) provided protection from cardiotoxicity in cardiomyocytes. Conclusions Our study identified variants in cardiac injury pathway genes that protect against cardiotoxicity and informed the development of a prediction model for delayed anthracycline cardiotoxicity, and it also provided new targets in autophagy genes for the development of cardio-protective drugs. (Preventing Cardiac Sequelae in Pediatric Cancer Survivors [PCS2]; NCT01805778), Central Illustration

BACKGROUND Therapy for childhood acute lymphoblastic leukemia (ALL) is associated with substantial health care utilization and burden on families. Little is known about health care utilization during specific treatment phases. PROCEDURES We identified children with ALL diagnosed during 2002-2012 in Ontario, Canada and treated according to Children's Oncology Group (COG) protocols. Disease and treatment data were chart abstracted. Population-based health care databases identified all outpatient visits, emergency department (ED) visits, and hospitalizations. In addition to comparing standard and intensified versions of treatment phases, we compared patients receiving different steroids (dexamethasone vs. prednisone) and different versions of interim maintenance (IM) (Capizzi vs. high-dose methotrexate [HD-MTX]). RESULTS Six hundred thirty-seven children met inclusion criteria. During intensified consolidation, 76.2% of patients were hospitalized at least once, compared to only 32.3% of patients receiving standard consolidation (p

Although different treatment protocols for childhood acute lymphoblastic leukaemia (ALL) all achieve high cure rates, their health care utilisation and costs have not been rigorously compared.Disease, treatment, and outcome data were chart abstracted for all children with ALL in Ontario, Canada, diagnosed 2002-2012. Linkage to population-based databases identified health care utilisation. Utilisation-associated costs were determined through validated algorithms. Chemotherapy-associated costs were calculated separately. Health care utilisation and costs were compared between patients receiving Children's Oncology Group (COG) versus Dana-Farber Cancer Institute (DFCI)-based treatment.Of 802 patients, 146 (18.2%) were treated on DFCI-based protocols. COG patients experienced significantly higher rates of emergency department (ED) visits (adjusted rate ratio [aRR]: 1.3, 95% confidence interval [CI]: 1.1-1.5; p = 0·01), whereas outpatient visit rates were 60% higher among DFCI patients (aRR: 1.6, 95% CI: 1.5-1.7, p 0.0001). In adjusted analyses, DFCI-associated cost intensity was 70% higher (aRR: 1.7, 95% CI: 1.5-1.9; p 0.0001), mainly attributable to outpatient visit costs. Total chemotherapy costs were higher among COG-treated patients ($39,400 ± $1100 versus $33,400 ± $2800; p = 0.02). Among PEG-ASNase-treated patients, total chemotherapy costs were highest among DFCI patients (median $54,200 ± $7400; p = 0.003 versus COG patients).COG and DFCI treatments were associated with higher ED visit rates and higher outpatient visit rates, respectively. Overall utilisation-associated costs were increased in DFCI-treated patients. Administration of some intravenous chemotherapy at home and decreases in PEG-ASNase cost would decrease health care utilisation and costs for all patients and mitigate differences between COG and DFCI protocols.C

Purpose: AALL0932 evaluated two randomized maintenance interventions to optimize disease-free survival (DFS) while reducing the burden of therapy in children with newly diagnosed NCI standard-risk (SR) B-acute lymphoblastic leukemia (B-ALL). Methods: AALL0932 enrolled 9,229 patients with B-ALL; 2,364 average-risk (AR) patients were randomly assigned (2 × 2 factorial design) at the start of maintenance therapy to vincristine/dexamethasone pulses every 4 (VCR/DEX4) or every 12 (VCR/DEX12) weeks, and a starting dose of weekly oral methotrexate of 20 mg/m2 (MTX20) or 40 mg/m2 (MTX40). Results: Five-year event-free survival and overall survival (OS) from enrollment (with 95% CIs), for all eligible and evaluable SR B-ALL patients (n = 9,226), were 92.0% (91.1% and 92.8%) and 96.8% (96.2% and 97.3%), respectively. The 5-year DFS and OS from the start of maintenance for randomly assigned AR patients were 94.6% (93.3% and 95.9%) and 98.5% (97.7% and 99.2%), respectively. The 5-year DFS and OS for patients randomly assigned to receive VCR/DEX4 (n = 1,186) versus VCR/DEX12 (n = 1,178) were 94.1% (92.2% and 96.0%) and 98.3% (97.2% and 99.4%) v 95.1% (93.3% and 96.9%) and 98.6% (97.7% and 99.6%), respectively ( P = .86 and .69). The 5-year DFS and OS for AR patients randomly assigned to receive MTX20 versus MTX40 were 95.1% (93.3% and 96.8%) and 98.8% (97.9% and 99.7%) v 94.2% (92.2% and 96.1%) and 98.1% (97.0% and 99.2%), respectively ( P = .92 and .89). Conclusions: The 0NCI-SR AR B-ALL who received VCR/DEX12 had outstanding outcomes despite receiving one third of the vincristine/dexamethasone pulses previously used as standard of care on Children's Oncology Group (COG) trials. The higher starting dose of MTX of 40 mg/m2/week did not improve outcomes when compared with 20 mg/m2/week. The decreased frequency of vincristine/dexamethasone pulses has been incorporated into frontline COG B-ALL trials to decrease the burden of therapy for patients and their families.

Background: Despite known clinical and genetic risk factors, predicting anthracycline cardiotoxicity remains challenging. Objective: To develop a risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors. Methods: We performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 cases with LV ejection fraction (LVEF) ≤55% despite low-dose doxorubicin (DOX) (≤250 mg/m2), and 106 controls with LVEF >55% despite DOX >250 mg/m2 were selected as extreme phenotypes. Rare/low-frequency variants were collapsed to identify genes differentially enriched for variants between cases and controls. The top-ranked genes were functionally evaluated in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and variant enrichment was confirmed in a replication cohort. Using random forest, a risk prediction model that included genetic and clinical predictors was developed. Results: Thirty-one genes were differentially enriched for variants between cases and controls (p-15 ] suggesting that absence of these variants may predispose to cardiotoxicity. A risk prediction model for cardiotoxicity that included clinical and genetic factors had a higher prediction accuracy and lower misclassification rate compared to the clinical model. In vitro inhibition of gene-associated pathways ( PI3KR2, ZNF827 ) provided protection from cardiotoxicity in CMs. Conclusions: Our study identified variants that protect against cardiotoxicity and informed the development of a prediction model for delayed anthracycline cardiotoxicity, and also provided new targets in autophagy genes for development of cardio-protective drugs.

Sinusoidal obstruction syndrome (SOS), formerly veno-occlusive disease (VOD), in pediatric cancer patients often presents as a complication of hematopoietic stem cell transplantation, and less commonly secondary to nontransplant-associated chemotherapy. Therapy with defibrotide is well-described as standard care for transplant-associated SOS/VOD, but the treatment of nontransplant-associated SOS/VOD is less clear. We report a 3-year-old with relapsed Wilms tumor and recurrent SOS/VOD, with successful use of defibrotide during chemotherapy. A review of pediatric cancer patients with nontransplant-associated SOS/VOD treated with defibrotide revealed 83 patients, and 66 were in remission. This review supports early treatment with defibrotide in patients with nontransplant-associated SOS/VOD.

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.

7031 Background: Outcomes in pediatric acute lymphoblastic leukemia (ALL) have shown remarkable improvements in large part due to sequential clinical trials. Concerns however persist around whether access to clinical trials is equitable. It is also unclear whether patient outcomes are improved simply by enrolling on a clinical trial. Our objective was to therefore determine which patient and disease-related factors are associated with enrollment, and whether enrollment was associated with clinical outcomes among children and adolescents with ALL in a single-payer health system in Ontario, Canada. Methods: We included all Ontario patients diagnosed with ALL between 0-18 years of age from 2002-2012 treated at a pediatric center, identified through a provincial pediatric cancer registry. Clinical trial availability was determined by whether each patient’s primary institution had an open frontline trial for which the patient was eligible at the time of their diagnosis, considering individual disease characteristics such as lineage, central nervous system (CNS) status and risk group. Demographic, disease, trial enrolment, and outcome data were obtained through chart abstraction. Logistic regression models determined factors associated with trial enrolment, while Cox proportional hazard models determined factors associated with event-free and overall survival (EFS, OS). Results: Of 858 patients, 693 (81%) were eligible for an open clinical trial at their time of diagnosis. 476 (69%) enrolled on a trial. In adjusted analyses, age > 15 years (odds ratio 0.4 vs. age 5-9, 95th confidence interval (95CI) 0.2-0.8; p = 0.01) and CNS3 disease (OR 0.38 vs. CNS1, 95CI 0.17-0.83; p = 0.01) were significantly associated with decreased likelihood of enrolment, while sex and neighborhood income quintile were not associated with enrolment. Adjusted for disease and demographic factors, clinical trial enrolment was not significantly associated with either EFS (hazard ratio (HR) 1.1, 95CI 0.7-1.7; p = 0.83) or OS (HR 1.3, 95CI 0.7-2.5; p = 0.44). Conclusions: The majority of patients with ALL eligible for available clinical trials at their time of diagnosis were enrolled. While no disparities in enrolment by income status were noted, adolescents were substantially less likely to participate in trials even within pediatric centers. Studies of mechanisms underlying this disparity are warranted in order to design and implement effective interventions targeting increased enrolment rates in this patient population. Our results however also suggest that clinical trial enrolment on its own is not associated with improved outcomes in the context of a single payer health system.

Vertebral fractures (VF) are a frequent complication of acute lymphoblastic leukemia. Some children with VF undergo vertebral body reshaping to the point of complete restoration of normal vertebral dimensions. Others are left with permanent vertebral deformity if the degree of reshaping has been incomplete by the time of final adult height attainment. In this report, we describe three children with painful VF at leukemia diagnosis or during chemotherapy. Each patient highlights different clinical trajectories in their recovery from VF and underscores the need for osteoporosis intervention trials with the goal to prevent permanent vertebral deformity in selected patients.

Background An 18-month-old female toddler presented with severe vulvar ulcers and pancytopenia with investigations revealing Pseudomonas aeruginosa bacteremia. Case A previously healthy 18-month-old female toddler presented with 6 days of fevers, vulvar rash, and ulcers. Vulvar cultures showed Staphylococcus aureus and P aeruginosa. Bloodwork showed pancytopenia and P aeruginosa bacteremia. She started receiving broad-spectrum antibiotics. Bone marrow aspirate revealed a hypocellular marrow with erythroid dysplasia. Vulvar ulcers progressed rapidly, therefore magnetic resonance imaging was performed to rule out necrotizing fasciitis. She was diagnosed with ecthyma gangrenosum (EG). Three months after initial presentation, she was diagnosed with precursor B-cell acute lymphoblastic leukemia. Summary and Conclusion This case highlights that health care providers should suspect EG when severe vulvar ulcers are present with P aeruginosa infection and neutropenia. Because EG poses significant morbidity and mortality, its presence should prompt aggressive antimicrobial therapy and mobilization of a multidisciplinary team to initiate workup for an underlying immunodeficiency syndrome or malignancy. This case also illustrates that surgical debridement might be avoided in certain patients with EG as long as meticulous wound care and close monitoring with a multidisciplinary team are in place.

Providing the best care in both the inpatient and outpatient settings to pediatric oncology patients is all programs goal. Using continuous improvement methodologies, we changed from a solely team-based physician care model to a hybrid model. All patients were assigned a dedicated oncologist. There would then be 2 types of weeks of outpatient clinical service. A "Doc of the Day" week where each oncologist would have a specific day in clinic when their assigned patients would be scheduled, and then a "Doc of the Week" week where one physician would cover clinic for the week. Patient satisfaction surveys done before and 14 months after changing the model of care showed that patients were very satisfied with the care they received in both models. A questionnaire to staff 14 months after changing showed that the biggest effect was increased continuity of care, followed by more efficient clinic workflow and increased consistency of care. Staff felt it provided better planning and delivery of care. A hybrid model of care with a primary physician for each patient and assigned clinic days, alternating with weeks of single physician coverage is a feasible model of care for a medium-sized pediatric oncology program.

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.

117 Background: As childhood cancer survival approaches 85%, it is increasingly recognized that childhood cancer survivors (CCS) are at risk for long-term therapy-related complications. Data suggest that pulmonary function test (PFT) abnormalities occur in as many as 84.1% of CCS. Our aim was to assess the prevalence and nature of respiratory abnormalities in adult CCS and to correlate these abnormalities with therapeutic exposures and health behaviors. Methods: Patients who received pulmonary toxic therapy routinely undergo PFTs at their first visit to the POGO AfterCare clinic in Ottawa, Canada. We conducted a retrospective review of all patients seen in clinic from August 2015 until December 2016. PFT results, treatment exposures and health habits were documented. We used NHANES-III prediction equations for PFT interpretation, with expiratory flows and lung volumes of ≥80% predicted as cutoffs for normal. Results: Of a total of 200 patients, 48 received pulmonary toxic therapy and 38 underwent PFTs. Mean age at the time of PFT was 28.8 years (18.5-57.5 years) and the mean time from diagnosis was 17.4 years (3.4-47.5 years). Although no patients reported respiratory symptoms, 42% (16/38) demonstrated a mild restrictive ventilatory defect, 11% (4/38) had mild airflow obstruction, 18% (7/38) had an isolated reduction in diffusion capacity and 1 patient had a moderate mixed obstructive/restrictive abnormality. Only 26% (10/38) had normal lung function. Of those with restrictive defects, all received radiation and 50% were also exposed to pulmonary toxic chemotherapy. All patients with obstructive defects received radiation therapy in combination with bleomycin. Tobacco or marijuana use was reported in 26% (10/38) of the cohort, and in 29% (8/28) of those with PFT abnormalities. Conclusions: PFT abnormalities are common among adult CCS who received pulmonary toxic therapy. Studies evaluating the change in pulmonary function abnormalities over time and their correlation to cardiopulmonary exercise testing and lung imaging are required to inform the health impact on these survivors.

Myelodysplastic Syndrome (MDS) is a problem of ineffective hematopoesis, due to a clonal disorder of the hematopoetic stem cells. MDS is rare in children and considered premalignant as it often progresses to leukemia over time. There are known inherited predisposing conditions to MDS that have been reported in the literature. We describe the case of a 12-year-old girl with multiple dysmorphic features, short stature, and developmental delay with a new diagnosis of MDS (RAEB) with no confirmed genetic diagnosis linking all these features together. We propose that her underlying syndromic diagnosis may have predisposed her to MDS.

Feelings of embarrassment and fear in adolescents may contribute substantially to a delay in the diagnosis of malignant tumours arising from the genital region, with subsequent increase in morbidity and mortality. A case of a 15-year-old boy who had multiple visits to physicians with complaints of recurrent lower abdominal and back pain is presented in the current case report. He refused examination of his genital area during all visits, stating that there were no problems. The patient was admitted to the hospital with a working diagnosis of lymphoma after finding an abdominal mass and a neck mass. During bone marrow aspiration, while the patient was sedated, a large testicular mass was discovered. Each time the patient had been examined, he refused a genital examination and denied any change in the genital region.

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.