ALBERT

Description: Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and requires intensive and prolonged chemotherapy. There are limited published data describing the number and characteristics of admissions to the hospital following initial diagnosis. This study aimed to describe the number and timing of admissions in children with ALL at hospitals across the United States. Admissions were categorized as expected or unexpected to provide a more comprehensive understanding of the hospitalization patterns for children with ALL. Methods: A retrospective cohort study was designed using the Pediatric Health Information System (PHIS) database. PHIS, an administrative database that includes inpatient data from over 45 freestanding children's hospitals, contains demographic information, dates of admission and discharge, length of stay (LOS), discharge diagnosis and procedure codes, as well as billing encounters for medications. A cohort of pediatric patients with newly diagnosed ALL was previously identified using ICD-9 discharge diagnosis codes and chemotherapy exposure data. Patients were classified as high risk (HR) if billing data suggested receipt of an anthracycline within the first month of chemotherapy, otherwise patients were considered standard risk (SR). Admission patterns were explored by risk classification, age group, gender, race and ethnicity. Each admission was assessed for utilization of chemotherapy agents or parenteral antibiotics in the first two hospital days. Based on these resource utilization data admissions were hierarchically categorized as "chemotherapy related", "infection related", or "neither chemotherapy nor infection related". The former two categories were considered expected admissions while the third was considered unexpected. Each admission was also classified by the presence of billing codes for resources consistent with intensive care unit (ICU) level of care. Patient follow-up was censored at time of inpatient death or the projected end of treatment (28 months for females, 40 for males). Results: The majority of pediatric ALL patients (94.9% of HR, 87.5% of SR) had one or more admission after diagnosis. HR patients had a median of 7 admissions (range 0-43), with a 5-day median LOS (range 1-414) and median total of 55 hospitalized days (range 1-728). In contrast, SR patients had a median of 3 admissions (range 0-31), with a 4-day LOS (range 1-352) and 24 total hospitalized days (range 1-453). The distribution of admissions was skewed toward the first 6-months after diagnosis (Figure 1). Limited variability in number, duration, and timing of admissions was seen when stratifying by sex, race, or ethnicity. Of all admissions following diagnosis admission, 26.5% were chemotherapy-related, 49.1% were infection-related, and 24.3% were unexpected admissions. HR patients had a median of 1 chemotherapy-related admission (range 0-23), 3 infection-related admissions (range 0-26), and 1 unexpected admission (range 0-22). In SR patients there were 0 (range 0-21), 2 (0-20), and 1 (0-22), respectively. Children with infant leukemia (diagnosed

Description: Background: Online patient and caregiver self-reporting for symptom and toxicity monitoring during chemotherapy can inform proactive clinical management and ameliorate serious adverse events. In adults, patient-reported symptom monitoring during chemotherapy improves quality of life, decreases hospitalizations, and lengthens survival. The feasibility of this approach in pediatrics has not been established. This study assesses the implementation of daily electronic patient-reported symptom monitoring for pediatric oncology patients hospitalized for chemotherapy. Methods: The Common Terminology Criteria for Adverse Events (CTCAE) is used to grade adverse events in cancer trials. The Pediatric PRO-CTCAE is a questionnaire for children to self-report symptoms while undergoing cancer treatment. The study population was patients 7-18 years of age, English-literate, with a planned admission for chemotherapy expected to last 48 hours at a single tertiary care pediatric institution. Patients and caregivers were asked to respond daily, following text or email prompts, to Pediatric PRO-CTCAE questions addressing ten symptoms via REDCap (web-based data capture). Each morning, completed symptom reports were emailed to the frontline clinicians. No instructions were given regarding the use of patient-reported information. Utilization of symptom reports was determined by electronic survey administered to the same clinician several hours following receipt of the report. Provider acceptability was assessed monthly. Patient and caregiver satisfaction was evaluated after discharge. Results: Fifty-five patients and their caregivers were invited to participate and 45 patient/caregiver dyads enrolled (82%). Chemotherapy regimens included those for leukemia/lymphoma (40%), bone marrow transplant (BMT, 11%), solid tumor (36%) and neuro-oncology (13%). Mean patient age was 12.8 years (range 7-18). Mean length of hospitalization was 8.5 days (median 4, range 2-42). Approximately half the evaluable dyads (48.8%) generated at least one symptom report (patient or caregiver) daily; three-quarters (75.6%) submitted symptom reports at least half of all hospitalized days. When stratified to include only leukemia/lymphoma and BMT patients, mean length of stay was 13.8 days (median 6, range 2-42), and proportions of daily symptom report submissions were comparable to the overall cohort. However, all dyads with leukemia/lymphoma or BMT completed at least one symptom report following enrollment, compared to four dyads among the group with neuro-oncology or solid tumor diagnoses that submitted no symptom reports following enrollment. In response to the individual symptom reports (217 from 37 dyads) clinicians reported that clinical actions were taken 25% of the time, including counseling the use of medications already prescribed (43), prescribing a new medication or altering dosage of a currently prescribed medication (22), performing laboratory tests (1) or imaging (3), and obtaining a consult from another service or team (4). All participating healthcare providers (n=42) understood the symptom reports, and all, except one, found the reports useful and expressed interest in continuing to receive them. A quarter of providers reported that reviewing the symptom reports enhanced communication with the patient or family. Patients and caregivers found the questions easy to understand and the system easy to use. Half of the patients (51.7%) reported that submitting symptom reports helped them "a lot" or "completely" to have conversations with their doctors, and most (82.8%) expressed interest in continuing to provide symptom reports after study participation ended. Fewer caregivers (34.4%) endorsed that submitting symptom reports helped them to have conversations with the patient's doctor, but 50% noted that they helped "a lot" or "completely" to keep track of their child's health and to feel more connected to the healthcare team. Conclusion: Patient and caregiver symptom self-reporting is a feasible and acceptable strategy for symptom monitoring in pediatric patients hospitalized for chemotherapy. Patients and their caregivers find this method of symptom reporting beneficial. Further, healthcare providers find the information useful and influential in medical decision-making. Larger scale studies are needed to further assess implementation and impact of symptom monitoring. Disclosures No relevant conflicts of interest to declare.

Description: Background: CD19-targeted chimeric antigen receptor T cell therapy (CART19) has demonstrated remarkable clinical efficacy in treating relapsed/refractory B cell ALL, but associated toxicities may require treatment in inpatient or intensive care units (ICU). We sought to: (1) describe inpatient and ICU resource utilization within 30 days of CART19 infusion; and (2) evaluate trends in resource utilization from 2012-2019. Methods: We identified patients treated with CART19 on a clinical trial (NCT01626495, NCT02906371, and NCT02374333) or with the commercial product, tisagenlecleucel, at Children's Hospital of Philadelphia. Patients who received a prior cell therapy product were excluded. Demographic, pharmacy, and inpatient data were extracted from the electronic medical record from day of infusion (day 0) to day +30, censored at disease progression or death, using a semi-automated EPIC data query tool (ExtractEHR). The Virtual Pediatric Systems (VPS) database was queried for clinical data, resource utilization data, and Pediatric Risk of Mortality (PRISM) 3 and Pediatric Index of Mortality (PIM) 2 severity of illness scores. Log-binomial regression and linear regression were used to estimate the association of patient characteristics with the need for inpatient/ICU admission and inpatient/ICU length of stay (LOS), respectively. Similar models were used to estimate trends in outcomes from 2012-2019. Results: A total of 213 patients were included in the analyses. Median patient age was 12.4 years (range 1.4-29.1) at infusion; 60% were male, 66% were Caucasian, and 80% were non-Hispanic. Prior to CART19, 42% had an allogeneic hematopoietic cell transplant (alloHCT). At time of infusion, 19% had high disease burden, defined as bone marrow blasts ≥40% by flow cytometry. From 2012-2019, the proportion of patients with prior alloHCT or high disease burden decreased (Table 1). CART19 was infused in the outpatient setting in 93% of patients. In the 30 days after infusion, 70% had at least one inpatient admission, starting at a median of day +2 (IQR +1 to +6). Among the 149 patients admitted, median cumulative inpatient LOS was 7 days (IQR 4-13). Cumulative LOS increased with increasing grade of cytokine release syndrome (CRS). Median LOS was 0, 5, and 15 days for patients with no, mild, and severe CRS, respectively. From 2012-2019, there were linear trends toward decreases in proportion of patients admitted (p

Description: Background: CTL019 is a therapy derived from autologous T cells expressing a CD19-specific chimeric antigen receptor (CAR) that was approved by the FDA in August 2017 (tisagenlecleucel). Complete and durable remissions have been seen in the setting of pediatric and young adult patients with relapsed and refractory B cell acute lymphoblastic leukemia (ALL) (Maude NEJM 2018). Initial case reports suggested that there may be differential outcomes mediated by cytogenetic characteristics of the leukemia at CAR T cell infusion. Here, we report results from a single institution experience of 112 patients. Methods: Patients with relapsed/refractory ALL were identified as having received CTL019 either in the context of a clinical trial (NCT02906371) or commercial product (tisagenlecleucel) at Children's Hospital of Philadelphia from October 2016 to April 2019. Patients who received prior CAR T therapy were excluded. Demographic, cytogenetic, and outcome data were manually abstracted from the medical record or clinical trial datasets. High risk lesions were defined as MLL(KMT2A) rearrangements, Philadelphia-chromosome (Ph+), Ph-like, hypodiploidy, and TCF3/HLF fusion. Favorable cytogenetics were defined as the presence of hyperdiploidy or ETV6/RUNX1fusion and intermediate were defined as iAMP21, IKZF1deletion, or TCF3/PBX1. Patients were classified according to their highest risk cytogenetic characteristic and stratified by cytogenetic risk category present at CAR T cell infusion. Relapse-free survival (RFS) and overall survival (OS) was described for cohorts with more than 10 patients. Results: One hundred and twelve patients were included in the analysis, with a median age of 11 years (range 1-29) at infusion, of which 32% had had a previous allogeneic hematopoietic stem cell transplant (alloHSCT). Disease burden at the time of CTL019 infusion was heterogenous, with 61% having detectable disease in the bone marrow and 21% having more than 25% blasts by flow cytometry. Thirty-six patients (32%) had leukemias with high-risk genetic lesions at infusion, including 12 with MLL rearrangements and 18 with Ph+ or Ph-like lesions (Table 2). Thirty-one patients (28%) had hyperdiploidy or ETV6/RUNX1; 3 additional were in conjunction with high-risk cytogenetics (t(17;19) and 2 with Ph+), and 3 in the setting of intermediate-risk cytogenetics (iAmp21, TCF3/PBX1, IKZF1deletion). Figure 1 demonstrates RFS for those patients in remission at day 28 following infusion, stratified by cytogenetic risk category. Complete remission (CR) rate in the high-risk cytogenetics group was 94%. RFS at 12 months was 69% (0.50-0.82), 69% (0.40-0.86), and 67% (0.48-0.80) for non-informative, favorable, and high-risk cytogenetic groups, respectively. Figure 2 shows OS of patients infused with CTL019, again stratified by cytogenetic categories of interest, with a maximum follow-up time of 30 months. OS at 12 months was 84% (0.68-0.93) and 76% (0.56-0.88) for the non-informative and high-risk cytogenetic groups, respectively. There were no deaths in that time period for the favorable risk category. There was no statistically significant difference in RFS or OS for patients with high-risk cytogenetics. The intermediate-risk cytogenetics group (n