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Background: Oral chemotherapy nonadherence is a challenge in clinical oncology. During therapy for acute lymphoblastic leukemia (ALL), poor adherence to 6-mercaptopurine (6MP) increases relapse risk. Clinically significant nonadherence is reported in 30% of children treated for ALL on Children's Oncology Group (COG) trials. Whether nonadherence rates vary across regimens with different treatment schedules and modes of administration is unknown. Methods: We conducted an exploratory, cross-sectional survey study on parents of children (1–18 years) receiving continuation therapy on, or as per Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 11-001. Treatment required weekly visits to the clinic and 14 days of oral 6MP every 3 weeks. Survey assessed self-reported sociodemographics, medication-taking, chemotherapy comprehension, and 6MP adherence; adherence survey items were developed from published surveys. Patients were grouped as nonadherent if they endorsed missing one 6MP dose during the last cycle, or more than one dose during prior cycles, for nonmedical reasons. Results: Sixty-two families completed the surveys, all of whom had evaluable adherence data. In total, 25% of patients met the study definition of nonadherence. Twenty-three percent reported that it was “not easy” to follow administration guidelines around the dairy intake and 57% requested more teaching and educational resources. Conclusion: Self-reported nonadherence to oral 6MP in the DFCI ALL Consortium is high, with rates similar to those observed in the COG. This suggests that the additional contact during weekly infusions on the DFCI is insufficient to address barriers affecting oral chemotherapy adherence.

Background: We examined the impact of race/ethnicity and age on survival in a publicly insured cohort of children and adolescent/young adults (AYA; 15–39 years) with Hodgkin lymphoma, adjusting for...

VAF concordance

Supplementary Data file including supplementary methods and clinical case vignettes.

Reasons for not using recommended targeted therapy.

Patient sequencing data, by patient number and diagnosis.

PURPOSEImplementation of routine financial screening is a critical step toward mitigating financial toxicity. We evaluated the feasibility, sustainability, and acceptability of systematic financial screening in the outpatient breast oncology clinic at a large, urban cancer center.METHODSWe developed and implemented a stakeholder-informed process to systematically screen for financial hardship and worry. A 2-item assessment in English or Spanish was administered to patients through the electronic medical record portal or using paper forms. We evaluated completion rates and mode of completion. Through feedback from patients, clinicians, and staff, we identified strategies to improve completion rates and acceptability.RESULTSFrom March, 2021, to February, 2022, 3,500 patients were seen in the breast oncology clinic. Of them, 39% (n = 1,349) responded to the screening items, either by paper or portal, 12% (n = 437) preferred not to answer, and the remaining 49% (n = 1,714) did not have data in their electronic health record, meaning they were not offered screening or did not complete the paper forms. Young adults (18-39 years) were more likely to respond compared with patients 70 years or older (61% v 30%, P < .01). English-preferring patients were more likely to complete the screening compared with those who preferred Spanish (46% v 28%, P < .01). Non-Hispanic White patients were more likely to respond compared with Non-Hispanic Black patients and with Hispanic patients (46% v 39% v 32%, P < .01). Strategies to improve completion rates included partnering with staff to facilitate paper form administration, optimizing patient engagement with the portal, and clearly communicating the purpose of the screening.CONCLUSIONSystematic financial screening is feasible, and electronic data capture facilitates successful implementation. However, inclusive procedures that address language and technology preferences are needed to optimize screening.

Adolescents and young adults (AYA) with sarcoma experience both acute and chronic pain related to their disease and treatment. Studies in older adults have reported a high risk of persistent opioid use after cancer therapy among previously opioid-naive patients; however, few studies have evaluated posttreatment opioid use among AYAs. This article describes patterns of new persistent opioid use among AYAs in the year after treatment for sarcoma.Opioid-naive patients who were 10 to 26 years old and diagnosed with sarcoma (2008-2016) were identified with the IBM Marketscan Database. Included subjects had an International Classification of Diseases code for sarcoma (ninth or tenth revision), received anticancer therapy (chemotherapy, surgery, and/or radiation) within 30 days of the first diagnosis code, and had continuous insurance coverage (commercial or Medicaid) for more than 12 months both before the diagnosis and after the last therapy. The primary outcome was new persistent opioid use, which was defined as at least 2 opioid prescriptions in the 12 months following treatment completion. Covariates included age, sex, insurance, tumor type, surgical procedure, mental health (MH) or substance use diagnoses before or during therapy, and concomitant lorazepam use.In total, 938 patients met the inclusion criteria; 521 (56%) were male, and 578 (62%) were younger than 18 years. In total, 727 (78%) had commercial insurance, and 273 (29%) had an MH diagnosis either before or during the treatment period. Of the total group, 464 (49%) used opioids during treatment only. Of those who used opioids during treatment, 135 (23%) received at least 2 prescriptions in the year after therapy. In a multivariable analysis, Medicaid versus commercial insurance (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.15-2.64) and non-soft tissue sarcoma (OR for Ewing sarcoma, 3.23; 95% CI, 1.81-5.78; OR for osteosarcoma, 2.05; 95% CI, 1.36-3.09) conferred a higher likelihood of new persistent use.In this cohort of AYAs treated for sarcoma, 64% of the patients received opioid prescriptions during treatment, and 23% of these patients became new persistent users. Because of the risks associated with persistent opioid use, studies of novel pain management strategies along with age-appropriate education and anticipatory guidance are urgently needed.Using an insurance claims database, we conducted a study to determine the rate of new persistent opioid use among adolescents and young adults treated for sarcoma. We found that 64% of adolescents and young adults treated for sarcoma received opioid prescriptions during treatment, and 23% of these patients met the criteria for new persistent opioid use. These findings support the need for age-appropriate education and novel pain management strategies in this vulnerable population.

Adolescents and young adults (AYAs; age 15-39 years) with cancer are under-represented in cancer clinical trials because of patient, provider, and institutional barriers. Health care technology is increasingly available to and highly used among AYAs and has the potential to improve cancer care delivery. The COVID-19 pandemic forced institutions to rapidly adopt novel approaches for enrollment and monitoring of patients on cancer clinical trials, many of which have the potential for improving AYA trial participation overall. This consensus statement from the Children's Oncology Group AYA Oncology Discipline Committee reviews opportunities to use technology to optimize AYA trial enrollment and study conduct, as well as considerations for widespread implementation of these practices. The use of remote patient eligibility screening, electronic informed consent, virtual tumor boards, remote study visits, and remote patient monitoring are recommended to increase AYA access to trials and decrease the burden of participation. Widespread adoption of these strategies will require new policies focusing on reimbursement for telehealth, license portability, facile communication between electronic health record systems and advanced safeguards to maintain patient privacy and security. Studies are needed to determine optimal approaches to further incorporate technology at every stage of the clinical trial process, from enrollment through study completion.

We compared secondary primary malignancy risk (SPM) in HIV-uninfected and HIV-infected Hodgkin lymphoma (HL) survivors. We used data from the California Cancer Registry on patients diagnosed with HL from 1990 to 2015 (all ages included), and standardized incidence ratios (SIRs) and multivariable competing risk models for analyses. Of 19,667 survivors, 735 were HIV-infected. Compared with the general population, the risk of SPM was increased by 2.66-fold in HIV-infected and 1.92-fold in HIV-uninfected survivors. Among HIV-infected survivors, median time to development of SPM was shorter (5.4 years) than in HIV-uninfected patients (8.1 years). Additionally, the highest risk of SPM was observed

Adolescents with Hodgkin lymphoma have worse disease outcomes than children. Whether these differences persist within clinical trials is unknown. We examined survival, by age, in patients receiving response-adapted therapy for Hodgkin lymphoma on Children's Oncology Group (COG) trials.Patients (aged 1-21 years) diagnosed with classical Hodgkin lymphoma and enrolled between Sept 23, 2002, and Jan 19, 2012, on one of three phase 3 COG trials in the USA and Canada were eligible for inclusion. The three COG trials were defined by risk group according to Ann Arbor stage, B-symptoms, and bulk (AHOD0431 [low risk; NCT00302003], AHOD0031 [intermediate risk; NCT00025259], or AHOD0831 [high risk; NCT01026220]). The outcomes of this study were event-free survival (death, relapse, or subsequent neoplasm) and overall survival. Cox proportional hazards models estimated survival, adjusting for disease and treatment factors both overall and in patients with mixed cellularity or non-mixed cellularity (nodular sclerosing and not-otherwise-specified) disease.Of 2155 patients enrolled on the three trials, 1907 (88·4%; 968 [50·8%] male and 939 [49·2%] female; 1227 [64·3%] non-Hispanic White) were included in this analysis. After a median follow-up of 7·4 years (IQR 4·3-10·2), older patients (aged ≥15 years) had worse unadjusted 5-year event-free survival (80% [95% CI 78-83]) than did younger patients (aged15 years; 86% [83-88]; HR 1·38 [1·11-1·71]; p=0·0038). Older patients also had worse unadjusted 5-year overall survival than did younger patients (96% [95% CI 95-97] vs 99% [98-99]; HR 2·50 [1·41-4·45]; p=0·0012). In patients with non-mixed cellularity histology, older patients had a significantly increased risk of having an event than did younger patients with the same histology (HR 1·32 [1·03-1·68]; p=0·027). Older patients with mixed cellularity had significantly worse 5-year event-free survival than did younger patients in unadjusted (77% [95% CI 65-86] for older patients vs 94% [88-97] for younger patients; HR 2·93 [1·37-6·29]; p=0·0039) and multivariable models (HR 3·72 [1·56-8·91]; p=0·0032). Overall, older patients were more likely to die than younger patients (HR 3·08 [1·49-6·39]; p=0·0025).Adolescents (≥15 years) treated on COG Hodgkin lymphoma trials had worse event-free survival and increased risk of death compared with children (15 years). Our findings highlight the need for prospective studies to examine tumour and host biology, and to test novel therapies across the age spectrum.National Institutes of Health, St Baldrick's Foundation, and Lymphoma Research Foundation.

Background Both adolescent and young adult (AYA) and Black or African American (hereafter referred to as Black) cancer patients are historically under‐enrolled in cancer treatment trials (CTT). The purpose of this study was to quantify enrollment of Black AYAs in National Cancer Institute (NCI)‐sponsored CTTs overall and by age, sex, and cancer diagnosis during 2000–2015. Methods Utilizing data from NCI’s Cancer Therapy Evaluation Program and the Surveillance, Epidemiology and End Results (SEER) Program, we assessed CTT enrollment in Black patients with cancer and measured changes in enrollment over time between the study periods 2000–2007 and 2008–2015. Enrollment patterns were compared across age groups (≤14 years [y], 15–19y, 20–29y, 30–39y and 40+ years), sex, and cancer diagnosis. Results From 2000 through 2015, This study documents that compared with Black children, Black adolescent and young adult (AYA) patients were less likely to enroll in NCI‐sponsored CTTs from 2000 to 2015. Black AYA male enrollment decreased with increasing age, highlighting disparities among this specific population in CTT enrollment.

BackgroundHodgkin lymphoma (HL) is a treatable tumor affecting children, adolescents and young adults (AYAs; 15-39 years old). Population-based studies report worse survival for non-White children and AYAs but have limited data on individual therapeutic exposures. This study examined overall and HL-specific survival in a population-based cohort of patients while adjusting for sociodemographic factors and treatment.MethodsData for 4807 patients younger than 40 years with HL (2007-2017) were obtained from the California Cancer Registry. Individual treatment information was extracted from text fields; chemotherapy regimens were defined by standard approaches for pediatric and adult HL. Multivariable Cox models examined the influence of patient and treatment factors on survival.ResultsAt a median follow-up of 4.4 years, 95% of the patients were alive. Chemotherapy differed by age, with 70% of 22- to 39-year-olds and 41% of

Social determinants of health (SDoH) are associated with stark disparities in cancer outcomes, but systematic SDoH data collection is virtually absent from oncology clinical trials. Trial-based SDoH data are essential to ensure representation of marginalized populations, contextualize outcome disparities, and identify health-equity intervention opportunities. We report the feasibility of a pediatric oncology multicenter therapeutic trial-embedded SDoH investigation. Among 448 trial participants, 392 (87.5%) opted-in to the embedded SDoH study; 375 (95.7%) completed baseline surveys, with high longitudinal response rates (88.9-93.1%) over 24 months. Trial-embedded SDoH data collection is feasible and acceptable and must be consistently included within future oncology trials.

Hispanic children have a higher incidence of acute lymphoblastic leukemia (ALL) and inferior treatment outcomes relative to non-Hispanic White children. We previously reported that Hispanic children with ALL had lower risk of fracture and osteonecrosis. To unravel the genetic root of such ethnic differences, we genotyped 449 patients from the DFCI 05-001 cohort and analyzed their ancestry. Patients with discordant clinical and genetic ancestral groups were reclassified, and those with unknown ancestry were reassigned on the basis of genetic estimates. Both clinical and genetic ancestries were analyzed in relation to risk of bone toxicities and survival outcomes. Consistent with clinically reported race/ethnicity, genetically defined Hispanic and Black patients had significantly lower risk of fracture (Hispanic: subdistribution hazard ratio [SHR], 0.42; 95% confidence interval [CI], 0.22-0.81; P = .01; Black: SHR, 0.28; 95% CI, 0.10-0.75; P = .01), and osteonecrosis (Hispanic: SHR, 0.12; 95% CI, 0.02-0.93; P = .04; Black: SHR, 0.24; 95% CI, 0.08-0.78; P = .02). The lower risk was driven by African but not Native American or Asian ancestry. In addition, patients with a higher percentage of Native American ancestry had significantly poorer overall survival and event-free survival. Our study revealed that the lower risk of bone toxicities among Black and Hispanic children treated for ALL was attributed, in part, to the percentage of African ancestry in their genetic admixture. The findings provide suggestive evidence for the protective effects of genetic factors associated with African decent against bone damage caused by ALL treatment and clues for future studies to identify underlying biological mechanisms.

The advances in pediatric cancer outcomes over the last quarter century are some of the most successful in modern medicine. Improved diagnostics and novel therapies have led to continued increases in the survival rates of most patients; however, not all populations have benefitted equally. Compared to White children, Black, Indigenous, People of Color patients with cancer more often present with advanced stage illness, less frequently participate in clinical trials, and are more likely to be lost to follow-up once therapy is complete. Proposed hypotheses for these disparities include both biologic and nonbiologic factors, and a growing body of research suggests that barriers influencing care from diagnosis through survivorship are important. In this article, we consider how primary pediatricians can help reduce disparities over the cancer continuum by identifying vulnerable populations, considering potential diagnoses, referring to cancer centers, and following up with patients through survivorship in partnership with the oncology team. [ Pediatr Ann . 2022;51(1):e22–e26.]

Background Food insecurity (FI) is an adverse social determinant of health (SDoH) prevalent among pediatric cancer patients and associated with poorer health outcomes in general pediatrics. Receipt of federal SNAP benefits reduces FI in general pediatrics, and is thus a marker of appropriate resource support to mitigate adverse SDoH. Dana-Farber Cancer Institute (DFCI) Acute Lymphoblastic Leukemia (ALL) Consortium Trial 16-001 is the first pediatric oncology clinical trial to prospectively collect parent-reported SDoH, including income, SNAP receipt, and FI. We investigated whether income-eligible pediatric ALL families were successfully receiving SNAP benefits, and whether SNAP receipt was associated with FI. Methods Secondary analysis of children aged 1-17 years with de novo ALL enrolled on the DFCI 16-001-embedded SDoH cohort study at 6 US centers from 2017-2022. We utilized parent-reported SDoH data at diagnosis (T0) and 6-mos (T1) into therapy to identify families as (1) SNAP-eligible, proxied as household income Citation Format: Rahela Aziz-Bose, Yael Flamand, Puja J. Umaretiya, Lenka Ilcisin, Ariana Valenzuela, Peter D. Cole, Lisa M. Gennarini, Justine M. Kahn, Kara M. Kelly, Bruno Michon, Thai-Hoa Tran, Jennifer J. G. Welch, Lewis B. Silverman, Kira Bona. Food insecurity and receipt of Supplemental Nutrition Assistance Program (SNAP) benefits among income-eligible US pediatric acute lymphoblastic leukemia patients enrolled on a multi-center clinical trial [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B096.

The molecular hallmark of childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent, prognostic genetic alterations, many of which are cryptic by conventional cytogenetics. RNA sequencing (RNA-seq) is a powerful next-generation sequencing technology that can simultaneously identify cryptic gene rearrangements, sequence mutations and gene expression profiles in a single assay. We examined the feasibility and utility of incorporating RNA-seq into a prospective multicenter phase 3 clinical trial for children with newly diagnosed ALL. The Dana-Farber Cancer Institute ALL Consortium Protocol 16-001 enrolled 173 patients with ALL who consented to optional studies and had samples available for RNA-seq. RNA-seq identified at least 1 alteration in 157 patients (91%). Fusion detection was 100% concordant with results obtained from conventional cytogenetic analyses. An additional 56 gene fusions were identified by RNA-seq, many of which confer prognostic or therapeutic significance. Gene expression profiling enabled further molecular classification into the following B-cell ALL (B-ALL) subgroups: high hyperdiploid (n = 36), ETV6-RUNX1/-like (n = 31), TCF3-PBX1 (n = 7), KMT2A-rearranged (KMT2A-R; n = 5), intrachromosomal amplification of chromosome 21 (iAMP21) (n = 1), hypodiploid (n = 1), Philadelphia chromosome (Ph)-positive/Ph-like (n = 16), DUX4-R (n = 11), PAX5 alterations (PAX5 alt; n = 11), PAX5 P80R (n = 1), ZNF384-R (n = 4), NUTM1-R (n = 1), MEF2D-R (n = 1), and others (n = 10). RNA-seq identified 141 nonsynonymous mutations in 93 patients (54%); the most frequent were RAS-MAPK pathway mutations. Among 79 patients with both low-density array and RNA-seq data for the Philadelphia chromosome-like gene signature prediction, results were concordant in 74 patients (94%). In conclusion, RNA-seq identified several clinically relevant genetic alterations not detected by conventional methods, which supports the integration of this technology into front-line pediatric ALL trials. This trial was registered at www.clinicaltrials.gov as #NCT03020030.

Burkitt lymphoma is a highly aggressive type of non-Hodgkin lymphoma (NHL), often requiring intense inpatient chemotherapy and supportive care [1]. While pediatric, adolescent and young adult (YA) ...

Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence Tier 1 or 2 recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance, performed ex vivo drug-sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials. Significance: Patients with relapsed/refractory leukemias face limited treatment options. Systematic integration of precision medicine efforts can inform therapy. We report the feasibility of identifying targetable mutations in children with leukemia and describe correlative biology studies validating therapeutic hypotheses and novel mutations. See related commentary by Bornhauser and Bourquin, p. 1322. This article is highlighted in the In This Issue feature, p. 1307

Introduction Second primary malignancy (SPM) is one of the most devastating late complications following Hodgkin lymphoma (HL) treatment. Historically, the most common SPMs in patients treated for HL are solid tumors, which are largely related to radiation exposure during initial therapy. For the last three decades, efforts to address the risk of SPM after HL therapy have focused on reducing exposure to radiation, as well as refining the approach for patients where radiation is indicated. To date, few population-based studies in the United States have quantified the burden of SPMs and evaluated the potential effect of changes in therapeutic management over time. Additionally, to our knowledge, no study has compared SPM risk between human immunodeficiency virus (HIV)-infected and HIV-uninfected HL survivors. Methods We used data from the California Cancer Registry on 21,043 patients diagnosed with primary HL between 1988 and 2015 with follow-up through 2017. We calculated standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs) and absolute excess risks (AERs) to compare SPM incidence in our HL cohort with the expected number of first primary cancer incidence in the general California population, based on patient's age at diagnosis (5-year categories), sex, calendar year (3-year intervals), cancer site, and race/ethnicity. SIRs are presented by HIV status, SPM latency, treatment era, and cancer type. P-values for trends were used to examine whether SPM risk changed over time. Findings Among 20,303 HIV-uninfected patients (median follow-up of 14.1 years), overall SPM risk was increased 1.95-fold compared with the general population (SIR=1.95, 95% CI 1.86-2.04). In 740 HIV-infected patients (median follow-up of 11.7 years), overall risk was increased 2.68-fold compared with the general population (SIR=2.68, 95% CI 2.0-3.40), translating to an 37% higher incidence of SPM in HIV-infected vs. HIV-uninfected patients. The AER (per 10,000 person-years) of SPM was 43.1 in HIV-uninfected and 76.5 in HIV-infected patients, resulting in a 33.4 excess SPM per 10,000 person-years in HL survivors with HIV. Malignancies that contributed the most to overall AER were non-Hodgkin lymphoma (NHL), female breast and lung cancers in HIV-uninfected patients; and Kaposi sarcoma, NHL, anorectal and head & neck (HNC) cancers in HIV-infected patients. Notably, among HIV-uninfected patients, the highest overall risk of SPM occurred ≥20 years after diagnosis (SIR= 2.27, 95% CI 1.99-2.58) (Figure). In contrast, the highest overall risk in HIV-infected patients was observed Conclusion Compared with the general population, the risk of developing a SPM following HL treatment was significantly higher among both HIV-uninfected and HIV-infected patients, with the absolute excess risk greater for those with HIV infection. There were different temporal patterns and types of SPM between HIV-uninfected and HIV-infected patients. These findings prompt the question on whether earlier and/or more intensive cancer screening should be pursued for HIV-infected survivors. The trend towards decreased risk for selected solid SPMs among HIV-uninfected patients, especially lung and female breast cancers, suggest that strategies to reduce radiation in HL survivors may be working. Despite promising trends in this group, the observation that SPM risk was highest ≥20 years after initial therapy further highlights the need for long-term surveillance and survivorship care in this at-risk population. Disclosures Rosenberg: Takeda: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Wun:Glycomimetics, Inc.: Consultancy.

Introduction: Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening condition associated with endothelial cell damage due to hematopoiet...

Vincristine, a key agent in the treatment of many pediatric malignancies, causes sensory, motor and autonomic neuropathy. We report the clinical courses of 5 patients who required cessation of vincristine after developing severe neurotoxicity during treatment for acute lymphoblastic leukemia. All 5 patients lost the ability to ambulate and 3 had additional severe neurotoxic side effects including vision loss and vocal cord dysfunction. Although prior literature reports poor outcomes for children in whom vincristine was discontinued during acute lymphoblastic leukemia therapy, all 5 patients described here achieved and have maintained complete continuous remission.

Despite extraordinary strides in cancer therapy over the past 30 years, racial/ethnic, socioeconomic, and age-related survival disparities persist. Hodgkin lymphoma offers an excellent paradigm to understand these disparities because successful approaches are well established in both the up-front and relapsed treatment settings. The following review, which accompanies the 2021 NCCN Guidelines for Pediatric Hodgkin Lymphoma, suggests that systemic inequities in cancer care disproportionately affect minority and low-income children, adolescents, and young adults, and directly contribute to observed disparities in cancer-related outcomes. It proposes that the first step toward reducing disparities is large-scale dissemination of guidelines, because equity is best achieved when treatment approaches are clear, comprehensive, and standardized across all clinical practice settings.

Poor adherence to 6-mercaptopurine during acute lymphoblastic leukemia (ALL) therapy increases relapse risk. Clinically-significant non-adherence has been documented in up to 30% of children treated for ALL on Children’s Oncology Group trials. Whether non-adherence rates vary across regimens with different chemotherapy schedules and modes of administration is not known. In a cross-sectional survey study of N= 61 children treated on, or as per Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 11-001, 25% (95% CI 14 – 37%) of respondents self-reported non-adherence to 6MP, suggesting that the frequency of non-adherence may be similar across different Consortia regimens.

Identifying which patients are at high risk for transplant-related mortality, prior to allogeneic hematopoietic cell transplantation (alloHCT), is crucial both to guide decision making with patients and families and to inform the alloHCT approach. There is a paucity of data evaluating the utility of the HCT comorbidity index (HCT-CI) in pediatric patients. We performed a retrospective cohort study of 188 patients who underwent alloHCT between January 2008 and October 2016 and assessed pretransplant comorbidities defined and weighted by the HCT-CI. The primary endpoint of our study was overall survival (OS). Kaplan-Meier method was used to assess survival estimates at 1-year post-transplant and did not differ based on HCT-CI scores: 78.7% (SE 6.69%) for HCT-CI = 0, 74.7% (SE 6.33%) for HCT-CI = 1 to 2, and 77.3% (SE 4.17%) for HCT-CI ≥3. Multivariable Cox proportional hazards analysis did not show HCT-CI having an effect on OS: hazard ratio (HR) of 0.633 (95% confidence interval [CI], 0.297 to 1.347) for HCT-CI scores 1 to 2 and HR of 0.935 (95% CI, 0.456 to 1.918) for HCT-CI scores ≥3 compared to scores of 0. The most frequent comorbidities observed were hepatic disease (mild in 29%, severe in 23%) and pulmonary disease (moderate in 15% and severe in 29%). However, only 55% were able to complete pulmonary function testing. Hepatic disease was based on transaminitis in 48% and by bilirubin alone in 26% of patients; 46% of patients with hepatic dysfunction had an underlying hemoglobinopathy and hyperbilirubinemia related to ongoing hemolysis. This study evaluates HCT-CI comorbidities in greater detail than has been performed previously in children undergoing alloHCT. We identify challenges with the HCT-CI in the pediatric population and highlight the comorbidities that may benefit from adjustments to their definition to create an improved risk assessment tool for children.

BACKGROUND/OBJECTIVES While outcomes for pediatric T-cell acute lymphoblastic leukemia (T-ALL) are favorable, there are few widely accepted prognostic factors, limiting the ability to risk stratify therapy. DESIGN/METHODS Dana-Farber Cancer Institute (DFCI) Protocols 05-001 and 11-001 enrolled pediatric patients with newly diagnosed B- or T-ALL from 2005 to 2011 and from 2012 to 2015, respectively. Protocol therapy was nearly identical for patients with T-ALL (N = 123), who were all initially assigned to the high-risk arm. End-induction minimal residual disease (MRD) was assessed by reverse transcription polymerase chain reaction (RT-PCR) or next-generation sequencing (NGS), but was not used to modify postinduction therapy. Early T-cell precursor (ETP) status was determined by flow cytometry. Cases with sufficient diagnostic DNA were retrospectively evaluated by targeted NGS of known genetic drivers of T-ALL, including Notch, PI3K, and Ras pathway genes. RESULTS The 5-year event-free survival (EFS) and overall survival (OS) for patients with T-ALL was 81% (95% CI, 73-87%) and 90% (95% CI, 83-94%), respectively. ETP phenotype was associated with failure to achieve complete remission, but not with inferior OS. Low end-induction MRD (

We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). We included 6028 patients (median age, 6 years; interquartile range, 1-11; range

Background Survival disparities by race/ethnicity and socioeconomic status (SES) are observed in a wide range of pediatric treatment settings including oncology and solid organ transplantation. To date, few studies have examined the effects of race and SES on outcomes in pediatric allogeneic hematopoietic cell transplantation (HCT). We explored whether survival differed by race/ethnicity or SES in children receiving HCT for nonmalignant conditions at a single institution serving a diverse patient population. Procedures The Kaplan-Meier method was used to estimate overall survival (OS) with the log-rank test for between-group comparisons. Cox proportional hazards models were used to identify risk factors for OS, adjusting for treatment- and disease-related factors. Results Of 133 subjects, 0 to 21 years, 19% were non-Hispanic (NH) white, 34% were NH black, 40% were Hispanic, and 7% were Asian. Sixty-seven percent of the subjects had public insurance; 49% lived in neighborhoods with poverty rate ≥20%. Primary diagnoses included hemoglobinopathies (56%), bone marrow failure (22%), and other conditions (22%). Median follow-up was 5.8 years (range 0.1-14.5). Analysis revealed no difference in OS by race, insurance type, or neighborhood SES. Conclusions Findings from this single-institution study suggest that in pediatric patients undergoing HCT for nonmalignant conditions, treatment at a tertiary care center with a multidisciplinary approach may mitigate drivers of disparities observed in other settings. Additional studies are now needed to further elucidate the complex interrelationships among race, SES, and clinical outcomes for children undergoing HCT.

To ensure optimal clinical outcomes for patients while retaining adequate protection for donors, the National Marrow Donor Program developed guidelines specifying that up to 20 mL/kg of bone marrow can be harvested from donors. These guidelines, originally developed for unrelated adult donors, are followed in children as well. We studied the impact of granulocyte colony-stimulating factor (G-CSF) priming on the cellular composition of harvested bone marrow, sought to develop an algorithm to optimize bone marrow harvest volume from pediatric matched sibling donors, and studied the impact of CD34+ cell dose on clinical outcomes. We analyzed data from 92 bone marrow harvests and clinical outcomes for 69 sibling recipient-donor duos, The mean age of recipients was 9.85 ± 5.90 years, and that of donors was 11.85 ± 6.36 years. G-CSF priming was not associated with higher yield of CD34+ cells/µL. The median CD34+ cell count obtained from donors was 700 cells/µL (range, 400-1700 cells/µL) in donors age 12 years (P

Introduction: Allogeneic hematopoietic cell transplantation (HSCT) is a curative treatment option for children and adolescents with non-malignant disorders. Continued advances in HSCT have led to a growing population of long-term survivors. For these survivors, late occurring chronic health conditions or so-called "late effects" remain a challenge. We examined the cumulative incidence of selected late effects at 5- and 10-years post-HSCT in pediatric and adolescent patients transplanted for non-malignant diseases. Methods: A retrospective analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database was performed. Eligible patients (1 - 20 years) underwent HSCT between 1995 and 2012 for treatment of non-malignant disorders including marrow failure, red cell disorders, and immunodeficiencies (Table). Late effects evaluated were: avascular necrosis (AVN), cataracts, diabetes, growth hormone deficiency, hypothyroidism, gonadal dysfunction, renal failure requiring dialysis, and neurologic events (stroke and seizure). The cumulative incidence of each late effect was calculated at 5-years and 10-years from date of first report post-HSCT. Results: Median follow up was 94.1 months. A total of 5,858 patients from 230 centers were included. Median age at HSCT was 5.5 years. The majority (65%) of the patients were White race/ethnicity and 9% were Black, 60% were male. Diagnoses included: Marrow failure disorders, hemoglobinopathies, immunodeficiencies and immune-dysregulation syndromes (Table). The majority (62%) of the cohort received myeloablative conditioning (MAC), and a minority (16%) received total body irradiation (TBI). Among all patients, 19% had chronic graft-versus-host-disease (GVHD). Cumulative incidence estimates at 5- and 10-years post-HSCT are presented in the Table. One-third (28%) of patients had at least one late effect. Cumulative incidence estimates at 10 years included stroke/seizures (11.2%), renal failure (7.7%), growth hormone deficiency/disturbance (7.6%), gonadal dysfunction (4.2%), hypothyroidism (4.1%), cataracts (2.9%), and AVN (1.4%). For AVN, renal failure, and stroke or seizures, incidence was stable between 5 and 10 years. For endocrine-associated late effects, incidence increased over time, nearly doubling from 5 to 10 years (Table). Across the cohort, the probability of growth hormone deficiency increased from 3.7% at 5-years, to 6.5% at 10-years. Similarly, hypothyroidism increased from 2.7% at 5-years, to 4.5% at 10 years. The cumulative incidence of treatment-associated diabetes was 3.1%, with most cases occurring in the first-year post-transplant. Finally, the probability of cataracts at 10 years was 2.9%, which was double the incidence at 5 years. Conclusions Among children and adolescents undergoing HSCT for non-malignant diseases, cumulative incidence of late effects was overall low, and did not exceed 12% at 10 years. The timing of late effect development differed, with the cumulative incidence of AVN, diabetes, renal failure, and seizure/stroke staying fairly stable after 5-years. Diabetes occurred most frequently in the first year, which may be a reflection of steroids or other medications to manage graft-versus-host-disease during the early-post transplant period. In contrast, the incidence of endocrine-associated late effects including growth disturbance, hypothyroidism, gonadal dysfunction and cataracts nearly doubled between 5 and 10-years post-transplant. Findings from this work further emphasize the need for long-term follow-up and screening for late effects, particularly diabetes, renal disease and neurologic symptoms early post-transplant, and cataracts and endocrinopathies over time. Figure 1 Figure 1. Disclosures Hamilton: Syndax: Membership on an entity's Board of Directors or advisory committees; Equilium: Membership on an entity's Board of Directors or advisory committees. Schoemans: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: personal fees , Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants and personal fees; Gilead: Other: travel grants; CIBMTR: Consultancy, Other: travel grants; Janssen: Membership on an entity's Board of Directors or advisory committees; BHS: Membership on an entity's Board of Directors or advisory committees, Other: travel grants and personal fees , Research Funding; Jazz Pharmaceuticals: Other: personal fees; Takeda: Other: personal fees. Phelan: Amgen Pharmaceuticals: Research Funding.

Introduction: Increased toxicity with pegaspargase (PEG) in older and higher body mass index (BMI) patients (pts) with acute lymphoblastic leukemia (ALL) has recently led to dose capping practices. We assessed the influence of age, body surface area (BSA), and BMI on PEG-related toxicity and pharmacokinetics from two consecutive DFCI ALL Consortium trials without dose capping. Methods: Patient (pts) aged 1 to 0.1 IU/mL, was assessed 4, 11, 18, and 25 days after the Induction dose and nadir SAA was assessed before each Post-Induction dose. Asparaginase-related toxicities were prospectively assessed and graded by CTCAE version 3.0 (DFCI 05-001) or 4.0 (DFCI 11-001). Asparaginase toxicity for this analysis was defined as ≥1 of the following: pancreatitis, thrombosis, ≥grade 4 hyperbilirubinemia, ≥grade 4 hypertriglyceridemia. Allergy was analyzed separately (due to presumed dose independence). Height and weight at diagnosis were used for analyses. BMI categories were assigned using standard percentile ranges based on gender specific 2000 CDC growth charts. BSA was calculated using the Mosteller formula. Univariate analyses evaluated the relationship of age, BMI, and BSA with asparaginase toxicity. Comparisons of toxicity across BMI and BSA categories were performed using a Jonckheere-Terpstra test. Categorical comparisons for dichotomized BMI and BSA utilized a Fisher's exact test or chi square test. The relationships between BMI and BSA with toxicity were explored using multivariable models. Results: Between 4/2005-12/2011 802 pts enrolled on DFCI 05-001 and between 6/2012-6/2015 240 pts enrolled on DFCI 11-001. Both trials included random assignment of asparaginase formulation. In total 911 patients received pegaspargase during Induction and 351 during Post-Induction. During Induction, pts ≥15 years of age had higher asparaginase toxicity rates (17.1% vs 6.2%, p=0.0003) (Figure 1a). Toxicity differed significantly across BSA categories ( Post-Induction, age ≥15 years was associated with increased asparaginase toxicity (57.1% vs 21%, p Post-Induction, median nadir SAA levels were ≥0.1IU/mL for all BSA and age categories. Median SAA was similar or lower at all time-points for those ≥15 years of age compared with younger children. Median SAA for pts with BSA ≥1.5m 2 were similar or lower compared to those with BSA Conclusion: Age ≥15 years and BSA ≥2m 2 were each associated with significantly increased asparaginase toxicity. Older patients and those with higher BSA had similar or lower median SAA levels at all time-points. These results suggest that the differential toxicity seen in older patients and those with higher BSA is not explained by these patients having higher SAA levels. Prospective exploration of interventions to decrease toxicity in older patients and those with high BSA are needed. Figure 1 Figure 1. Disclosures Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership; Pharmacyclics: Research Funding. Silverman: Takeda, Servier, Syndax, Jazz Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees.

Introduction: Assessment of minimal residual disease (MRD) in a sensitive and timely manner is an essential component of risk stratification in childhood acute lymphoblastic leukemia (ALL). Next generation sequencing (NGS) assays utilize unique genetic sequences created by VDJ rearrangements in leukemia cells to detect MRD at the level of 1 leukemic cell in 1 million cells (Wood et al., 2018). Here we report our experience using NGS MRD for risk group assignment of children and adolescents with newly diagnosed ALL enrolled on the Dana Farber Cancer Institute (DFCI) ALL Consortium Protocol 16-001. Methods: Patients (pts) ages 1-21 years with B- or T-ALL were eligible for enrollment from 8 centers across the US and Canada. Initial risk status was assigned based on age, presenting leukocyte count, central nervous system (CNS) leukemia status, immunophenotype, and disease biology (Table 1). All patients underwent bone marrow evaluation at diagnosis and again upon completion of remission induction approximately four weeks later (Induction 1a, timepoint 1 (TP1)), with samples evaluated by flow cytometry (FCM) and NGS. NGS was primarily used for MRD-based risk determination, with FCM as a back-up test. Patients with high TP1 MRD (≥10 -4) received intensified therapy and underwent additional MRD assessments at 10 and 20 weeks of therapy. Multiparametric FCM was conducted locally for 7 of 8 sites in accordance with local CLIA certified lab practices. One site used centralized FCM. NGS MRD was assessed at Adaptive Biotechnologies Corporation, Seattle, WA using the commercially available assay ClonoSEQ ®. Clonality was evaluated at the immunoglobulin (Ig) heavy and light chain (IgH and IgL) and T cell receptor beta and gamma (TCR-B and TCR-G) loci with the maximal sequence used for MRD determination. Results: NGS evaluation of MRD is feasible A total of 317 patients enrolled on 16-001 between 2017 and 2020 were included in this analysis. Among this cohort, NGS identified unique trackable sequences in 98% of pts (N=310). Of the 7 pts without trackable sequences, 57% were pts with early T precursor (ETP) T-ALL (36% of all ETP pts tested). NGS detected trackable sequences in all non-ETP T-ALL pts (N=40), and 99% of B-ALL pts (N=263). Locus used for MRD determination Patients with B-ALL had a median of 5 trackable sequences (range 0-14) with 92% having at least one IgH and 64% having at least one TCR-G. For B-ALL, the highest MRD value at TP1 was determined by IGH locus in 44% (N=115) of pts and by TCR-G in 41% (N=109). The IgL or TCR-B locus yielded the highest TP1 MRD value in 15% (N=39). In contrast, pts with T-ALL had fewer trackable sequences with a median of 3 (range 0-8). While 28% (N=13) had at least one Ig sequence, the TCR locus was used for MRD determination in nearly all (98%, N=46) with 94% using TCR-G. Comparison of NGS and FCM MRD results NGS and FCM MRD values for 309 pts with results from both assays at TP1 are displayed in Figures 1a-d. Correlation was high between the two modalities for patients with detectable disease by both NGS and FCM (Pearson r=0.87, p For B-ALL pts with high MRD (N=70), 43% (N=30) were high by NGS (≥10 -4) when FCM was low ( Eight pts, all with B-ALL, had low NGS MRD when FCM was above the threshold of 10 -4. One patient had undetectable NGS MRD and the remaining 7 had NGS MRD in the range of 10 -6 to Conclusions: Delivery of risk adapted therapy for newly diagnosed pediatric pts with ALL utilizing an NGS MRD assay is feasible with evaluable MRD for 98% of patients in our cohort. Importantly, NGS identified more cases as having high MRD than FCM, with the majority of discrepant cases just above the FCM limit of detection (10 -4). NGS provided improved resolution in the range of 10 -6 to Figure 1 Figure 1. Disclosures Kirsch: Adaptive Biotechnologies: Current Employment, Current holder of stock options in a privately-held company. Silverman: Takeda, Servier, Syndax, Jazz Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees.

184 Background: Routine screening for financial hardship may identify patients at risk of financial crisis (bankruptcy or inability to afford food or medication). Identifying financial hardship risk is a critical step toward mitigating financial toxicity, associated with earlier mortality and poorer quality of life. We are studying the implementation of systematic financial hardship screening using the electronic health record (EHR) in a large, urban, outpatient cancer center. Methods: Guided by the Consolidated Framework for Implementation Research, we met with key stakeholders, including providers, medical assistants (MA’s), administrative staff, and patient advocates to develop a process to systematically screen all cancer patients for financial hardship risk using 2 items (Q1 and Q3) from the Comprehensive Score for Financial Toxicity (COST). We initiated the process in the breast oncology clinic and partnered with EPIC to integrate the items in the EHR and patient portal. In March 2021, we implemented systematic screening, with automatic prompts to reassess monthly. Results: The workflow includes two mechanisms for patients to complete the 2 items: through the online patient portal during appointment check-in; or through a paper form in English or Spanish, distributed to patients during check-in. An EHR flag was created to notify staff if the patient is due to complete the questions during check-in. During vital signs assessment, the MA collects the form and enters the responses into the EHR. Two important factors were identified to improve the implementation: 1) Patient support to facilitate EHR portal use to reduce clinic workflow congestion; and 2) printed resources for patients who express financial concern. Ongoing discussions reveal that certain clinic days are busier, during which staff find it difficult to review EHR flag, provide and collect paper forms. To date, of 1,358 patients seen in the breast oncology clinic, 526 (39%) have responded to the question, “I know that I have enough money in savings, retirement, or assets to cover the costs of my treatment,” and of those, 278 (53%) responded “not at all” or “a little bit.” Of the 532 patients (39%) who responded to the question, “I worry about the financial problems I will have in the future as a result of my illness or treatment,” 215 (40%) responded “quite a bit” or “very much.” Conclusions: Preliminary analysis highlights the complexities of initiating systematic financial screening in oncology clinics. However, interim results suggest financial hardship is prevalent. Next steps include: expanding to pediatric and gynecologic oncology; building a dashboard to inform financial referrals; comparison of the 2-item screener to the COST survey in a subset of patients; qualitative interviews and focus groups with patients and staff to improve current procedures and optimize the use of dashboards and alerts to focus interventions and referrals on patients most in need.

Lymphomas are responsible for approximately 20% to 25% of annual cancer diagnoses in the adolescent and young adult (AYA) population. In 2006, the National Cancer Institute and the Lance Armstrong Foundation developed a joint Adolescent and Young Adult Oncology Progress Review Group (AYAO-PRG) to formally address the unique cancer burden of patients age 15 to 39 years. As part of their recommendations, the AYAO-PRG identified 5 imperatives for improving outcomes of AYAs with cancer. Broadly, the recommended areas of focus included research, awareness and education, investigational infrastructure, care delivery, and advocacy. In response to the challenges highlighted by the AYAO-PRG, the Lymphoma Research Foundation held the first AYA Lymphoma Research Foundation Symposium on 2 October 2015. At this symposium, clinicians and basic scientists from both pediatric and adult disciplines gave presentations describing the state of the science and proposed a collaborative research agenda built on the imperatives proposed by the AYAO-PRG. The following review presents an in-depth discussion of lymphoma management across pediatric and adult oncologic disciplines, focusing on Hodgkin lymphoma, mature B-cell lymphomas, and anaplastic large cell lymphoma.

Introduction: Hypersensitivity reactions with asparaginase occur frequently in pediatric patients (pts) with acute lymphoblastic leukemia (ALL). The standard approach for pts with reaction to E.coli-derived asparaginase is to switch to Erwinia asparaginase, given concern that clinical reactions reflect presence of neutralizing antibodies; however, Erwinia requires more frequent dosing and is often unavailable. Therapeutic drug monitoring allows for discrimination between pts with pegaspargase hypersensitivity who have sub-therapeutic asparaginase activity and those still able to derive therapeutic benefit from pegaspargase. We prospectively piloted re-challenging pts with pegaspargase after initial Grade 2 hypersensitivity to this agent, with premedication at re-challenge and assessment of serum asparaginase activity (SAA). Methods: Pts aged 1 to < 22 years with newly diagnosed ALL were eligible for DFCI 16-001. Pts received 1 dose of intravenous pegaspargase during Induction, and every 2 weeks for 15 total doses in Post-Induction phases, without routine premedication. Pts were monitored during/after pegaspargase for allergy, with CTCAE version 4.0 event grading. Those with ≥Grade 3 allergy discontinued pegaspargase and were switched to Erwinia. Those with Grade 2 allergic reaction were eligible for pegaspargase re-challenge with pre-medication (acetaminophen, diphenhydramine, and hydrocortisone, or per institutional standard) and slower infusion rate. If < 50% of the intended dose had been administered when reaction occurred, re-challenge was within 1-7 days of initial reaction. If ≥ 50% of the intended dose had been given, re-challenge was at next planned pegaspargase dose. SAA was measured 1-hour, 7-days, and 14-days after the re-challenge infusion (if dose completed). If 1-hour or 7-day level ≥ 0.1 IU/mL, and 14-day level ≥ 0.025 IU/mL, SAA was considered adequate, and the pt continued to receive pegaspargase with premedication. Pts with an inadequate SAA level, or with new ≥ Grade 2 allergic reaction with the re-challenge dose were considered to have failed re-challenge and were changed to Erwinia (or enrolled on a clinical trial of recombinant crisantaspase, an alternative Erwinia preparation). Results: Between 3/2017- 7/2020, 317 eligible pts enrolled. Overall, 81 of 299 (27%) total evaluable pts experienced a first allergic reaction to pegaspargase, 68 pts with Grade 2 reaction, 13 with Grade ≥3. During Induction, 17 of 299 (6%) evaluable pts had allergic reaction to pegaspargase; all Grade 2. Of the 17 Grade 2 reactions, 13 pts (76%) underwent re-challenge in Induction, 9 (69%) re-challenges successful and 4 failed. Post-Induction, 64 of 241 evaluable pts (27%) had a first allergic reaction; 51 Grade 2 and 13 Grade ≥3. Thirty-six of 51 (71%) pts with Grade 2 allergy during Post-Induction underwent re-challenge, as did 1 additional pt with allergy during Induction who was re-challenged with first Post-Induction pegaspargase dose (per protocol guideline, due to receiving ≥50% of Induction dose). Among these re-challenges, 16 were successful, 21 failed. Overall, 25 of 50 (50%) pts who were re-challenged after Grade 2 reaction had a successful challenge and were able to continue pegaspargase. Among the 25 pts with failed re-challenge, 6 pts (24%) had inadequate SAA alone as cause of failure, 17 pts (68%) had an allergic reaction with the re-challenge dose, and 2 (8%) additional patients had both allergic reaction and documented inadequate SAA. Three pts who were successfully re-challenged had a subsequent allergic reaction to pegaspargase. Among the 22 pts who experienced another allergic reaction with pegaspargase (at re-challenge or subsequent dose), 19 pts (86%) experienced Grade 2, and 3 pts experienced Grade 3 reaction. Conclusion: Fifty percent of pts with a Grade 2 reaction to pegaspargase were able to tolerate and achieve adequate SAA when re-challenged with premedication. For those who did react with or after re-challenge, reactions were not more severe. The re-challenge approach limits premedication exposure only to a minority of pts with a history of prior reaction and substantially decreases the number of pts needing to switch to Erwinia asparaginase, which can be challenging to deliver due to administration schedule and drug shortage. Disclosures Place: Novartis: Consultancy, Other: Institutional Research Funding; AbbVie: Consultancy. Silverman:Takeda: Other: advisory board; Servier: Other: advisory board; Syndax: Other: advisory board.

Introduction While 5-year event-free (EFS) and overall survival (OS) in Hodgkin lymphoma (HL) generally exceed 85% and 95%, respectively, outcomes may not be as favorable in adolescents and young adults (15 - 39 years [y]) compared to children. Small clinical trials have reported better outcomes for pediatric but not adult patients with mixed cellularity (MC) vs. nodular sclerosing (NS) histology, suggesting the possibility of biologic differences across the age-spectrum in HL. We examined survival by age and histology in patients receiving risk-based, response-adapted therapy for de novo HL on contemporary Children's Oncology Group (COG) trials. Methods This was a pooled analysis of individual-level data from 1,907 patients enrolled on three Phase 3 COG clinical trials for treatment of low-risk (AHOD0431), intermediate risk (AHOD0031) and high-risk (AHOD0831) HL between 2002 and 2012. Histologic subgroups included MC, NS and classical HL, not-otherwise-specified (cHL, NOS). Five-year cumulative incidence of relapse, EFS and OS were compared by age group ( Results Between 2002 and 2012, N= 2155 patients 1 - 21 y enrolled on three COG trials, 1,907 (88%) of whom were included in this analysis. Mean age of the cohort was 14.6 y (± 3.5) with N= 871 (46%) Survival: Median follow up was 6.9 years. In unadjusted analyses, 5-year EFS and OS were 83% and 97%, respectively. The 5-year EFS was lower for patients ≥15 y vs. The effect of age on EFS varied by histologic subgroup. Among those with non-MC histology, cumulative incidence of relapse did not significantly differ by age in unadjusted models (Figure A), however 5-year EFS was significantly worse in the older group (Figure B). In multivariable analyses, age ≥15 y (vs. younger) was associated with a 1.3-fold increased risk of EFS (HR: 1.3; 1.03 - 1.7, p= 0.03) (Table). Among patients with MC histology, age ≥15 y (vs. younger) was associated with significantly higher relapse rate (22% vs. 5%, p< 0.01) (Figure C) and significantly worse 5-year EFS (75% vs. 94%, p< 0.01) (Figure D). This remained significant in multivariable models: patients with MC histology who were ≥15 y (vs. younger) had a 3.7-fold increased risk of EFS (HR: 3.7, 95% CI: 1.6, 8.9, p< 0.01) (Table). Conclusion In patients receiving response-adapted therapy for de novo HL on contemporary COG trials, adolescents ≥15 y had worse EFS and OS compared to younger groups. The magnitude of the effect of age was higher in patients with MC disease. Although recent pediatric trials in HL have indicated better survival for some children with MC histology, alternative approaches or novel therapies should be considered for older adolescents with MC disease, whose outcomes appear more like adults. Disclosures No relevant conflicts of interest to declare.

Introduction Survival disparities by race/ethnicity and socioeconomic status (SES) have been observed in a wide range of pediatric treatment settings. Few studies have examined the effects of ethnicity and SES in pediatric allogeneic hematopoietic cell transplantation (alloHCT). Objectives We explored whether survival differed by ethnicity or SES in children receiving alloHCT for non-malignant conditions at a single institution serving a diverse patient population. Methods The Kaplan-Meier method was used to estimate overall survival (OS) with the logrank test for between-group comparisons. Cox proportional hazards models were used for adjusted analyses of OS. Results Of 133 subjects from Conclusion Our findings suggest that in patients undergoing alloHCT for non-malignant conditions, treatment at a tertiary care center with a multidisciplinary approach may mitigate the health disparities seen in other treatment settings. Future research should include larger multicenter studies investigating the complex interrelationships among race/ethnicity, SES, and clinical outcomes in this understudied patient population. Occurrence of aGVHD was the only factor associated with inferior OS, emphasizing a need for better prevention and treatment strategies in children with non-malignant diseases.

Introduction: Hodgkin lymphoma (HL) is one of the most treatable cancers affecting adolescent and young adult (AYA) patients (15 - 39 years), however optimal therapy for de novo disease in this population remains a subject of debate. Population-based studies in HL consistently report a survival disadvantage for AYAs when compared with younger patients. Though the etiology of these disparities is unclear, analyses of clinical trials data suggest that observed survival differences may relate to treatment, rather than to age. Because registry analyses are often limited by lack of information about clinical characteristics and therapeutic exposures, the independent effect of age on HL-outcome outside of the cooperative group setting is unknown. To address this gap in the literature, we: (1) examined initial treatment regimen and patterns of care in a population-based cohort of AYAs compared to children with de novo HL, and (2) examined the impact of sociodemographic and clinical variables on overall survival (OS) and disease-specific survival (DSS) by age, after adjusting for therapy. Methods: Data for 4,426 patients aged 0 - 39 years diagnosed with classical HL between 2007 and 2016 were obtained from the California Cancer Registry (CCR). Detailed treatment information for each patient was extracted from unstructured free-text fields in the CCR database. Chemotherapy regimens were classified based on standard treatment approaches for adult and pediatric HL (Table). Multivariable cox proportional hazards regression models were used to examine the influence of sociodemographic and clinical variables on OS and DSS, overall and by age group, and are presented as adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Models were adjusted for race/ethnicity, sex, insurance, neighborhood socioeconomic status, histology, stage, B symptoms, treatment location at a NCI (National Cancer Institute)-designated cancer center, and radiation therapy (RT). Results: Of the 4,426 patients in this cohort, 33% were Conclusion: In this large, population-based cohort of children and AYAs with HL, we observed that initial therapy varies, but that the majority of AYAs receive ABVD. Variation in therapy was largely insufficient to explain observed survival disparities, as older age, NHB and Hispanic race/ethnicity, and public or no insurance each conferred increased risk of death, even after adjustment for chemotherapy regimen. Further analyses examining comorbidities, treatment-related toxicities, and cause of death are ongoing. Disclosures No relevant conflicts of interest to declare.

PURPOSE Population-based studies of children and adolescents with Hodgkin lymphoma (HL) report a survival disadvantage in nonwhite—non-Hispanic black (NHB) and Hispanic—patients. Whether disparities persist after adjustment for clinical and treatment-related variables is unknown. We examined survival by race/ethnicity in children receiving risk-based, response-adapted, combined-modality therapy for HL in contemporary Children’s Oncology Group trials. PATIENTS AND METHODS This pooled analysis used individual-level data from 1,605 patients (younger than age 1 to 21 years) enrolled in phase III trials for low-risk (AHOD0431), intermediate-risk (AHOD0031), and high-risk (AHOD0831) HL from 2002 to 2012. Event-free survival (EFS) and overall survival (OS) were compared between non-Hispanic white (NHW) and nonwhite patients. Cox proportional hazards for survival were estimated for both de novo and relapsed HL, adjusting for demographics, disease characteristics, and therapy. RESULTS At median follow up of 6.9 years, cumulative incidence of relapse was 17%. Unadjusted 5-year EFS and OS were 83% (SE, 1.2%) and 97% (SE, < 1%), respectively. Neither differed by race/ethnicity. In multivariable analyses for OS, nonwhite patients had a 1.88× higher hazard of death (95% CI, 1.1 to 3.3). Five-year postrelapse survival probabilities by race were as follows: NHW, 90%; NHB, 66%; and Hispanic, 80% ( P < .01). Compared with NHW, Hispanic and NHB children had 2.7-fold (95% CI, 1.2 to 6.2) and 3.5-fold (95% CI, 1.5 to 8.2) higher hazard of postrelapse mortality, respectively. CONCLUSION In patients who were treated for de novo HL in contemporary Children’s Oncology Group trials, EFS did not differ by race/ethnicity; however, adjusted OS was significantly worse in nonwhite patients, a finding driven by increased postrelapse mortality in this population. Additional studies examining treatment and survival disparities after relapse are warranted.

In this population-based evaluation of adolescents and young adults (AYA) acute lymphoblastic leukemia (ALL), we describe patterns of care (POC) and outcomes regarding hematopoietic cell transplantation (HCT) in first complete remission (CR1). Data were abstracted from the 2013 United States Surveillance, Epidemiology, and End Results POC study; newly diagnosed AYA ALL were included. Multivariable logistic regression evaluated associations with HCT in CR1; Cox proportional hazards regression evaluated survival associations. Of 399 AYAs with ALL included, 102 (28.5%) underwent HCT in CR1. High-risk cytogenetics (odds ratio [OR] = 4.86, 95% confidence interval [CI] = 3.02-7.83) and hyper-cyclophosphamide, vincristine, adriamycin, and dexamethasone (CVAD) induction (OR = 1.84, 95% CI = 1.07-3.16) were associated with HCT in CR1. Two-year cumulative incidence of relapse, relapse-free survival (RFS), and overall survival (OS) of the entire cohort were 28.3% (95% CI = 23.4-33.4), 69.3% (95% CI = 63.6-74.3%), and 84.1% (95% CI = 79.7-87.5), respectively. Two-year RFS was significantly higher in patients receiving CR1 HCT relative to chemotherapy (83.6%, 95% CI = 72.6-90.5% vs. 64.3%, 95% CI = 57.5-70.3), but no difference was seen in 2-year OS (88.9%, 95% CI = 80.8-93.7 vs. 82.5%, 95% CI = 77.2-86.7). Treatment at a nonteaching hospital was independently associated with inferior OS (hazard ratio = 2.15, 95% CI = 1.23-3.76). Although the ALL landscape is changing, these data provide a snapshot of the use and outcomes of HCT for AYA ALL across the United States.

10025 Background: Poverty is associated with inferior psychosocial function among parents of children with cancer. Severe parental distress during treatment predicts future poor mental health for both parents and children. It is also associated with impaired parental cognitive bandwidth and executive function, which may have implications for treatment adherence. Efforts to identify poverty-exposures amenable to intervention are essential to improving survivorship quality of life for the > 90% of children with acute lymphoblastic leukemia (ALL) who will be long-term survivors. Household material hardship (HMH) is a targetable poverty exposure defined as at least 1 of 3 unmet basic needs including food, housing, or utilities. Dana-Farber Cancer Institute (DFCI) ALL Consortium trial 16-001 is the first pediatric oncology clinical trial to systematically evaluate HMH. We investigated the hypothesis that HMH exposure independently predicts severe parent psychological distress during ALL therapy. Methods: Patients with newly diagnosed ALL ages 1-17 years were enrolled on the DFCI 16-001 embedded HMH cohort study at 8 U.S. and Canadian centers. Secondary interim analyses used baseline (within 32-days of trial enrollment) and 6-mos parent-reported sociodemographic data, the Kessler-6 (K6) Psychological Distress scale, and trial-collected child and disease data. Severe psychological distress was defined as a K6 > = 13. Multivariable cox regression evaluated baseline HMH-exposure and parent distress at baseline and 6-mos adjusting for child’s initial ALL risk group (Very High Risk (VHR) vs other) and marital status (single vs dual parent). Results: Among 258 families with evaluable data, 34% reported baseline HMH. Families were predominantly English-speaking (54%) dual parent households (71%). Children were a median of 5.7 years (IQR 1.0-17.99) at diagnosis and predominantly non-Hispanic white (66%) with expected disease distribution by immunophenotype (84% B-cell). HMH (odds ratio (OR) 2.18, 95% confidence interval (CI) 1.0-4.31, p = 0.025) and VHR initial risk group (OR 2.32; 95% CI 1.06-5.06, p = 0.035) were independently associated with baseline severe psychological distress. Only HMH was independently associated with 6-mos severe psychological distress (OR 4.93, 95% CI 1.80-13.48, p = 0.002). Future analyses will investigate race and ethnicity associations with parental distress pending trial accrual for statistical power. Conclusions: HMH, a modifiable poverty exposure, is significantly associated with severe parent psychological distress at diagnosis that persists 6-months into pediatric ALL therapy. These findings identify a cohort at high risk of inferior mental health outcomes, and affirm the need for HMH-targeted interventions to support children and parents during cancer treatment to reduce poverty-associated outcome disparities in survivorship.

Medulloblastoma (MB) is the most common high-grade primary brain malignancy in children and accounts for 1% of adult brain tumors. Previous studies have compared survival in pediatric and adult MB from the National Cancer Institute Surveillance Epidemiology and End Results (SEER) database finding no difference. However, diagnostic subgroup analyses are limited. We examined survival in children (age 0–19) and adults (20–79) coded as MB in the 2018 SEER database (2000–2016), using Kaplan Meier analysis, log-rank test and Cox proportional hazard ratios (HR) with 95% confidence intervals (CI).). MB in SEER-18 is defined as ICD-O-3 histology codes 9470–9474 (n=1,728). ICD 9473, supratentorial PNET (sPNET, n=97) is biologically distinct so was analyzed separately. 5-year survival for MB, excluding sPNET, was similar in children (n = 1,091, 75.3%) and adults (n= 488, 79.1%) (HR=0.97, CI: 0.79 – 1.17, p=0.50). Subtype analyses showed no survival difference comparing adults and children with desmoplastic nodular MB (n=222, p=0.09), large cell MB (n=73, p=0.46), or MB NOS (n=1330, p=0.10). In contrast, children with sPNET had improved survival (n=65, 72.3%) compared to adults (n=29, 51.7%) (HR = 2.0, CI: 1.10 – 3.92; p=0.02,). In conclusion, 2018 SEER data for MB continue to show no survival difference between adults and children, suggesting adult patients could appropriately be entered on pediatric MB treatment protocols. Further analyses of the 2018 data are ongoing adjusting for sex, race, and treatment. Comparison of adults and children with MB and sPNET will be re-evaluated using the new 2016 World Health Organization classification.