Adolescents And Young Adults Population Research Articles

Analyzing the gut microbiome in adolescent and young adult patients with melanoma receiving immune checkpoint blockade.

9563 Background: Melanoma is the third most common cancer in adolescent and young adults (AYA), a unique cohort defined as patients between 15-39 years of age per the National Cancer Institute. Immune checkpoint inhibitors (ICI) have changed the landscape for advanced melanoma treatment, and the gut microbiota has been shown to remodel the tumor microenvironment to improve ICI efficacy. There is a paucity of research in this cohort, however studies show that AYA patients, in general, have historically not seen the same survival gains as other age groups. Furthermore, literature shows that survival was much worse for AYA's with stage IV melanoma than observed among older adults. Methods: The AYA cohort in this retrospective review is from the 2021 Science publication entitled "Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response". This cohort was matched on a 2:1 basis with older non-AYA patients 50-70 years of age. We controlled for sex, BMI, race, treatment naivety, stage of disease, as well as smoking, drug, and alcohol status. Results: Our AYA cohort of 23 patients is comprised of 15 females, 22 Caucasians, 20 with primary cutaneous melanoma, 12 with stage III at the start of treatment and 11 with stage IV, 17 were BRAF positive, 8 received combined immunotherapy, 20 were treatment naïve, and 11 were responders. We found no difference in alpha or beta diversity in AYA and older non-AYA patients, however alpha diversity increased with age. This is consistent with literature regarding aging gut microbiomes. Furthermore, we noted the most common microbes found between these groups varied considerably. Using differential analyses, we found, for example, a higher abundance of Ruminococcaceae, at the family level, in older non-AYA patients and a higher abundance of Bacteroides stercoris in AYA patients. Literature shows the relative abundance of Ruminococcaceae increased with age and was significantly higher in older patients. Furthermore, Bacteroides stercoris correlates positively with fiber, grain, and vegetable intake. Additionally, Blautia massiliensia, Blautia obeum, and Dorea longicatena were found to be significantly more prevalent (p=0.010, p=0.34, and p=0.035, respectively)) in older non-AYA patients. These species are all known to be obesity biomarkers. Conclusions: We found that the gut microbiota of AYA and older non-AYA melanoma patients differ. Older non-AYA patients have bacterial species associated with negative biomarkers which may be due to an aging gut microbiome. Establishing microbial features in the AYA population can help with microbiome modulation as a therapeutic strategy. Enriching modalities include fecal microbiota transplantation, probiotics, and improving diet as well as fiber intake. Further research should explore if the gut microbiome influences worse outcomes in AYA's with late stage melanoma.

"God is going to help me get through this": spirituality perspectives from Hispanic adolescent and young adult cancer survivors.

Describe spirituality's role in a sample of Hispanic adolescent and young adult (AYA) cancer survivors. This phenomenology-informed convergent parallel mixed-methods study aimed to explore participants' lived experiences with hope during cancer treatments and cancer survivorship. A purposive sample of Hispanic AYAs who completed cancer treatments 2-5years ago were virtually recruited for participation. Participants completed virtual semi-structured interviews about their experiences with hope during cancer treatments and cancer survivorship and prepared narratives about their experiences. Thematic analyses were iteratively performed across the data set to identify final themes. Ten Hispanic AYA cancer survivors (mean age 30.2, SD = 4.5) years participated in this pilot study. Seven participants (70%) were female, and three participants (30%) were male. Six participants (60%) experienced non-hematologic malignancies, and four participants (40%) experienced hematologic malignancies. Eight (80%) participants' language preference was Spanish, while two (20%) participants' language preference was English. The theme spirituality and subthemes living by faith, god as a resource, and spiritual gratitude were identified as concepts participants linked to their conceptualization of hope during cancer treatment and survivorship. Hope and spirituality may be conceptually linked to coping behaviors among Hispanic AYA cancer survivors. Hope through faith may be a learned spiritual value in Hispanic AYAs and might play a role in their spiritual and cognitive development. Further research is needed to explore the potentially protective value of hope and spirituality for the Hispanic AYA population.

Abstract SY15-02: Health insurance and outcome disparities in adolescents and young adults with cancer

Abstract SY15-02: Health insurance and outcome disparities in adolescents and young adults with cancer

A Scoping Review of Oncosexology Policy and Practice Tools Focused on Adolescents and Young Adults.

Background: Despite being considered a key component of quality-of-life, sexual health concerns in adolescents and young adults (AYA) patients with cancer (aged 15-39 years old) are often unmet due to barriers from both patients and health care professionals (HCPs). Investigation into policy and practice tools in this scope of practice is also limited. Aim: To review the literature on policy and practice tools in AYA oncosexology. Method: A scoping review was conducted using four databases: Medline, EMCARE, EMBASE, and PsycINFO, based on the Joanna Briggs Institute Scoping Review methodology. Retrieved articles were extracted into Covidence, followed by two screening rounds. Descriptive and basic content analyses were performed for evidence synthesis. Results: Seventy-four articles were included after screening rounds and citation searches. Overall, oncosexology policy and practice tools were categorized into screening tools (11 articles), guidelines (38 articles), training programs (15 articles), service delivery initiatives (5 articles), and the evaluation of their feasibility/challenges to implementation (5 articles). Among these, only ten articles were specifically about the AYA population. They helped identify and resolve sexual health concerns in AYA patients with cancer by providing strategies to overcome communication barriers, treatment options, and information resources for patients, and by advocating for more HCP education on this topic. Conclusion: The results warrant the need for more research, implementation and expansion of policy and practice tools for sexual health issues in AYA patients with cancer.

Venetoclax Combination Treatment of Acute Myeloid Leukemia in Adolescents and Young Adult Patients.

Over the past two decades, the prognosis in adolescents and young adults (AYAs) diagnosed with acute myeloid leukemia (AML) has significantly improved. The standard intensive cytotoxic treatment approach for AYAs with AML, consisting of induction chemotherapy with anthracycline/cytarabine combination followed by consolidation chemotherapy or stem cell transplantation, has lately been shifting toward novel targeted therapies, mostly in the fields of clinical trials. One of the most recent advances in treating AML is the combination of the B-cell lymphoma 2 (Bcl-2) inhibitor venetoclax with hypomethylating agents, which has been studied in elderly populations and was approved by the Food and Drug Administration (FDA) for patients over 75 years of age or patients excluded from intensive chemotherapy induction schemas due to comorbidities. Regarding the AYA population, venetoclax combination therapy could be a therapeutic option for patients with refractory/relapsed (R/R) AML, although data from real-world studies are currently limited. Venetoclax is frequently used by AYAs diagnosed with advanced hematologic malignancies, mainly acute lymphoblastic leukemia and myelodysplastic syndromes, as a salvage therapeutic option with considerable efficacy and safety. Herein, we aim to summarize the evidence obtained from clinical trials and observational studies on venetoclax use in AYAs with AML. Based on the available evidence, venetoclax is a safe and effective therapeutic option for R/R AML AYA patients. However, further research in larger cohorts is needed to confirm these data, establishing the benefits of a venetoclax-based regimen for this special population.

Abstract 3955: A proteogenomic study of high-grade glioma among adolescents and young adults

Abstract To unravel the molecular mechanisms underlying high-grade glioma (HGG) in adolescent and young adult (AYA) patients, we conducted a comprehensive proteogenomic analysis for 34 AYA (age 15-40) and 59 pediatric (age 0-15) HGG cases. Our approach involved whole genome sequencing, methylation profiling, RNA sequencing, and a suite of mass spectrometry-based proteomic experiments, including global proteomic, phosphoproteomic, and glycoproteomic profiling. The proteomics study successfully identified and quantified approximately 11,000 proteins, 33,000 phosphosites, and 3000 glycopeptides with a 50% missing filtering threshold. To identify the unique characteristics of AYA HGG in contrast to both pediatric and adult HGG, we further integrated a proteogenomic dataset of 99 adult GBM tumors previously published by CPTAC and collaborators (PMID: 33577785). Our study unveiled a collection of mutations, copy number variations, epigenetic modifications and gene fusions that exhibited different frequencies across tumors from pediatric, AYA, and adult patients. Moreover, the influence of these genetic variations on RNA/protein activities also varied across different age groups. Clustering analysis using age-dependent molecular profiles revealed striking differences in RNA/protein/phosphosite activities between patients aged 15-26 and 26-40. Additionally, significantly better overall survival (OS) was observed in the 26-40 age group compared to all other age groups, highlighting distinct biological characteristics within the AYA category that differentiate adolescents from young adults.By leveraging proteogenomic datasets from normal brain tissues (PMID: 30518843), we identified genes, proteins, and pathways with differential age-dependent molecular profiles between tumor and normal brain tissues. Notably, this analysis highlighted significant alterations in proteins from the oxidative phosphorylation, tricarboxylic acid (TCA) cycle, and myelin sheath pathways in tumors compared to normal tissues, some of which were found to be sex-specific.To search for prognostic markers, we introduced a novel approach called Trans-Population Survival Analysis through Interpolation of Age-Dependent Tumor Molecular Profiles. Applying this method on the kinase activity scores derived from the phosphoproteomic data, we identified 150 kinases whose activities were significantly associated with OS among AYA patients. Additionally, employing a causal network analysis tool, we pinpointed six kinases causally linked to OS, suggesting their potential as treatment targets. This study not only characterizes the molecular landscape of AYA HGG but also explores the disease trajectory across the lifespan. Our findings shed light on the intricate interplay of various factors influencing glioma etiology and patient outcomes, paving the way for a deeper understanding of HGG in the AYA population. Citation Format: Nicole Tignor, Mateusz P. Koptyra, Shrabanti Chowdhury, Weiping Ma, Jo Lynne Rokita, Marina Gritsenko, Xiaoyu Song, Giacomo B. Marino, Eden Z. Deng, Francesca Petralia, Azra Krek, Dmitry Rykunov, Felipe da Veiga Leprevost, Noshad Hosseini, Komal S. Rathi, Yingwei Hu, Simona Migliozzi, Tomer Yaron, Weijia Fu, Bo Zhang, Yuankun Zhu, Miguel A. Brown, Jeffrey R. Whiteaker, Clinical Proteomics Tumor Analysis Consortium (CPTAC), Children’s Brain Tumor Network (CBTN), Mehdi Mesri, Ana I. Robles, Karin Rodland, Lewis C. Cantley, Antonio Iavarone, Kenneth Aldape, Marcin Cieślik, Alexey I. Nesvizhskii, Joseph E. Ippolito, Joshua B. Rubin, Amanda G. Paulovich, Hui Zhang, Avi Ma'ayan, Tao Liu, Phillip B. Storm, Adam C. Resnick, Brian R. Rood, Pei Wang. A proteogenomic study of high-grade glioma among adolescents and young adults [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3955.

Co-delivery of HIV pre-exposure prophylaxis (PrEP) and HIV testing among publicly insured adolescents and young adults (AYA) receiving medication for opioid use disorder (MOUD)

BackgroundLow rates of HIV pre-exposure prophylaxis (PrEP) prescribing contribute to the disproportionate burden of HIV in the United States. Among adolescent and young adults (AYA) with opioid use disorder, HIV testing and PrEP co-prescription rates are poorly characterized. MethodsWe performed a retrospective analysis involving deidentified data from Philadelphia’s Medicaid beneficiaries ages 16–29 years who were prescribed medication for opioid use disorder (MOUD) from 2015 to 2020 and continuously Medicaid-enrolled for ≥6 months prior to that prescription. After identifying the presence of a qualifying diagnosis signifying a PrEP indication, we examined the outcome of appropriate PrEP co-prescriptions and HIV testing using generalized estimating equations (GEE) modeling. ResultsWe identified 795 AYA Medicaid beneficiaries with 1269 qualified treatment episodes. We calculated a PrEP prescribing rate of 29.47 per 1000 person-years among AYA receiving MOUD. The HIV testing rate was 63.47 per 1000 person-years among AYA receiving MOUD. GEE modeling revealed that individuals receiving methadone were more likely (aOR=2.62, 95% CI=1.06–6.49) to receive HIV testing within 6 months after a PrEP-qualifying diagnosis compared to those receiving other MOUD medications. Those who only saw outpatient behavioral health providers were less likely (aOR=0.48, 95% CI=0.24–0.99) to have received an HIV test within 6 months after the PrEP-qualifying diagnosis compared to those receiving inpatient behavioral health services. ConclusionsCo-prescription of PrEP and HIV testing among AYA receiving MOUD was rare in this large urban publicly insured population. Interventions are needed to increase HIV prevention services for this key population of AYA at risk for HIV infection.

Brain Tumor Imaging in Adolescents and Young Adults: 2021 WHO Updates for Molecular-based Tumor Types.

Published in 2021, the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) introduced new molecular criteria for tumor types that commonly occur in either pediatric or adult age groups. Adolescents and young adults (AYAs) are at the intersection of adult and pediatric care, and both pediatric-type and adult-type CNS tumors occur at that age. Mortality rates for AYAs with CNS tumors have increased by 0.6% per year for males and 1% per year for females from 2007 to 2016. To best serve patients, it is crucial that both pediatric and adult radiologists who interpret neuroimages are familiar with the various pediatric- and adult-type brain tumors and their typical imaging morphologic characteristics. Gliomas account for approximately 80% of all malignant CNS tumors in the AYA age group, with the most common types observed being diffuse astrocytic and glioneuronal tumors. Ependymomas and medulloblastomas also occur in the AYA population but are seen less frequently. Importantly, biologic behavior and progression of distinct molecular subgroups of brain tumors differ across ages. This review discusses newly added or revised gliomas in the fifth edition of the CNS WHO classification, as well as other CNS tumor types common in the AYA population.

Examining the prevalence of nicotine vaping and association of major depressive episodes among adolescents and young adults by disability type in 2021

BackgroundNicotine vaping is more prevalent among U.S. adults with disabilities compared to those without disabilities. However, less is known about nicotine vaping among adolescents (12–17 years) and young adults (18–25 years) by disability status. MethodsUsing data from a sample of 24,722 adolescents and young adults (AYAs) from the 2021 National Survey on Drug Use and Health, we conducted descriptive and multivariable analyses to estimate the national prevalence of nicotine vaping by disability type and examined major depressive episodes (MDEs) as a risk factor for nicotine vaping. ResultsA greater proportion of AYAs with disabilities engaged in past-month nicotine vaping compared to those without a disability (13.9 % vs 9.6 %, p = 0.0001). Also, when MDE was excluded from the model, AYAs with any disability had higher odds of nicotine vaping (AOR = 1.41; 95 % CI 1.15, 1.74) than those without a disability. However, disability status was no longer significant when MDE was included (AOR = 1.16; 95 % CI 0.91, 1.46) in the model. ConclusionsThe higher prevalence of nicotine vaping among AYAs with disabilities suggests that tailored messages may be needed to communicate health risks and adverse outcomes of e-cigarette use. Also, MDE is associated with nicotine vaping among AYA populations. This information can be helpful to school nurses, counselors, and mental health professionals in their screening of major depression as a risk factor for e-cigarette use.

BRCA Mutations and Fertility Preservation.

Hereditary cancers mostly affect the adolescent and young adult population (AYA) at reproductive age. Mutations in BReast CAncer (BRCA) genes are responsible for the majority of cases of hereditary breast and ovarian cancer. BRCA1 and BRCA2 act as tumor suppressor genes as they are key regulators of DNA repair through homologous recombination. Evidence of the accumulation of DNA double-strand break has been reported in aging oocytes, while BRCA expression decreases, leading to the hypothesis that BRCA mutation may impact fertility. Moreover, patients exposed to anticancer treatments are at higher risk of fertility-related issues, and BRCA mutations could exacerbate the treatment-induced depletion of the ovarian reserve. In this review, we summarized the functions of both genes and reported the current knowledge on the impact of BRCA mutations on ovarian ageing, premature ovarian insufficiency, female fertility preservation strategies and insights about male infertility. Altogether, this review provides relevant up-to-date information on the impact of BRCA1/2 mutations on fertility. Notably, BRCA-mutated patients should be adequately counselled for fertility preservation strategies, considering their higher sensitivity to chemotherapy gonadotoxic effects.

Challenges and limitations of clinical trials in the adolescent and young adult CNS cancer population: A systematic review.

The adolescent and young adult (AYA) cancer population, aged 15-39, carries significant morbidity and mortality. Despite growing recognition of unique challenges with this age group, there has been little documentation of unmet needs in their care, trial participation, and quality of life, particularly in those with primary brain tumors. A systematic literature review of 4 databases was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Studies included editorials, reviews, and practice guidelines on the challenges and limitations faced by the AYA population. Papers had to address CNS tumors. Sixty-eight studies met the inclusion criteria. The challenges and limitations in clinical trials in the AYA population were synthesized into 11 categories: molecular heterogeneity, tumor biology, diagnostic delay, access to care, physician factors, patient factors, primary brain tumor (PBT) factors, accrual, limited trials, long term follow up, and trial design. The published papers' recommendations were categorized based on the target of the recommendation: providers, coordination of care, organizations, accrual, and trial design. The AYA cancer population was found to suffer from unique challenges and barriers to care and the construction of trials. The AYA CNS cancer population suffers from unique challenges and barriers to care and construction of trials that make it critical to acknowledge AYAs as a distinct patient population. In addition, AYAs with primary brain tumors are underrecognized and underreported in current literature. More studies in the AYA primary brain tumor patient population are needed to improve their care and participation in trials.

Intrauterine Device Placement Success for Adolescents and Young Adults at Community-Based Reproductive Health Clinics

BackgroundDespite the endorsement of intrauterine device (IUD) use in adolescents and young adults (AYA) by leading professional organizations and demonstrated acceptance and desirability by AYA, clinicians may worry about procedural difficulty of IUD device placement in younger patients. ObjectiveThe aim of this study was to evaluate the clinical outcomes of first-attempt IUD placement in an AYA population by vaginal delivery (VD) history. Study DesignWe performed a retrospective cohort study of patients <25 years at reproductive health clinics with an IUD placement attempt between January 1-August 31, 2017. We abstracted sociodemographic characteristics, pregnancy history, and procedural characteristics including complications. Bivariate analyses compared successful first attempt IUD placement by VD history. We also assessed frequency of secondary clinical outcomes including ancillary measures used, provider type, symptoms reported during the procedure, and complications. ResultsWe included 1,325 participants (median age=21.3 years) including 42 (3.2%) with a prior VD. Nearly all IUD placements were successful at first attempt (n=1,301, 98.2%) and performed by advanced practice clinicians (n=1,314, 99.2%). First-attempt IUD placement success was similar in those participants with and without VD (p>0.999). Ancillary measures other than NSAIDS were used infrequently (n=16, 3.6%.) .(Among participants with an unsuccessful placement, 66.7% returned, and all had a successful IUD placement on the second attempt. Documented complications within six months of placement were rare (n=29) and mostly comprised of expulsions (n=27, 93.1%). ConclusionIUD placement success among AYA at community-based reproductive health clinics is very high and is not associated with a history of prior vaginal delivery.

Chronic Lymphocytic Leukemia (CLL) in Adolescents and Young Adults (AYA): Clinical Characteristics, Prognostic Factors and Survival for 498 Patients

Background Chronic lymphocytic leukemia (CLL) is primarily a disease of the elderly; however, it can also present in Adolescents and Young Adults (AYA) aged 15 to 39 years. Recent information of case series no larger than 227 patients each described clinical outcomes such as a 5-year Overall Survival (OS) of 90% and a 10-year OS of 78% for AYA 1-4. Data on the effect of age on OS in CLL is conflictive among studies 2,3. A higher proportion of males with CLL have been reported in the younger ages compared with olders in some series 2,4 but not in others 3. Sociodemographic characteristics and distribution between younger and older CLL patients have not been extensively reported 2-4. The objective of our study is to describe the clinical and sociodemographic characteristics, prognostic factors and survival in AYA diagnosed with CLL. Materials and Methods Cases of CLL were obtained from the Surveillance, Epidemiology, and End Results (SEER) Database from 2000 to 2020. Statistical analyses were conducted with SPSS® version 25. Patient characteristics were reported in frequencies and compared with the Chi-squared test. The Kaplan-Meier method was used to estimate the median Overall Survival (OS). Cox Regression was done to identify independent prognostic factors of survival. Results A total of 51,992 cases of CLL were identified. The median age of diagnosis was 69 years (interquartile range: 18 years). 498 AYA cases (1% of total population) were found (Table 1). For them, 66.1% were males, 70.3% were non-Hispanic whites and 90.2% lived in metropolitan areas. A median income of ≥$75,000 was noted in 45.6% of the patients. Chemotherapy was received by 32.7% and radiation therapy was given to 1.6%. The median OS for AYA population was not reached (Figure 1), with a 5-year and 10-year OS of 91% and 84%, respectively. OS was different between AYA vs older population, and age was found to be an independent prognostic factor for survival in the entire population of CLL (p&amp;lt;0.001, Figure 1). The age group comparison also found more proportion of males in AYA vs olders (66.1% vs 58.5%, p&amp;lt;0.001), more proportion of non-white patients in AYA group (29.6% vs 15.3%, p&amp;lt;0.001) and that AYA patients were more prone to receive chemotherapy (32.7% vs 14.8%, p&amp;lt;0.001). The multivariate analysis specific for AYA population found that American Indian/Alaska Native Non-Hispanic patients had poor prognosis compared with other races (HR=19.1, CI 95%: 2.2-166.5, p=0.008). Also, receiving radiotherapy (Beam radiation) was associated with poor prognosis (HR=5.5, CI 95%: 1.6-19.6, p=0.008). Compared to people with income &amp;lt;$35,000, all patients with higher income had better prognosis (for patients with ≥$75,000 median income the HR was 0.01, 95% IC: 0.001-0.11, p&amp;lt;0.001). Chemotherapy was not found to be an independent prognostic factor in this population (p=0.8). Conclusions To the best of our knowledge, this is the largest epidemiological study available for CLL in AYA to this date. Sociodemographic differences and epidemiologic prognostic factors described in this research contribute to understand this disease. Interventional studies are required to identify possible targeted therapies that could improve survival outcomes in this population. We believe that the differences in distribution and prognosis for the described variables in our study can contribute towards optimizing the randomization in interventional trials in the future.

Comparable Outcomes of Relapsed Acute Lymphoblastic Leukemia in Adolescents and Young Adults (AYA) Patients Treated with Pediatric-Inspired Chemotherapy (R3 protocol) Versus Adult-Based Salvage (FA) Protocol

Background Although the survival rate of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) has improved by using pediatric-based treatment protocols, those who experience a relapse still have poor outcomes when treated with adult chemotherapy salvage-regimens, which have traditionally included high doses of Ara-C. The long-term survival rate for patients treated with these salvage-regimens is less than 10%. Salvage treatment with blinatumomab for adults with relapsed B-cell ALL results in a complete remission (CR) rate of 34%, a median survival of 7.7 months, and an overall survival (OS) of less than 30% at 18 months. In contrast, the ALLR3 protocol for relapsed ALL in patients up to the age of 18 years achieved a CR rate of 97% and an overall survival rate of 72%. Therefore, this study aims to compare the outcomes of AYA patients treated with pediatric-inspired regimen (R3 regimen) to those treated with adult-based regimen (FA (Fludarabine/Cytarabine) protocol). Methods The R3 protocol treated 17 AYA patients with relapsed Philadelphia-negative ALL, aged between 14 to 40 years old, who had received first-line therapy. Patients who achieved CR underwent allogenic transplant. The protocol included vincristine, mitoxantrone, asparaginase, dexamethasone, and intrathecal methotrexate. In comparison, 60 patients were treated with FA protocol, with patients achieved CR proceeded to allogeneic stem cell transplantation. Relapses were classified as very early (&amp;lt; 18 months from diagnosis), early (&amp;gt;18 months from diagnosis and &amp;lt;6 months from the end of therapy), and late (&amp;gt;6 months from the end of therapy). Patients' characteristics, response rate (RR) and overall survival (OS) were analyzed. Results The two arms had comparable characteristics. The median age in the R3 arm was 16 years (range: 14-40 years) compared to 22 years (range: 18-32 years) in the FA protocol arm. In the R3 arm, 88.2% of patients had B-cell ALL, while in the FA protocol arm, 92.2% had B-cell ALL. CNS involvement was seen in 28.8% and 17.6% of cases in the R3 and FA protocol arms, respectively. Relapses were classified as very early, early, or late in 2 (12%), 5 (29%), and 7 (41%) of cases in the R3 arm and were mostly late (25.2%) in the FA protocol arm. Relapses in the R3 arm were isolated bone marrow (BM), isolated extramedullary (EMD), or combined BM and EMD in 14 (82%), 1 (6%), and 2 (12%) cases, respectively, while EMD was around three times higher (16.9%) in the FA arm. The overall CR rate was 60% at the end of R3 induction, with negative MRD (&amp;lt;10 −4 cells) in 47.1% of patients. The overall CR rate was higher in the FA arm (76.3%), but the difference with the R3 arm was not statistically significant (p-value 0.1). The disease was refractory to subsequent salvage therapy in 42% of cases in both arms. About half of the patients who responded to R3 proceeded to allogeneic stem cell transplant (52.3%), while 78% of the patients post-FA underwent transplantation. Eight patients died (47%) in R3 arm, but only one patient died due to treatment-related sepsis, while the other seven patients died due to disease-related causes. At a median follow-up of 4 years, OS was 53% in the R3 arm compared to 30.8% in the FA arm, but the difference was not significant (p-value=0.8). The post-FA mortality was mainly due to infections (15.3% in FA vs. 5.9% in R3). Conclusion Pediatric-inspired protocols that have shown significant benefits in the front-line setting for ALL in the AYA population did not demonstrate a significant difference when compared to traditional adult-based salvage chemotherapy regimens in relapsed disease.

Patterns of Care and Outcome in Adolescent and Young Adults (AYA) Lymphomas- a Multicenter HCC (Hematologic Cancer Consortium) Registry Study from India

Introduction There are no recommendations pertaining to lymphoma in AYA population. It represents a paramount opportunity for fostering collaborative research among pediatric and medical oncologists. Prior to embarking on any collaborative interventional research, comprehensive demographic data, patterns of care, and outcomes related to AYA lymphomas are imperative. Hence, the HCC registry database can be utilized to do this analysis of all AYA lymphoma in India which will set the benchmark for future research in this area. Methods This was a retrospective study including data from participating member centers of the HCC registry. Data was collected using an online data capture program, which is already in place as part of the HCC registry and has been in use for the past 5 years. Each center maintains its source documents and is responsible for data accuracy. All patients diagnosed with lymphoma between January 01, 2020, and June 31, 2022, were included in the study. The treatment patterns for AYA lymphomas vary from intensive protocols like in the pediatric age group to less intense protocols used in adults. This registry data captured this heterogeneity in treatment patterns and outcomes. The primary endpoint of the study was event-free survival (EFS) which was defined as the time from the first cycle of chemotherapy to progression, relapse, second malignancy, or death. The secondary outcomes were response rates and overall survival. Results The data was collected from eight participating centers of India out of which five are public sector hospitals and three are trust-based private hospitals. A total of 677 AYA lymphomas were registered between January 01, 2020, and June 31, 2022. Treatment was given to 582 patients and the follow-up data was available for 570 patients. The median age of the cohort was 23 years (IQR-19, 27) with 65% of them being males. Almost 50 % of patients had Hodgkin lymphoma and the rest were non-Hodgkin lymphoma (NHL) as depicted in Figure 1. Among NHLs; DLBCL, T-LBL, PMBCL, ALCL, and Burkitt lymphoma were seen in 113(17%), 39(6%), 36(5%),28(4%), and 19(3%) respectively. PETCT was done in 70% patients at baseline. Early-stage disease was seen in 233 patients (35%), advanced stage in 366 patients (56%), and 60 patients (9%) were not staged at baseline. Bulky mediastinum was seen in 1/4 th of the patients out of which the majority (85%) were Hodgkin lymphoma and PMBCL. Extra nodal site involvement was seen in 43% of patients out of which marrow involvement constituted almost half. Out of 677 patients, 582 patients (86%) received treatment at their respective centers and only 5 % of patients could not receive any treatment due to financial constraints. Among 298 treated cases of Hodgkin lymphoma, 245(82 %) patients received ABVD while escBEACOPP was given to 28(9%) patients. In DLBCL, out of 87 patients, 59(68%) received CHOP-R, 10(11%) received DA-REPOCH, 8(9%) received GMALL NHL protocol and the rest 10(11%) received other intensive regimens. Around one-third(36%) patients received radiation therapy out of which 90 patients (57%) received it as part of definitive treatment and 50 (31%) patients received it as consolidation to residual site. The median follow-up of the entire cohort was 13 months(IQR-8, 12). Out of 570 patients where follow-up was available, the overall EFS was 76. % ± 2.4%. The EFS outcome according to the histopathological subtype is depicted in Figure 2. Relapse or progression occurred in 72 patients (12.5%) out of which 50(72%) could receive any form of salvage therapy including transplant. The most common cause of death was progressive disease in 18 patients (50%) and death due to toxicity in 3(8%), and unknown causes in 16(40%) patients. The presence of bulky disease or bulky mediastinum did not have an impact on EFS outcome.There was no difference in EFS between DLBCL or High-grade B- NHL NOS. Conclusion This is the one of largest real-world data on AYA lymphoma. The majority were Hodgkin lymphoma followed by DLBCL. Most patients received adult-type regimens or Hodgkin as well as non-Hodgkin lymphoma. The use of radiation was high (1/3 rd) which could be due to a higher burden of bulky and mediastinal disease in our cohort. The EFS outcomes are comparable to the published literature. This data will set the benchmark for future collaborative studies in India and abroad for AYA lymphoma.

Patterns of Emergency Department Utilization of Adolescents and Young Adults Living with Sickle Cell in North Carolina

Introduction Despite improvements in survival and life expectancy in high-income countries, adolescent and young adults (AYAs) living with sickle cell disease (SCD) remain at significant risk for morbidity and mortality. Our previous work using group-based trajectory modeling (GTBM) has demonstrated that a subset of AYAs with SCD are at risk for significant morbidity with SCD with increased healthcare utilization, vasoocclusive pain episodes, and death, particularly after transition to adult care (Kayle et al., Pediatric Blood &amp; Cancer, 2018). Yet, there is limited insight into which AYAs with SCD are at high risk for poor outcomes. The objective of this study was to identify patterns of emergency department (ED) utilization of AYAs with SCD in NC as individuals age, with the overarching future goal of better predicting which individuals are at highest risk. Methods The NC Hospital Discharge Data (Inpatient, Ambulatory Surgery/Outpatient and ED Databases), 2013-2020 were used. A patient with SCD was defined as a patient who had three or more visits (inpatient, ambulatory surgery, or ED visit) with International Classification of Diseases 9 or 10 codes for SCD within a 5-year period. Date of birth, sex and zip code were used to link patients across the datasets. Demographic variables including age, sex, race and ethnicity were extracted from visit level data. ED visits were defined as all ambulatory ED visits and ED visits that resulted in inpatient admissions between 2013 and 2019. Descriptive statistics were calculated to describe the sample characteristics such as sex and race. The number of ED visits per year across age 14 to 30 years were used as longitudinal variables in GTBM to identify trajectories of latent classes of ED visits. The number of latent classes was determined by model-fit indices such as BIC and entropy. Results There were 3643 participants included in this study. Participants were 95% Black or African American, 53.8% female and 46.2% male, with age ranging from 14-30 years. Our GTBM models identified three latent classes of participants (Figure 1) with similar ED utilization at age 14 years, but divergent predicted annual ED trajectories beginning around 18 years of age. Class 1, comprising 95% of the participants (n=3463) and 54% female, had minimal ED utilization throughout all the years. Class 2, comprising 4% of the participants (n=150) and 51.3% female, had a steady increase in annual ED use, peaking at 20 visits per year by at age 24 years. Class 3, comprising 0.8% of the participants (n=30) and 47% female, had more extreme ED utilization, up to 80 visits per year at age 24 years. Conclusions Using a large longitudinal dataset, we demonstrate distinct patterns of ED utilization among AYAs with SCD by age. Although ED utilization was similar between the groups at age 14 years, a small proportion (~5%) of individuals accounted for the highest ED utilization at older ages. Additionally, amongst the patients with highest ED utilization, there was a marked increase in ED utilization from age 18-24 years, highlighting the highest risk ages within the AYA population, when there is often a transition from pediatric to adult care. There were slightly more males in the highest ED utilization class, highlighting potential gender differences in ED utilization. Our next steps will be to assess which clinical and social factors predict ED utilization trajectory. Limitations in this study include the use of hospital discharge datasets, which may have limited the capture of patients with infrequent acute care visits and limited our ability to examine the role of SCD genotypes and disease-modifying therapy use on ED utilization patterns. Despite these limitations, the study identifies distinct classes of ED use among AYAs with SCD. Understanding and predicting patterns of ED utilization are critical in targeting early interventions towards individuals with the highest risk of healthcare utilization and disproportionate risk for future morbidity.

Classic Hodgkin Lymphoma in Adolescents and Young Adults.

Hodgkin lymphoma (HL) represents one of the more common cancers occurring in adolescent and young adults (AYAs) age 15-39 years. Despite a generally high cure rate, age-related differences in HL biology and the optimal therapeutic approaches including supportive care and risks for long-term adverse effects in the AYA population remain understudied. After an overview of HL epidemiology and biology in the AYA population, this review will cover frontline pediatric and adult treatment approaches. Recently completed and ongoing studies will foster harmonization of risk group definition and trial eligibility criteria across the AYA spectrum, enabling more rapid progress. In addition to treatment approaches, an evolving holistic care approach to AYA HL will result in enhanced understanding of unique challenges, and continued improved short- and long-term outcome for these patients.

Fertility Preservation in Adolescents and Young Adults With Cancer: A Case-Based Review.

Adolescent and young adult (AYA) oncology patients are unique in many aspects of their care; fertility preservation (FP) is one of the most complex to address. In addition to the newly diagnosed AYA patient, there are growing numbers of AYA survivors of childhood cancer who present with concerns about their fertility. Emerging independence, emotional and intellectual growth, and development of an adult mindset are hallmarks of the AYA population; these transitions heighten the intrinsic medical, social, and financial challenges of a cancer diagnosis. FP is extraordinarily important in AYA oncology and can be addressed in many ways: experimental options as well as standard of care, with key differences on the basis of pubertal development, cancer diagnosis, and urgency of cancer-directed therapy. Options exist both at diagnosis and throughout the survivorship journey. It is imperative that oncologists recognize the challenges in this age group, as well as opportunities to pursue FP. The field has evolved significantly in the past 25 years and will continue to evolve as we incorporate more immune-based and targeted therapies into our treatment regimens. This case-based review will explore opportunities to preserve fertility in this unique patient population.

TMIC-59. IL-2 SECRETING ENGINEERED MYELOID CELLS POTENTIATE CYTOTOXIC EFFECTOR CELL ACTIVATION TO DELAY MALIGNANT PROGRESSION IN A PRECLINICAL MODEL OF GLIOMA

Abstract INTRODUCTION Gliomas are the most prevalent brain tumor in the adolescent and young adult population (AYA) and one of the leading causes of cancer-related death. In fact, two-thirds of glioma AYA patients are affected by low-grade gliomas (LGGs). Moreover, there are no therapies to prevent glioma LGG malignant progression. Malignant progression is associated with a significant reduction of tumor infiltrating cytotoxic effector immune cells, primarily due to the immunosuppressive tumor microenvironment (TME) mediated by regulatory T lymphocytes, tumor associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs). To that end, immunotherapies have had limited efficacy in improving outcomes for primary and secondary HGGs. HYPOTHESIS We hypothesize that engineered myeloid cells that release IL-2 will enhance the trafficking of activated effector T cells and potentiate a pro-inflammatory cascade in the low-grade glioma TME, delaying malignant progression. METHODS Immunocompetent RCAS n/tv-a LGG bearing animals were retro-orbitally treated at day 21 with a single dose of bone-marrow derived myeloid cells, engineered for the release of Interlekin-2 (GEMys-IL2). The inflammatory status of the TME along with the composition and functional status of tumor infiltrating immune cells were investigated in vivo by cytokine array, mass cytometry, and bulk RNA sequencing. RESULTS Our complementary dataset demonstrated that GEMys-IL2 infiltrated the glioma microenvironment and triggered a pro-inflammatory cascade involving the upregulation and release of IL2, IFNy, CXCL9, Tim1, CD26 and other pro-inflammatory cytokines associated with the activation and recruitment of innate and adaptive immune cells within the TME. In addition, we observed a downregulation of immunosuppressive signaling pathways such as IL10, PPAR, LXR/RXR, CTLA4 and PD-1. Also, a single dose of GEMys-IL2 systemically injected in RCAS/t-va immunocompetent LGG bearing mice potentiated pro-inflammatory remodeling of the TME and significantly improved overall survival. CONCLUSIONS These preclinical studies highlight a novel approach in developing next-generation innate immunotherapies.

Disparities Among Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia

Introduction: Acute lymphoblastic leukemia (ALL) in the pediatric population has a 5-year overall survival that exceeds 90%, however, the survival rate drops significantly in the adolescent and young adult (AYA) population. Notably, the AYA contribute to 80% of ALL mortality despite representing less than one-fourth of total ALL cases. The challenges related to caring for adolescents and young adults with malignancies have become increasingly well recognized and the impacts of racial, socioeconomic, and psychosocial disparities as potential contributors to AYA ALL survival rates are only recently being characterized. Methods: We conducted a retrospective cohort study using the Nationwide Inpatient Sample (NIS), the largest all-payer database of hospital admissions in the United States, from January 1, 2011 through December 31, 2020. The study sample consisted of AYA patients 15-39 years of age, as defined by the National Cancer Institute. ALL-related hospitalizations were captured using ICD-9 and 10 codes indicative of ALL. We performed temporal trends analysis to assess inpatient death among ALL hospitalizations by race/ethnicity using joinpoint regression. We used adjusted survey logistic regression analyses to assess associations between race/ethnicity and in-hospital mortality among ALL hospitalizations. Results: Our data captured 138,923 ALL-related hospital encounters of AYA patients from 2011 to 2020. In our cohort, 73.1% of ALL hospitalizations were in patients younger than 30, and 26.9% were in patients between the ages of 30 and 39. AYA NH-Black patients with ALL had twice the odds of inpatient mortality as compared to NH-White patients [odds ratio (OR), 95% confidence interval: 1.75 (1.34-2.29)] (Table 1). While the rate of inpatient mortality improved in the overall AYA population over our 10-year study period, strikingly, the rate of inpatient mortality instead increased in NH-Black patients (Figure 1). In contrast, NH-White patients saw the lowest rate of inpatient mortality, both at the start and at the end of our study period (Figure 1). Although the inpatient mortality rate in Hispanic patients improved over time, these patients remained at an increased likelihood of inpatient mortality compared to their NH-White counterparts [OR 1.32 (1.08-1.61)] (Table 1). Conclusion: Survival gains in the AYA population have improved only modestly compared to that of their pediatric and adult counterparts, and here we report that these survival gains are even further stratified and disparate depending on patient race/ethnicity with worse outcomes in NH-Black patients. It is important to better understand the disparities that impact the AYA population, which is particularly vulnerable to social factors impacting their care. Study limitations include lack of data pertaining to treatment received, including pediatric versus adult treatment protocol or bone marrow transplant status. Disparate access to centers of excellence, stem cell transplant and blinatumomab may certainly be contributors to the disparate outcomes described herein.