Adolescent And Young Adult Patients Research Articles

High Efficacy and Feasibility of a Full Pediatric Induction in Adults Aged up to 55 Years with Philadelphia-Negative Acute Lymphoblastic Leukemia

Background: Treatment of acute lymphoblastic leukemia (ALL) in adults has historically shown unsatisfactory outcomes when compared to the outstanding results obtained in pediatric patients. Pediatric protocols rely on increased drug intensity and on a tighter evaluation of minimal residual disease (MRD) for early intensification. Nowadays, pediatric-inspired protocols have been established as the standard of care for adolescents and young adult patients (AYA) leading to improved results. In the setting of older patients, probably due to the limited data available, the feasibility of such intensive therapies, and in particular the administration of high doses PEG-asparaginase (PEGASP), is still a matter of debate. In this context, the NOPHO group reported that a full-pediatric protocol was feasible and highly effective in adult patients, up to 45 years of age. Aim: The aim of our study was to evaluate the feasibility and efficacy of the entire full pediatric AIEOP-BFM LAL 2009 protocol in an older cohort of adult patients up to 55 years. Methods: Since May 2013, 28 consecutive adults diagnosed with Ph-neg ALL received first line therapy according to AIEOP- BFM-ALL 2009 protocol, which includes high PEG-asparaginase (PEGASP) doses, with an accurate MRD-driven therapeutic strategy. The protocol consists of 2 induction blocks: IA (Vincristine, Daunorubicin, PEGASP, IT methotrexate) and IB (Cytarabine, 6-mercaptopurine, cyclophosphamide, IT methotrexate), I consolidation block (high-dose methotrexate, 6-mercaptopurine, IT methotrexate), maintenance therapy (6-mercaptopurine, weekly MTX, IT Methotrexate). Median age in our study was 45 years (range 17-55), equal to the maximum age allowed in the NOPHO study. Fifteen patients had B-ALL, 13 T-ALL/T including 5 Early-T phenotype. Dose intensification and stem cell transplantation (SCT) were scheduled according to baseline and MRD-driven risk assessment. MRD was evaluated by multicolor-flow cytometry (MFC), with a threshold for positivity of 0.025%, and molecular PCR for JH rearrangement (MOL), with a sensitivity greater or equal to 10-4 in all patients. Patients with MOL MRD >10-4 but <10-3 were defined as low-level positive. MRD time points were day 33 and day 78 (MFC and MOL). Results: All patients achieved complete hematological remission following the first Induction course (100%). One patient died during induction due to infection by multidrug resistant P. aeruginosa. In general, therapy was well tolerated. Remarkably, patients in this study received high dose of PEGASP (median 10000 UI/sqm, equal to 4 administrations at 2500 UI/sqm each) without experimenting life threatening toxicities, which mostly consisted in asymptomatic elevation of transaminase (7 patients G3, 1 G4) and/or bilirubin (9 patients G3, 1 G4) only requiring supportive therapy. No major bleeding or thrombotic events o other >G2 toxicities were observed. All except one patient achieved CR at day 33 and all patients achieved CR at day 78. MFC MRD evaluation at day 33 resulted negative in 24/25 evaluable patients (95%). Day 33 MOL-MRD was evaluated in 22 patients, and resulted negative, low level positive or positive in 14, 5 and 3 patients, respectively. MRD assessment at day 78 showed both MFC and MOL negativity achieved in all 25 and 22 evaluated patients, respectively (Fig. 1). Four very high-risk patients underwent SCT in negative MRD status. After a median follow-up of 59 months (CI 95% 38.45-78.63), median survival was not reached, 5-years OS was 88.7% (Fig. 2). One patient died due to progressive transverse myelitis after isolated CNS relapse and one patient died due to sudden cardiac arrest while in complete MRD negative remission, 6 months after completion of therapy. All other 25 patients are alive and in complete MRD negative remission. Conclusion: The application of a full pediatric induction regimen in a cohort of adult ALL patients with a median age of 45 years proved to be feasible, with tolerable toxicities. In particular, we didn't observe major toxicities during the intensified PEGASP administration and all patients were able to receive the planned PEGASP doses. The possibility to maintain the correct timing translated in a very high MRD negativity rate and promising OS survival.

Benefit of Inpatient Pain Plan Utilization on Hospital Length of Stay in Adolescents and Young Adults with Sickle Cell Disease

Introduction Vaso-occlusive crisis (VOC) is the most common manifestation of sickle cell disease (SCD) and the most common cause for emergency department (ED) visits and hospital admissions. VOC accounts for approximately 230,000 annual admissions in children with SCD. Patients with SCD face inconsistent analgesic management, leading to high inpatient healthcare utilization and financial burden for healthcare institutions. Furthermore, patients describe their pain management as the area of their care in most need of improvement. A prospective longitudinal cohort study showed that implementation of individualized pain plans in adult patients with SCD significantly decreased the duration of VOC hospital stays by 1.2 days. A similar study in children showed no change in duration of hospital stay, however the study was limited by a small sample size. We hypothesized parallel results to the prior adult study in adolescent and young adult (AYA) SCD patients. Methods At UCSF Benioff Children's Hospital Oakland, we implemented inpatient pain plans for SCD patients with frequent VOC admissions (i.e., >1 VOC admission in the prior year or complicated VOC admission history). Pain plans are individualized and embedded into the patient's electronic health record. These plans include detailed daily analgesic recommendations with the general recommendation for discharge on day 5 of the pain plan. After IRB approval, we performed a retrospective chart review of SCD patients with individualized inpatient pain plans initiated between November 2017 and April 2022. We recorded baseline demographic information including age at pain plan initiation, SCD genotype and sex. We assessed length of inpatient hospitalization for VOC admissions in the year prior and the year after pain plan initiation for each individual patient. We also noted number of admissions secondary to VOC during this two year time period. Results Twenty-six patients with SCD and individualized pain plans were identified (Table 1). Average length of hospital stay for VOC was significantly decreased in the year after inpatient pain plan initiation (Table 2). There was a trend towards increased admissions due to VOC in the year after inpatient pain plan initiation (Table 2). Conclusions Similar to the prior adult study in SCD patients, we found significantly reduced inpatient length of hospitalization after initiation of an inpatient pain plan for AYA patients with SCD and VOC. Although there was a trend towards increased hospitalizations in the year after inpatient pain plan initiation, this was likely secondary to the average patient age with an expected increased in VOC year over year. The National Heart, Lung, and Blood Institute (NHLBI) SCD guidelines recommend an individualized prescribing and monitoring protocol be written by a SCD provider and used in patients withVOC to promote effective, timely, and safe analgesic management. We further demonstrate that individualized pain plans for AYA patients with SCD can decrease length of hospital stay due to VOC, likely secondary to more effective pain management recommendations that have been prior agreed upon by the patient/family and SCD provider. We currently are calculating morphine equivalents and hypothesize total opioid utilization will be concomitantly decreased due to this significantly decreased length of hospitalization.

Associations between the Use of Pain Management Strategies and Self-Reported Emotional and Behavioral Functioning of Adolescent and Young Adults with Sickle Cell Disease

Background: Sickle Cell Disease (SCD) often causes significant pain that may require the use of various pain management strategies. These strategies are typically categorized into two broad groups, pharmacological and nonpharmacological, but a need exists to understand how specific strategies may impact an individual's functioning. This understanding is especially critical when considering adolescents and young adults (AYA) with SCD, as this age range may experience increased pain and other SCD complications that coincide with the transition from pediatric to adult care. Methods: Adolescent and young adult patients with SCD completed the Behavioral Assessment System for Children, Third Edition (BASC-3), a measure of emotional and behavioral functioning, and a questionnaire about their pain management strategy use. These strategies were categorized as: Over the Counter Medication (acetaminophen, ibuprofen, naproxen), Prescription Medication (codeine, short-acting morphine, long-acting morphine, oxycodone, hydrocodone, hydromorphone, gabapentin, amitriptyline), Psychological Strategies (deep breathing, imagery, distraction, talking with friends/family, prayer/meditation), and Behavioral Strategies (hydrate, apply heat, apply cold, massage, smoking, rest/sleep). Analyses included Spearman rank correlations to determine the relationship between categories of pain management strategies and self-reported BASC scores. Based on correlation results, independent sample t-tests were conducted to further examine the relationship between the use of specific pain management strategies and self-reported BASC scores. Results: Participants included 94 AYA patients with SCD (Mean age = 18.1 ± 1.5 years; 51.1% female; 52.1% HbSS). Of the pain management categories, Prescription Medication and Behavioral Strategies had significant correlations with self-reported BASC scores. Within the Prescription Medication category, participants that reported use of hydrocodone (40.9%) self-reported higher scores on the Social Stress (p = 0.01) and Somatization (p = 0.001) scales of the BASC-3 as well as lower scores on the Interpersonal Relations (p = 0.048) scale compared to participants that did not use hydrocodone. Those using oxycodone (25%) self-reported higher scores on the Somatization (p = 0.002) scale and lower scores on the Interpersonal Relations (p = 0.036) scale compared to those that did not use oxycodone. Participants that reported use of gabapentin (6.8%) self-reported higher scores on the Social Stress (p = 0.006) and Somatization (p = 0.009) scales compared to those that did not use of gabapentin. Compared to participants that did not use amitriptyline, those that reported use (3.4%) self-reported higher scores on the Somatization (p = 0.017) scale. Within the Behavioral Strategies category, adolescents and young adults that reported the use of smoking to manage pain (7.3%) self-reported higher scores on the Somatization (p < 0.001) and Attention Problems (p < 0.001) scales than those that did not smoke. Additionally, participants that reported the application of cold temperature to manage pain (15.9%) self-reported higher scores on the Attitude to School (p = 0.03) and Attention Problems (p = 0.006) scales compared to those that did not use this strategy. Conclusions: Results indicate that specific pain management strategies may be associated with different social, emotional, and behavioral functioning. Further exploration to understand the mechanisms between specific pain management strategies and patient functioning during the AYA period is warranted. Given the unique challenges of adolescents and young adults with SCD, future work should also investigate how specific pain management strategies may improve the experience of those transitioning from pediatric to adult care.

Characteristics and Outcomes of Adolescent, Young Adults, and Adults 40-50 Years Old with Multiple Myeloma: A Single Center Experience

Background Multiple myeloma (MM) is a malignant tumor with abnormal proliferation of plasma cells. Adolescent and Young Adult (AYA) patients are defined as patients between 15-39 years of age. Multiple myeloma is uncommon in non-elderly populations. Its prevalence is only 2% in AYA age group and only 10% in patients 40-50 years old. The feature of MM is not well known or understood in those two age groups. In this retrospective study we describe the clinical characteristics, cytogenetics, prognostic markers, treatments given and outcomes of MM in AYA and 40-50 years old patients. Methods We retrospectively analyzed data from the clinical database of our single tertiary hematology center, The National Center for Cancer Care and Research, Doha, Qatar. This center serves a country's population of about 2,8 million people. All patients diagnosed with MM between the age 50 or less during the period of January 2007 to December 2022 were included. Results Seventy-four patients were diagnosed at our centre with MM before the age of 50 years, total of all MM cases 222 (33%) Males was predominant 55/74 (74.3 %) with a median age of 41 years (range, 15-49). Most of the patients were from Asian 55%. At diagnosis patients had a median hemoglobin of 10.2 g/dl, creatinine 294 umol/L, total protein 90 gm/L, albumin 34.75 gm/L, calcium 2.7 mmol/L, LDH 255 U/L, IgG 2289.75 mg/dl, IgA 424.15 mg/dl, IgM 34.2 mg/dl, FLC-Kappa 1993 mg/L and FLC-Lambda 1177 mg/L. Median of bone marrow filtration by plasma cell was 51 %. Most of the patients presented at advance stages with 44 patient (59%) presented as IIIA Durie Salmon or stage III and IV by ISS 70 %. IgG Kappa most frequent type of MM 18 patients (24%), followed by Free light chain kappa (23%), IgG Lambda (18%) and others including two cases of plasmacytoma (Most recurrent cytogenetics were diploid cytogenetics in 42 patients (57%), while 7 patients (9%) had complex cytogenetics. Twenty-eight patients had spinal cord compression at single or multiple levels ( thoracic were most common site 20%) while 3 patients had pathological fractures. Bortezomib based regimen is most one used to treat our patients. Daratumumab- Velcade, Revlimid, and dexamethasone (D-VRD) was used for 35 patients (74%) and Velcade,Cyclophosphamide and Dexamethasone VCD in 20 patients (27%). The first response to treatment showed completed remission (CR) in 35 patients, very good partial remission in 10 patients, partial response in 9 patients, four patients either refractory or primary refractory disease and one patient with stable disease. Thirty -five patients (48%) underwent their first autologous bone marrow transplant ASCT. A total of 8 patients underwent second ASCT and one patient underwent third ASCT. After a median duration of follow up of 6.25 years and 72 % of the patients were still alive. We compared the characteristics and outcome for the AYA group (18-39) with patient age group 40 to 49 years. Although there was no statistical significance difference between the two groups regarding overall survival (p=0.21) , the older group had more cases of spinal cord compressions and more cases of refractory disease. Patient characteristics are described in Table 1. Conclusion One third of MM patients in our center are younger than 50 years. These patients tend to present with advanced stage and serious manifestation such as spinal cord compression. IgG kappa and free light chain are the most common myeloma type in this cohort. D-VRD is the most used protocol with a good response rate. Patient characteristics and treatment outcomes are the same for AYA patients compared with patients 40-49 years old (p=0.21). Patients who received first transplant had better OS compare the those who didn't (p0.01)

Development of the Together - Teens&20s microsite, an online resource for adolescent and young adult cancer patients

ObjectivesThe purpose of this study was to explore the information needs and preferences of adolescent and young adult (AYA) cancer patients to guide next steps for development of a new online resource for this audience. The goals were to understand information needs, prioritize topic areas, and inform website design and functionality. MethodsParticipants were AYA cancer patients ages 13–25 years. We used multiple methods in two phases to gather audience feedback. The first phase collected quantitative data in an electronic survey (n = 45) about AYA patients' internet use and content preferences. The second phase collected qualitative data through focus groups (n = 13) about user preferences for content design and website function. ResultsSurvey results showed AYA patients were more interested in content about how treatments would impact their lives rather than the treatments themselves. They preferred content on school, careers, relationships, independence, side effects, and fertility. The focus groups indicated AYA patients prefer a clean, stylish design; infographics and visual aids; and the ability to find information quickly and control the amount they read. ConclusionsOnline resources represent an important opportunity to advance cancer education for AYA patients. However, it is important to consider the information needs and preferences of this audience in content design and delivery. InnovationPractitioners should use stakeholder input to guide the creation of patient education resources that are age- and audience-appropriate. This study provides insights into AYA information needs and preferences in pediatric oncology.

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.

Socioeconomic Disadvantage Is Associated with Decreased Long-Term Survival in Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia

Background: The treatment of acute lymphoblastic leukemia (ALL) in the adolescent and young adult (AYA) population has dramatically improved over the past decade with the use of pediatric-inspired regimens increasing long-term survival rates to over 60%. Despite these advances, AYA patients with ALL have seen persistent disparities in survival by race and ethnic background. The primary objective of this study is to examine socioeconomic disadvantage as a driver of the racial and ethnic disparities that exist among AYAs with ALL using a nationally representative cancer registry. Methods: The cohort was identified using the SEER*Stat software, which utilizes Surveillance, Epidemiology, and End Results (SEER) data from the National Cancer Institute (NCI). All SEER patients diagnosed at age 15 to 39 years with ALL from January 1, 2005 to December 31, 2019 were included in the analysis. Patients were excluded from analysis if they had an unknown cause of death, were diagnosed with ALL only postmortem, had no survival time listed, or did not have a recorded age. We utilized the area deprivation index (ADI) as a measure of socioeconomic disadvantage, and patients were excluded if they were in a county that did not have a corresponding ADI score (0.3%). ADI scores were calculated by county using the ‘Sociome’ package in R software. Both the 2009 and 2019 county ADI scores were used based on patient diagnosis year. ADI quartiles were then assigned by decade (2000-2009 and 2010-2019). The quartiles were calculated by first identifying the median ADI score for each decade, and then assessing the median of the lower and upper half to determine the lower and upper quartile value. Analyses were also completed by state Medicaid expansion status. Both cause-specific and observed survival (OS) were calculated by five-year periods from 2005 to 2019. The net survival time was assessed at 12 to 60 months in 12-month increments for 2005-2014 with only an upper limit of 48 months survival able to be calculated for patients diagnosed between 2015-2019. The Kaplan-Meier Method was used for all survival calculations. Results: A total of 4,382 patients were found to meet criteria for inclusion. Specific characteristics of the analyzed population are listed in Table 1. OS for the entire group was 60.6% at 60 months (95% CI 58.9%-62.3%), with a cause-specific survival at 60 months of 64.3% (95% CI 62.7%-65.9%). For AYA ALL patients diagnosed from 2005 to 2009, cause-specific survival for the ADI quartiles diverged over time and at 48 months was significantly higher in patients residing in a county with an ADI value of 1 (least disadvantaged) than in those residing in a county with an ADI value of 4 (most disadvantaged) [66.6%, 95% CI 62.5-70.4% versus 51.2%, 95% CI 40.2-61.2% p<0.05], although this difference was not significant at 60 months. This difference was also seen in OS at 48 months and persisted at 60 months [62.0%, 95% CI 57.9-65.8% versus 45.7%, 95% CI 35.3-55.5% (48 mo.) and 59.7%, 95% CI 55.6-63.5% versus 45.7%, 95% CI 35.3-55.5% (60 mo.) p<0.05]. There was no significant difference in cause-specific or OS by ADI quartile for patients diagnosed from 2010-2014. However, this difference in survival reoccurred in the most recent data available (Figure 1). For AYA ALL patients diagnosed from 2015 to 2019, cause-specific survival at 36 and 48 months was significantly higher in patients residing in a county with an ADI value of 1 than in those residing in a county with an ADI value of 4 [79.7%, 95% CI 75.6-83.2% versus 65.8%, 95% CI 55.8-74.0% (36 mo.) and 78.6%, 95% CI 74.2-82.3% versus 62.4%, 95% CI 51.8-71.3% (48 mo.) all p<0.05]. This difference was also seen in OS for all survival intervals from 12 to 48 months [90.2%, 95% CI 87.6-92.3% versus 81.3%, 95% CI 74.4-86.5% (12 mo.); 82.9%, 95% CI 79.4-85.8% versus 72.9%, 95% CI 64.9-79.3% (24 mo.); 77.1%, 95% CI 72.9-80.7% versus 62.1%, 95% CI 52.4-70.3% (36 mo.); and 76.0%, 95% CI 71.6-79.8% versus 58.8%, 95% CI 48.6-67.7% (48 mo.) all p<0.05]. There were no statistically significant differences noted in cause-specific and observed survival between states that expanded Medicaid versus those that did not. Conclusions: Socioeconomic disadvantage was associated with significantly worse long-term survival in AYA patients with ALL. This gap reappears over time despite both treatment innovations and public policy changes. Urgent interventional approaches are needed to target this highly vulnerable population.

Allogeneic Hematopoietic Stem Cell Transplantation in Adolescents and Young Adults with Acute Lymphoblastic Leukemia - Retrospective Dual-Center Study

Background: Adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) are treated with various chemotherapy regimens. Some patients undergo allogeneic hematopoietic stem cell transplantation (HCT) due to high-risk genetic characteristics, chemo-resistant disease (failure to achieve timely measurable residual disease (MRD) negative remissions, or relapse or refractory disease. There is paucity of data on outcomes of AYA ALL patients receiving HCT. Methods: We performed a dual-center analysis of data from MD Anderson Cancer Center (MDACC) and Dana-Farber Cancer Institute (DFCI) to evaluate outcomes of AYA patients who received HCT for Philadelphia-negative (Ph neg) ALL and examined variables that might have an impact on these outcomes. We included all patients who received their first HCT between the ages of 15-40 years between the years 2010-2022. MRD status was evaluated using flow cytometry with a sensitivity of 0.01%. Acute and chronic graft versus host disease (GvHD) were classified according to consensus criteria. The primary endpoint was overall survival (OS), and secondary endpoints included progression rate and non-relapse mortality (NRM). Cox proportional hazards regression analysis was used to evaluate predictors of OS, and Fine and Gray regression for predictors of relapse and NRM. Competing risks were accounted for in analyses pertaining to progression and NRM. Results: A total of 376 Ph neg ALL AYA patients were included in the analysis, 247 from MDACC and 129 from DFCI. The median age at transplant was 25 (range 15-40) years, 39 patients (10%) were aged ≤18 years at time of HCT and 251 (67%) were males.The majority had B-ALL (n=282, 75%), 42 (11%) had complex karyotype and 28 patients (7%) had translocation (4:11). Most patients received either pediatric-inspired (48%) or hyper- cyclophosphamide, vincristine sulfate, doxorubicin, dexamethasone (CVAD) based (42%) frontline induction regimens, and the median time from diagnosis to HCT was 11 (range 2-283) months. At transplant, most patients were in CR1 or CR2 (44% each); 63% of patients achieved MRD negativity prior to HCT. Most patients received an HCT from a matched unrelated donor (MUD) (33%) or a matched sibling donor (MSD) (32%), and most patients received myeloablative conditioning (MAC) (79%) ( Table 1). The cumulative incidence of grade 2-4 acute GvHD and grade 3-4 acute GvHD at 6 months was 37% (95% CI 33%-42%) and 13% (95% CI 10%-17%), respectively. The cumulative incidence of chronic GvHD at 3 years was 28% (95% CI 23%-33%), with most patients experiencing either mild (39%) or moderate (36%) chronic GvHD, and 25% had severe chronic GvHD. For patients transplanted in CR1, CR2 and CR3/PD the estimated 3-year OS was 69% (95% CI 61%-77%), 53% (95% CI 44%-61%) and 29% (95% CI 16%-43%), respectively; the 3-year NRM rate was 9% (95% CI 5%-15%), 18% (95% CI 13%-25%) and 27% (95% CI 16%-43%), respectively; and the 3-year progression rate was 27% (95% CI 20%-35%), 36% (95% CI 29%-45%) and 48% (95% CI 36%-65%), respectively. In multivariate analysis, HCT in CR3/PD was associated with inferior OS (HR 4.3, p<0.001) and higher NRM (HR 2.3, p=0.04, Table 2), however there was no difference in survival between HCT at CR1 vs. CR2 (p=0.3); >2 lines of therapy prior to HCT was associated with inferior OS (HR 1.8, p=0.004) and higher rate of progression (HR 1.9, p=0.008); HCT-CI>3 was associated with inferior OS (HR 1.6, p=0.01) and higher NRM (2.3, p=0.004); positive MRD status prior to HCT was associated with inferior OS (HR 1.9, p=0.004) and higher rate of progression (HR 3.3, p<0.001); use of bone marrow graft was associated with lower rate of progression (HR 0.6, p=0.02) and use of a matched donor (MSD/MUD) was associated with lower NRM (HR 0.5, p=0.01). Conclusions: In this analysis of a large dual-center cohort of AYA Ph -ALL patients that received HCT, we found that patients transplanted in CR1 had the most favorable outcomes with 69% 3-year OS. Patients not in CR1/CR2, patients who received HCT after >2 lines of therapy and those with positive MRD pre-HCT had inferior OS on MVA. Although patients who received HCT at CR3/PD had inferior OS, an estimated one-third of patients were still alive at 3 years after HCT.

Outcomes and Causes of Mortality in Polycythemia Vera in a Distinct Demographic: Adolescents and Young Adults

Background Polycythemia vera (PV) is an uncommon hematologic malignancy that occurs predominantly in older populations with an overall median age of 61 years, with less than 10% occurring below 40 years. 1 The adolescent and young adults (AYA) age group is defined as young people between 15 to 39 years of age. 2 There is a paucity of information on PV in AYA in the literature. We aimed to examine the outcomes and causes of death in PV in AYA and compare them with older people aged 40 years and above. Methods Cases of PV were identified from the Incidence-Surveillance, Epidemiology, and End-result (SEER) Research Plus Data, 17 Registries (2000 - 2020) using the International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3) code 9950. Only primary cases were included. Patients' characteristics (sex, race, and causes of death) were obtained from the database. Those without microscopic or laboratory diagnosis, unknown race, cause of death, or survival were excluded. Descriptive statistics (frequencies and median) were compared with the Chi-squared test between the AYA and older population. The Kaplan-Meier method was used to estimate median overall survival (OS). Cox regression analysis was done to determine predictors of survival in both age groups. Results We identified 10,696 patients with PV within our study period of 2000 - 2020. Out of these, only 7.8% (n=830) were in the AYA cohort compared to 92.2% of the patients aged ≥ 40 years. The median age was 33 years (IQR: 27 - 37) in AYA and 65 years (IQR: 55 - 75) in the older group. There were more males (70% vs. 55%, p<0.001) but a lower proportion of Whites (67% vs. 78%, p<0.001) in the AYA group than in the older group. As shown in Figure 1, the causes of death (COD) were similar between AYA and older patients except for myeloproliferative/myelodysplastic syndromes, which was more common in the older people compared to AYA (15.4% vs. 3.7%, p=0.018). Conversely, non-disease causes of death (accidents, adverse events, suicides/self-inflicted injuries etc) were more frequent in the AYA group than in the older group (16.7% vs. 4.4%, p=0.001). The five and 10-year overall survival (OS) were 97.0% and 93.4%, respectively, in the AYA, but 81.2% and 63.4%, respectively, in the older group. On multivariate analysis, as shown in Table 1, there was no association between sex, race, geographical location, and survival in the AYA cohort, except higher income status was associated with reduced odds of mortality. In the older group, male sex (HR=0.74, 95% CI: 0.69 - 0.80) and diagnosis of PV between 2011 - 2020 (HR=0.65, 95% CI: 0.60 - 0.71) were independent predictors of better survival outcomes. Non-Hispanic White (HR=1.36, 95% CI: 1.17 - 1.57) and Black races (HR=1.47, 95% CI: 1.21 - 1.79), and living in a non-metropolitan area (HR=1.12, 95% CI: 1.02 - 1.23) were associated with poor survival in the older group. Conclusion Polycythemia Vera, though rare in AYA, seems to have good survival outcomes in this group. We observed that compared to the older population, AYA were more likely to die from non-disease causes and less frequently from myeloproliferative/myelodysplastic syndromes. Improved income status appears to favor survival outcomes in AYA.

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.

Association of state policies modifying Supplemental Nutrition Assistance Program (SNAP) eligibility and cancer stage at diagnosis.

214 Background: Food insecurity is associated with access to care and is particularly prevalent among adolescents and young adults (AYA) with cancer. The Supplemental Nutrition Assistance Program (SNAP) was designed to minimize food insecurity for low-income households. Under the broad-based categorial eligibility (BBCE) policy, states were given the ability to relax requirements for qualifying for SNAP through increasing the income limit or eliminating the asset test. While most SNAP policy changes under the BBCE policy occurred from 2009-2011, it is unknown whether these policies affect access to care among AYA with cancer. We sought to determine whether state SNAP eligibility policies were associated with stage at diagnosis among AYA patients. Methods: We utilized the Surveillance, Epidemiology, and End Results database to obtain data from 2006-2019 for newly diagnosed patients with cancer ages 18-39 years from 11 states. All cancer types were included with the exception of liquid tumors and other unstaged cancers. Difference-in-differences analyses were utilized to evaluate changes in the percentage of localized and distant stage diagnoses from pre- to post-policy enactment between states that enacted (1) asset test elimination or (2) increased income limit policies. Linear probability models were adjusted for state and year fixed effects, race, ethnicity, sex, metropolitan residence, marital status, county-level income, cancer type, and Medicaid expansion effects. We also accounted for state-level clustering via clustered standard errors. Event study analyses were utilized to assess the plausibility of the parallel trends assumption. Results: A total of 157,380 AYAs with cancer were identified. In adjusted difference-in-differences analyses, there was a 0.67 percentage point (PP) (95% CI = 0.15 to 1.19, P=.012) increase in localized stage cancer diagnoses and a -0.81 PP (95% CI = -1.41 to -0.21, P=.008) decrease in distant stage cancer diagnoses in states with increased income limits for SNAP eligibility relative to other states. There were no statistically significant changes in the percentage of localized (0.87 PP, 95% CI = -1.27 to 3.00, P=.43) or distant (0.05 PP, 95% CI = -1.44 to 1.55, P=.94) stage cancers with policies eliminating the asset test. Among patients with cervical cancer, where screening is recommended in this age group, there were extremely similar patterns. Conclusions: State policies increasing income eligibility limits for the Supplemental Nutrition Assistance Program were associated with a higher percentage of localized stage and a lower percentage of distant stage cancers among adolescents and young adults. These data add to a growing body of literature suggesting that policies that address social determinants of health may improve access to care.

Comprehensive cancer-related resources for adolescents and young adults (AYAs) treated in the community setting: 2022 Landscape survey results.

151 Background: Availability of guideline-endorsed, cancer-related resources for adolescents and young adults (AYAs: aged 15–39) with cancer is unknown. AYAs often receive treatment in community settings. We describe the current landscape of comprehensive cancer care resources for AYAs treated in community settings. Methods: NCI Community Oncology Research Program (NCORP) practice groups completed the Landscape Assessment in 2022 to describe available infrastructure, resources, and research capacity. Practice groups were included in this analysis if ≥10% of their annual cancer cases were within the AYA age range, or at least 50 AYA cancer cases are treated annually. We described the proportion of practices serving AYA patients with access to fertility preservation, mental health services, genetic testing and counseling, nutritional counseling, distress monitoring (psychosocial and financial), palliative care, and survivorship programs. Results: Of 271 responding practice groups, 77 (28%) met criteria for treating AYAs, whereas 102 (38%) did not meet criteria. The remaining 92 (34%) could not be classified due to missing data. Among the 77 practices treating AYAs, fertility preservation was available at 51% (oocyte cryopreservation) and 58% (sperm banking) of practices. While nutritional support and genetic testing were widely available (99% and 100% respectively), only 49% of practices treating AYAs offered survivorship programs (Table 1). Conclusions: Many AYAs receiving treatment in community settings lack access to key resources for cancer care, including fertility preservation and survivorship services. Future research should seek to identify barriers and facilitators to offering comprehensive resources in NCORP practices that serve AYAs and to advance understanding of AYA uptake of available resources.[Table: see text]

Future of Treatment of Adolescents and Young Adults With ALL: A Vision for Collaboration and Equity.

Over the past several decades, survival of children with ALL has improved dramatically with treatment regimens refined through cooperative group trials. Despite aggressive treatment and iterative therapy changes for adolescents and young adults (AYAs), improvement has not been as promising. Comparisons between pediatric and adult clinical trials have consistently demonstrated superior outcomes for AYAs treated on pediatric ALL protocols, leading to the implementation of pediatric-inspired ALL protocols by several groups worldwide and/or expansion of the age limit of pediatric trials to include the full spectrum of the AYA population. Despite these efforts, AYAs in both pediatric and adult settings continue to have inferior survival compared with younger children with ALL. Real-world data suggest that uptake of pediatric-style treatment is variable, and even with identical pediatric-style treatment, AYAs still fare worse than younger children. As we enter an era of immunotherapy and precision medicine for newly diagnosed ALL, now is an opportune time to consider how best to approach future therapy for AYA patients. Comparisons of pediatric and adult treatment approaches and subanalyses of AYA patients will help guide harmonization of treatment. The focus of the next stage of ALL therapy for AYA should not only involve novel treatment approaches but also standardization and optimization of supportive care measures, psychosocial support, adherence interventions, oncofertility treatment, and survivorship care. All these efforts should simultaneously work to address health disparities to ensure that a future of improved outcomes is experienced equitably for all AYA patients.

Improving Supportive and Palliative Care Integration in Adolescent and Young Adult Cancer.

Purpose: Timely supportive and palliative care (SPC) integration in adolescent and young adult (AYA) cancer management is recommended in curative and palliative settings. However, multiple barriers exist to implementing this goal. Liverpool Cancer Therapy Center (LCTC) serviced a growing AYA (15-39 years) population without AYA-dedicated services and the vast majority receiving no SPC engagement. Concerned this was placing AYA patients' wellbeing at risk, we determined a cultural change was required and that the newly established AYA Supportive and Palliative Care (AYASPC) Service could facilitate this. Methods: The AYASPC Service conducted a 6-month quality improvement project aiming to increase its referrals from a baseline average of one per month to four per month, to increase confidence in making SPC referrals and to enhance appreciation for specialized AYA care. Interventions included formalizing an AYASPC referral pathway with broad indications, and educating clinicians on holistic AYA care, the AYASPC Service's model of care (MoC) and AYASPC referral benefits. Results: During the project, 27 AYASPC referrals were made. Referrals consistently exceeded the Service's baseline, and from 3 months onward exceeded the project target. Additionally, referrals were made earlier (29.6% at diagnosis), for a variety of cancer diagnoses with varied prognoses, and for indications beyond traditional issues of complex symptoms and end-of-life care. Clinicians also expressed greater confidence in supporting AYAs and making SPC referrals. Conclusion: In a brief timeframe, the AYASPC Service's innovative and adaptable MoC and project interventions sustainably improved AYASPC access and affected a positive cultural shift around AYA care and advocacy.

Nonbiological factors affecting outcomes in adolescents and young adults with lymphoma.

The impact of nonbiological factors (NBF) on survival was investigated in a large cohort of adolescents and young adults (AYA) with lymphoma in the United States (US). We found that uninsured and Medicaid AYA beneficiaries with classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma (NHL) are at significantly increased risk of death when compared with their insured counterpart even after adjustment for other factors affecting survival. Increased risk of death was also noted for Non-Hispanic Black (NHB) patients with cHL and NHL when compared to Non-Hispanic White (NHW) patients, however, only Hispanic patients with NHL were found to have a significantly increased mortality risk while those with cHL were not. NHL AYA patients residing in lower-income counties are at increased risk of death. The strong association of NBF with survival indicates opportunities to improve the survival of AYA lymphoma patients by improving access/quality of care in the US.

Impact of Consolidative Radiation on Overall and Progression-Free Survival in Pediatric, Adolescent, and Young Adult Metastatic Bone and Soft Tissue Sarcoma

To determine the association between consolidative radiation (RT) and survival in children, adolescents, and young adults with metastatic sarcoma. Eligibility criteria included patients aged ≤39 years with newly diagnosed metastatic bone or soft tissue sarcoma who completed local control of the primary tumor without disease progression. Consolidative RT was defined as RT to all known sites of metastatic disease. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). The least absolute shrinkage and selection operator Cox provided adjusted estimates. To account for immortal time bias, consolidative RT was used as a time-varying covariate in a time dependent Cox model. Distant failure was estimated using the Fine-Gray model. Patients (n=85) had a median age at diagnosis of 14.8 years. Most common histology was Ewing Sarcoma (45.9%) followed by rhabdomyosarcoma (40.0%). Receipt of consolidative RT was associated with Ewing Sarcoma (P < .001) and local control modality as those who underwent local control with surgery and RT compared with surgery alone were more likely to be treated with consolidative RT (P=.034). Consolidative RT was independently associated with improved OS (hazard ratio [HR], 0.41; 95% CI, 0.17-0.98; P=.045) and improved PFS (HR, 0.37; 95% CI, 0.16-0.88; P=.024) after adjusting for confounding variables and immortal time bias. Patients treated with consolidative RT also experienced a lower risk of distant failure (HR, 0.33; 95% CI, 0.17-0.64; P=.001). In an independent data set of patients with metachronous progression (n=36), consolidative RT remained independently associated with improved OS. Consolidative RT was independently associated with improved OS and PFS and decreased risk of distant failure in child, adolescent, and young adult patients with metastatic sarcoma. Future work should evaluate biomarkers to optimize patient selection, timing, and dose for consolidative RT.

The pathobiology of select adolescent young adult lymphomas.

Lymphoid cancers are among the most frequent cancers diagnosed in adolescents and young adults (AYA), ranging from approximately 30%-35% of cancer diagnoses in adolescent patients (age 10-19) to approximately 10% in patients aged 30-39 years. Moreover, the specific distribution of lymphoid cancer types varies by age with substantial shifts in the subtype distributions between pediatric, AYA, adult, and older adult patients. Currently, biology studies specific to AYA lymphomas are rare and therefore insight into age-related pathogenesis is incomplete. This review focuses on the paradigmatic epidemiology and pathogenesis of select lymphomas, occurring in the AYA patient population. With the example of posttransplant lymphoproliferative disorders, nodular lymphocyte-predominant Hodgkin lymphoma, follicular lymphoma (incl. pediatric-type follicular lymphoma), and mediastinal lymphomas (incl. classic Hodgkin lymphoma, primary mediastinal large B cell lymphoma and mediastinal gray zone lymphoma), we here illustrate the current state-of-the-art in lymphoma classification, recent molecular insights including genomics, and translational opportunities. To improve outcome and quality of life, international collaboration in consortia dedicated to AYA lymphoma is needed to overcome challenges related to siloed biospecimens and data collections as well as to develop studies designed specifically for this unique population.

Clinical Outcomes in AYAs (Adolescents and Young Adults) Treated with Proton Therapy for Uveal Melanoma: A Comparative Matching Study with Elder Adults.

The aim of this study was to compare the clinical outcomes of adolescents and young adults (AYAs) with those of elder adult patients treated with proton therapy (PT) for uveal melanoma (UM). A retrospective, comparative study was conducted in UM patients who underwent PT at the Ocular Oncology Unit of the Jules-Gonin Eye Hospital (University of Lausanne, Lausanne, Switzerland) and the Paul Scherrer Institute (PSI); (Villigen, Switzerland) between January 1997 and December 2007. Propensity score matching (PSM) was used to select for each AYA (between 15-39 years old) an elder adult patient (≥40 years) with similar characteristics. We assessed ocular follow-up, local tumor control, metastasis incidence, and overall and relative survival (OS and RS). Non-terminal outcomes were then compared between the two groups using competing risk survival analysis. Out of a total of 2261 consecutive UM patients, after excluding 4 children (<15 years) and 6 patients who were metastatic at presentation, we identified 272 AYA patients and matched 270 of them with 270 elder adult patients. Before PSM, the AYA patients had a higher incidence of primary iris melanoma (4.0% vs. 1.4%; p = 0.005), while the elder patients were more likely to have other neoplastic diseases at presentation (9% vs. 3.7%; p = 0.004). Ocular outcomes and local tumor control were similar in both groups. Cumulative metastasis incidence for the AYA and elder adult groups was 13% and 7.9% at 5 years and 19.7% and 12.7% at 10 years, respectively, which was not significantly different between the groups (p = 0.214). The OS was similar in the two groups (p = 0.602), with estimates in the AYA and elder adult groups of 95.5% and 96.6% at 5 years and 94.6% and 91.4% at 10 years, respectively. However, the relative survival (RS) estimation was worse in the AYA group than the elder group (p = 0.036). While AYAs treated with PT for UM have similar ocular outcomes and present the same metastasis incidence and OS as elder adults, their RS is worse than that in elder adults, when compared with the population in general.

Acute HIV Diagnosis After Initiation of Pre-exposure Prophylaxis in a Young Adult Patient: A Case Report

Oral pre-exposure prophylaxis (PrEP) in the prevention of human immunodeficiency virus (HIV) infection is highly effective, yet the majority of sexually active adolescents and young adults (AYAs) at highest risk for HIV infection, particularly AYA males who have sex with males, have not been prescribed this medication. Provider hesitancy in prescribing PrEP to at-risk AYA patients is often associated with concerns about patient nonadherence and its effect on inducing HIV medication resistance. This case report has two aims. First, to outline the clinical course for an AYA patient prescribed PrEP for 3 months and then found to have HIV with an M184V resistance mutation and subsequently started on HIV treatment. And second, to illustrate how the benefits of PrEP initiation outweigh its risks by presenting clinical data on resistance patterns to PrEP medications. The patient eventually achieved viral suppression within 5 months of starting HIV treatment which has been sustained up to 2 years. This case illustrates that M184V resistance mutations, although rarely associated with PrEP, are unlikely to impact options for HIV treatment. Providers should recommend and prescribe oral PrEP to AYA patients at risk for HIV infection without concern for nonadherence leading to HIV medication resistance.

Special Considerations of Pelvic Radiation Therapy in the Adolescent and Young Adult (AYA) Female Population

Abstract Adolescent and young adult (AYA) patients are a small, but very important, group of cancer patients to focus on because they have historically been underrepresented in clinical trials and they have unique care needs that, if unaddressed, lead to poorer long-term survival outcomes and quality of life. Pelvic radiation therapy (RT) is frequently utilized in treatment paradigms for pelvic cancers, and treatment can lead to several acute and late side effects in patients. Some of these side effects can be especially impactful in AYA female cancer patients, including issues surrounding fertility and premature ovarian insufficiency, sexual health, financial toxicity, and psychological impact on body image, relationships, and other facets of a young person’s life. An understanding of how pelvic RT can specifically affect AYA patients can help radiation oncologists to better counsel patients and take proactive steps to help mitigate side effects, as well as make referrals to other specialists who are equipped with resources that may help improve the AYA patient’s long-term quality of life and survivorship.