Adolescents And Young Adults Group Research Articles

Genomic alteration in sporadic adolescent and young adult-onset colorectal adenocarcinoma.

154 Background: Colorectal cancer (CRC) incidence is increasing in adults younger than 50 years. This study evaluated genomic alteration in adolescent and young adult (AYA)-onset sporadic CRC patients who aged between 15 and 39 years. Methods: DNA from 90 archived formalin-fixed, paraffin-embedded (FFPE) tissue samples that histologically confirmed adenocarcinoma with proficient mismatch repair tumors at Siriraj Hospital (Bangkok, Thailand) were extracted. Patients who clinically suspected familial adenomatous polyposis were excluded. Gene mutational analysis was performed by next-generation sequencing (NGS) using an Oncomine Comprehensive Assay Plus kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA) and compared with previous reported molecular data in adult-onset CRC from our group. Results: The top 5 mutations frequency observed were TP53, KRAS, FBXW7, PIK3CA, and SMAD4 mutations which were comparable to what reported in adult-onset CRC. However, FBXW7, PIK3CA, NOTCH1, FGFR3, ERBB2, and PTEN were reported more frequent in AYA group. No difference in number of KRAS, NRAS, and BRAF mutations among 2 groups. Table below shows key cancer genes mutation frequencies. Conclusions: This study is the comprehensive report hotspot mutations using NGS in sporadic AYA-onset sporadic CRC patients. The most commonly identified gene mutation frequencies among AYA-onset were similar to those reported in adult-onset, except for FBXW7, PIK3CA, NOTCH1, FGFR3, ERBB2, and PTEN mutations that had a slightly higher frequency. Further studies on larger sample set for genetic and epigenetic landscape are required. [Table: see text]

Histopathological Spectrum of Central Nervous System Tumours in Adolescent and Young Adults: A Cross-sectional Study from Punjab, Northern India

Introduction: Central Nervous System (CNS) tumours are a common cause of cancer-related deaths in adolescents and young adults. The challenges in diagnosing and treating CNS tumours in this age group are unique and require special attention. Aim: To study the histopathological spectrum of CNS tumours in Adolescents and Young Adults (AYA). Materials and Methods: Present five-year cross-sectional study was conducted on CNS biopsies received in the Department of Pathology at Dayanand Medical College and Hospital, Ludhiana, Punjab, India, from July 1, 2016, to June 30, 2021, to analyse the histopathological spectrum of CNS tumours in the AYA group based on the site of the lesion, age, gender, and Isocitrate Dehydrogenase (IDH) status. Results: During the study period, a total of 215 cases of CNS tumours were identified, of which 52 (24.2%) belonged to the AYA group. Of these, 35 (67.3%) were males and 17 (32.7%) were females. The majority of the patients presented with complaints of headache (50/52, 96.1%), with the frontal lobe being the most common site of involvement (21/52, 40.4%). Diffuse astrocytic and oligodendroglial tumours were the most commonly observed (23/52, 44.2%). Conclusion: CNS tumours are one of the most common cancer diagnosis among the AYA group, and awareness should be enhanced among histopathologists and oncologists regarding these tumours based on the updated classification.

Racial Disparities in the Incidence and Survival Outcomes in Diffuse Large B-Cell Lymphoma in Adolescents and Young Adults

Background Diffuse Large B-Cell Lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma, and generally occurs most frequently in Whites, with a median age of 64 years 1. Adolescent and Young Adult (AYA) cancer is defined as cancer in individuals 15 to 39 years old 2. There is paucity of data on racial and ethnic disparities in the incidence of DLBCL in AYA. We aim to determine the influence of race on the incidence and survival outcomes of DLBCL in the AYA cohort. Methods Data from the Surveillance, Epidemiology, and End Results (SEER) 17 Research Plus database program was utilized to obtain the annual percentage change (APC) in incidence of DLBCL from 2000 - 2020 for patients aged 15 - 39 years (AYA group). Patient characteristics were expressed in proportions (%). The Kaplan Meier method was used to determine overall survival (OS) and cancer-specific survival (CSS). Cox regression was performed to determine predictors of survival. A p-value ≤0.05 was considered statistically significant. Results We identified a total of 8735 AYA patients diagnosed with DLBCL (see Table). The proportion of patients with DLBCL decreased the most in Non Hispanic Blacks (NHB, 45% vs 55%, p-value ≤0.001) and Non-Hispanic Whites (NHW, 45% vs 55%, p-value ≤0.001), followed by Non-Hispanic American Indian/Alaska Natives (NHAIAN, 48% vs 52%, p-value ≤0.001). No change was noted in the Hispanic (all races) group (50% vs 50%, p-value ≤0.001). The Non-Hispanic Asian/Pacific Islander (NHAPI) group showed the highest proportion of patients with DLBCL (58%) in 2011-2020 compared to 2000-2010 (42%), p-value ≤0.001. Over the study period (2000 - 2020), there was a significant decrease in the yearly incidence of DLBCL in the overall AYA cohort (APC: -0.5%, p <0.05). This reduction was most pronounced in NHB (APC: -1.4%, p-value ≤0.001), followed by Hispanics, all races (APC: -0.65%, p-value ≤0.001) and NHW (-0.57%, p ≤0.04). However, there was a significant increase in the incidence of DLBCL in NHAPI (APC: 1.88%, p-value ≤0.001) during the same time period. OS for NHAIAN was 58 months (95% CI: 21-147, p ≤0.001), 63 months (95% CI: 19-139, p-value ≤0.001) for NHAPI; 63 months (95% CI: 13-142, p ≤0.001) for NHB; 58 months (95% CI 14-134, p≤0.001) for Hispanics, all races; and 98 months (95% CI: 31-172, p≤0.001) for NHW. The 5 and 10-year CSS were 86.5% and 85.4% for NHW (p-value ≤0.001); 85.4% and 84.4% for NHAPI (p ≤0.001); 81.3% and 80.3% for Hispanics, all races (p ≤0.001); 68.1% and 68.1% (p ≤0.001) for NHAIAN; and 71.9% and 69.4% for NHB (p-value ≤0.001) (see Figure).In the multivariable model, NHB (HR = 1.91, 95%, CI: 1.70-2.15, p ≤0.001), NHAIAN (HR = 2.09, 95% CI: 1.29-3.38, p≤0.003) and Hispanic, all races (HR 1.35, 95% CI: 1.20-1.53, p≤0.001) were associated with reduced odds of survival, compared to NHW. Conclusion There is a significant racial/ethnic disparity in the incidence and outcomes of DLBCL among AYA patients. Increase in incidence of DLBCL was observed only in NHAPI. Despite the significant improvement in the incidence of DLBCL in NHB over the years, odds of survival remain poorer than other racial/ethnic groups, except NHAIAN. More studies are needed to explore the reasons for these racial differences and more concerted efforts are needed to improve outcomes among AYA patients.

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<0.001, Figure 1). The age group comparison also found more proportion of males in AYA vs olders (66.1% vs 58.5%, p<0.001), more proportion of non-white patients in AYA group (29.6% vs 15.3%, p<0.001) and that AYA patients were more prone to receive chemotherapy (32.7% vs 14.8%, p<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 <$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<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.

Risk-Adjusted Therapies Yield Equivalent Outcomes for Adolescents and Young Adults (AYAs) Treated for Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL) on Children's Oncology Group (COG) Studies AALL0434 and AALL1231

Introduction Previous clinical trials have reported that adolescent and young adult (AYA) patients treated for T-cell acute lymphoblastic leukemia (T-ALL) have lower disease-free survival (DFS) and overall survival (OS) and increased toxicity as compared to younger patients. Results for the AYA cohort treated on two COG international phase 3 trials for T-ALL are reported here. Patients and Methods AALL0434 enrolled 1562 T-ALL patients (2007-2014) and AALL1231 enrolled 615 T-ALL patients (2014-2019) treated on augmented BFM (ABFM) regimens. AYA patients were defined as age ≥16 years of age (AALL0434: n=226; AALL1231: n = 107). Both studies allowed enrollment up to age 31 years. On AALL0434, participants were randomized to receive escalating dose methotrexate (CMTX) without leucovorin rescue + pegaspargase or high dose MTX (HDMTX) + leucovorin rescue. Intermediate and high-risk patients were randomized to receive or not receive six 5-day courses of nelarabine (Nel). Risk group assignments in AYA vs non-AYA patients can be found in Table 1. On AALL1231, participants were randomized to receive or not receive bortezomib in Induction and Delayed Intensification. Key differences between AALL0434 and AALL1231 ABFM backbones included the use of prednisone in induction in AALL0434 versus dexamethasone in AALL1231, and cranial radiation therapy in the majority of AALL0434 participants versus only in patients with central nervous system involvement in AALL1231. Results On AALL0434, the 4-year DFS for AYA was 81% compared to 84% for those <16 years old (P=0.5965), and OS was 88% and 90% respectively (P=0.3478). AYA patients randomized to CMTX (n=70) had a superior DFS compared to those randomized to HDMTX (n=72) with 4-year DFS 96% versus 78% respectively (P=0.0038). No disadvantage was seen among AYA subjects who received nelarabine versus those who did not, as shown by a 4-year DFS 85% versus 89%, respectively (N=54) (P=0.8116), albeit the sample size was small. On AALL1231, the 4-year EFS for AYA (n=107) was 82.7±3.9% compared to 82.2 ±1.7% for non-AYA (n=508) (P=0.727), and OS was 86.5 ±3.5% and 88.4 ±1.5% respectively (P=0.553). No difference in outcome was seen for AYA patients randomized to receive/not receive bortezomib. Combined outcome data for AALL0434 and AAL1231 demonstrates 4-year EFS for AYA (n=333) of 82.2+2.4% vs 83.9+0.9% for non-AYA (n=1844) (P=0.52) (Figure 1) and OS of 87.5+2.1% vs 90+0.8% respectively (P=0.19). Significant differences in patient characteristics in AALL0434 were higher initial white blood counts (P=0.0004) and higher risk group category (P=0.0002) for AYA patients. There were no significant differences in the AALL0434 AYA cohort compared to younger patients in CNS disease status, race, ethnicity, remission status at end of induction, or day 29 end of induction minimal residual disease (MRD). Toxicity rates were not significantly different in non-AYA vs AYA patients with the exception of upper respiratory infection (9.4% vs 1.8%; P=0.0001) and osteonecrosis (4.8% vs 17.7%; P<0.0001) in AALL0434. Rates of sepsis, catheter-related infection, and other infections were not significantly different between AYA and younger patients in AALL0434. Analysis of patient characteristics and toxicity rates in AALL1231, as well as analysis of the combined toxicity data for AALL0434 and AAL1231, are currently underway and will be presented at the meeting. Conclusion COG AALL0434 and AALL1231 show outstanding overall outcomes for AYA patients with no significant difference in survival between AYA and non-AYA patients on either study, despite differences in the ABFM backbones and the higher risk features seen among the AYA group in AALL0434. There were similar occurrences of therapy-related toxicities for AYA and non-AYA study participants on AALL0434. Despite small numbers, CMTX holds a survival advantage for AYA T-ALL patients, with no survival disadvantage seen among AYA T-ALL patients who received Nel. Bortezomib does not offer significant benefit for AYA T-ALL patients.

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)

To Study Outcomes in Young CML Treated with TKI. a Registry Data from Hematological Cancer Consortium (HCC) of India

Background: Chronic Myeloid Leukemia (CML) is a hematological malignancy characterized by the abnormal proliferation of white blood cells. While CML is primarily a disease of middle and old age, a significant proportion of cases are diagnosed in adolescents and young adults. The incidence of CML in India is relatively low (0.53 to 0.71 / 100,000), but the country's large population means that even a small increase in incidence can translate to a significant disease burden. The prognosis of CML has improved dramatically with the advent of tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, and nilotinib, which have transformed CML from a fatal disease to a chronic, manageable condition. However, the optimal management of CML in adolescents and young adults (AYA) is still a matter of debate, and there is limited data on the outcome of this disease in this age group in India. Hematology Cancer Consortium (HCC) is a group of premier hematology and oncology institutes from India created for collecting and collating data of various hematologic malignancies in a central online data management system. Design and methods: Retrospective data from 01 Jan 2020 to 01 June 2022, of all CML patients treated with TKI at 11 member institutions of HCC were analysed. The cohort was divided into AYA (15 to 29 years) and others ( 30 years or more). The objective of this study was to determine the disease outcome of adolescents and young adults (AYA) with CML in India as measured by event free survival (EFS), overall survival (OS) and transformation free survival (TFS) . Events were defined as death from any cause, progression to accelerated phase (AP) or blast crisis (BC) and change to second generation TKI from imatinib while on therapy. We also compared the outcome of AYA with others. Results: Total of 1070 patients diagnosed with CML were included in the study. The patients of age group 15-29 years were 273/1070 (25.5%). Most were in chronic phase (249/273, 95.04%). The low-risk CML cases by Sokal score were 61 (26.75%) cases in 15-29 years age group in comparison to 69 (11.11%) cases in the older group and the difference was statistically significant (p<0.001).Low-risk cases by ELTS and EUTO score were seen in 32.51% and 61.30% cases in 15-29 years age group and it was comparable to other group (24.9 % and 62.1%). The type of transcript were P210 in 202 (97.58%) cases in AYA group. Spleen size, hemoglobin, WBC, Platelet, blasts (%), quantitative BCR ABL (%) were comparable in both the groups. Imatinib was used as first TKI in 193 (71.75%) cases. Significantly more number of patients in AYA group were treated upfront with second generation TKI (28.2%) in comparison to others (23.3%) (p= 0.02). The median doses missed by patients in 15-29 years group during first 03 months were 5, while in other group it was 13 and it was statistically significant (p=0.002). Median duration of therapy was 13 (0-28) months in AYA and 12 (0-38) months in other group. Progression to blast crisis was seen in 3/273 (0.01%) patients in the AYA group. While OS and transformation free survival were comparable in both groups, event free survival (EFS) was significantly better in AYA group (Fig-1A-B). Conclusion: While the AYA group had a significantly less low risk cases by Sokal score, more numbers were treated upfront with second generation TKI. EFS was significantly better in AYA group. Major shortcoming of this registry data is short follow up duration and very less number of evaluable patients for assessing molecular and cytogenetic response.

Chronic Myeloid Leukemia in Adolescents and Young Adults: A SEER-Based Analysis of Characteristics and Survival Outcomes of 1565 Patients

Introduction: Adolescents and Young Adults (AYA) are individuals between 15-39 years old. There are an estimated 1 million new cases of cancers in this age group yearly [1]. Although Chronic Myeloid Leukemia (CML) is typically a disease of middle-aged and elder patients, with a median age of 62 years [1], AYA accounts for about 22.1% of all CML cases [2]. There has been little focus directed towards this age group and most studies focus on the middle-aged and elderly. Despite the remarkable improvement in the survival of CML over the years, the largest study to date [3] suggested poor survival outcomes for patients in underserved populations and with low income. We aimed to determine whether sociodemographic differences exist in the AYA age group. Method: The Surveillance, Epidemiology, and End-Result (SEER) registry research plus database 17 (2000 -2020) was used to assess and compare the survival outcomes in the AYA group and older population diagnosed with CML. Both univariate and multivariate analyses were performed. Cox proportional hazards regression was used to determine prognostic factors for survival. A two-sided p-value ≤0.05 was considered significant. Results: A total of 6,319 patients with CML were identified, of which 75.2% (n= 4754) were adults ≥40 years, and 24.8% (n= 1565) were AYAs . Amongst the AYA, 51.4% (n=804) were Non-Hispanic White (NHW), 25 % (n=390) were Hispanics, 12.1% (n=189) were Non-Hispanic Black (NHB), 10.5% (n=164) were Non-Hispanic Asian or Pacific Islander (NHAPI) and 1.2% (n=18) were Non-Hispanic American Indian/Alaska Native (NHAIA) [Table 1]. The frequency of Hispanics in the AYA group was more compared to adults ≥40 years (25% vs 12.9%). NHWs had a lower frequency in the AYA group compared to adults ≥40 years (51.4% vs 67.5%) and NHBs had a similar distribution in both age groups (12.1% vs 11.6%). The proportion of mortality attributed to CML was lower in the AYA group compared to older adults ≥40 years (7.7% vs 11.9%). The results for individual Cox regression for each racial group show that AYA Hispanic males had a worse prognosis than females (HR= 2.930, 95% CI: 1.234-6.960), such observation was not seen in other AYA races [Table 2] but it was seen in Hispanic adult males ≥40 years (HR= 1.583, 95% CI: 1.074-2.334). Also, we identified that for patients aged ≥40 years, male sex was an independent poor prognostic factor for NHW (HR= 1.259, 95% CI: 1.074-1.476) and NWB (HR=1.879, 95% CI: 1.232-2.864) [Table 2]. Conclusion: Our study shows similar demographic characteristics between AYA and adults ≥40 years old. However, AYAs are less likely to die from CML compared to adults ≥40 years. Hispanic males appear to have a worse outcome than females, an observation seen in both age groups, and is independent of other analyzed prognostic factors. More research is needed to examine and identify other prognostic factors of CML in AYA with the aim of improving their survival outcomes.

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.

Clinical prognosis and related molecular features of hepatitis B-associated adolescent and young adult hepatocellular carcinoma

BackgroundInattention has been given to the pathogenesis of adolescent and young adult (AYA) hepatocellular carcinoma (HCC). Due to the more advanced tumor progression and poorer prognosis of AYA-HCC, together with a better tolerance ability, noncirrhotic background, and a stronger willingness to treat AYA-HCC, clinical and molecular biology studies are urgent and necessary, especially for those with hepatitis B infection.MethodsFor clinical aspects, the overall survival, the recurrence-free survival, and the Cox analyses were performed. Then, functional analysis, gene clustering, metabolic-related analysis, immune infiltration and competing endogenous RNA (ceRNA) construction were carried out using whole transcriptome sequencing technique.ResultsBased on the clinical information of our HCC cohort, the overall survival and recurrence-free survival rates were worse in the AYA group than in the elderly group as previously described. According to our whole transcriptome sequencing results, functional analysis revealed that metabolism-related pathways as well as protein translation and endoplasmic reticulum processing were enriched. Then the hub metabolism-related genes were screened by metabolite–protein interactions (MPIs) and protein–protein interactions (PPIs). Fatty acid metabolism is a crucial component of metabolic pathways, abnormalities of which may be the reason for the worse prognosis of HBV-AYA HCC. Finally, the relationship of disrupted expression of metabolism-related genes with immune infiltration was also analyzed, and the lncRNA‒miRNA‒mRNA-related ceRNA network for HBV-AYA HCC was constructed, which may provide new cues for HBV-AHA HCC prevention.ConclusionThe worse prognosis and recurrence rate of HBV-AYA HCC may be related to abnormalities in metabolism-related pathways, especially disorders of fatty acid metabolism.

Acute Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The Good, the Bad, and the Ugly of Isolated Extramedullary Relapse in a Latin American Population

Hematopoietic stem cell transplantation (HSCT) is an effective therapy for acute leukemia (AL). Relapse represents the main cause of mortality. Isolated extramedullary relapse (iEMR) is atypical and has been related to better outcomes. Here we describe the clinical characteristics and outcomes of AL relapse after HSCT in our study population and analyze the impacts of different types of relapse on survival outcomes. This retrospective, multicenter study included 124 patients age ≥15 years with AL who underwent HSCT between 2004 and 2019. At diagnosis, 66.1% of the patients had lymphocytic AL, 19.7% presented with high-risk features, and 18.5% had extramedullary disease (EMD). At HSCT, 83.1% of the patients were in complete remission (CR), and 44.8% had negative measurable residual disease (MRD). The vast majority of donors were related (96%), including 48.4% HLA-matched and 47.6% haploidentical. Myeloablative conditioning was provided to 80.6% of patients. The median overall survival (OS) was 15 months (95% confidence interval [CI] 9.9 to 20.1 months). Factors associated with improved OS were adolescent and young adult (AYA) patient (P = .035), first or second CR (P = .026), and chronic graft-versus-host disease (GVHD) (P < .001). Acute GVHD grade III-IV (P = .009) was associated with increased mortality. The median relapse-free survival was 13 months (95% CI, 7.17 to 18.8 months); early disease status (P = .017) and chronic GVHD (P < .001) had protective roles. Sixty-eight patients (55%) relapsed after HSCT, with a median time to relapse of 6 months (95% CI, 3.6 to 8.4 months). iEMR was reported in 16 patients (23.5%). The most commonly involved extramedullary sites were the central nervous system and skin.Compared to patients with bone marrow relapse, all patients with iEMR had a diagnosis of acute lymphoid leukemia (P = .008), and 93.8% belonged to the AYA group; regarding pre-HSCT characteristics, iEMR patients had higher rates of negative MRD (P = .06) and a history of EMD (P = .009). Seventy-seven percent of relapsed patients received additional treatment with curative intent. The median OS after relapse (OSr) was 4 months (95% CI, 2.6 to 5.4 months). Factors related to increased OSr included lymphoid phenotype (P = .03), iEMR (P = .0042), late relapse (≥6 months) (P = .014), receipt of systemic therapy including second HSCT (P < .001), and response to therapy (P < .001). Rates of relapse and iEMR were higher than those previously reported in other studies. Advanced disease, reduced-intensity conditioning, and a diminished graft-versus-leukemia effect were factors influencing these findings. At relapse, presenting with iEMR, after 6 months, and receiving intensive therapy with adequate response were associated with better outcomes. Our results strongly suggest that a personalized approach to treating patients with HSCT is needed to counterbalance specific adverse factors and can positively impact clinical outcomes.

Abstract P4-06-06: Neoadjuvant B27 protocol in Triple-Negative Breast Cancer: Evaluation response rate, pathological complete response rates,toxicity,and the prognosis of Adolescent and Young Adult (AYA) age group compared to older population

Abstract Background: Neoadjuvant chemotherapy (NACT) is the standard early-stage triple-negative breast cancer (TNBC) treatment. Achieving pathological complete response (pCR) is considered an essential prognostic factor with favorable long-term outcomes. Younger patients have with poorer prognosis in breast cancer. To date, few studies are comparing the prognosis of AYA and older women (≥40) with breast cancer subtypes, specifically Triple-negative breast cancer (TNBC), as AYAs had higher proportions of this subtype. Method: Retrospective review was performed on female patients who received NACT at a King Hussien Cancer Center from January 2014 to June 2020. Data were collected from patients’ electronic medical records. TNBC was histopathologically confirmed. Logistic regression analysis of predictors of pathologic complete response (pCR). Survival curves were estimated with the Kaplan-Meier method. Multivariate analysis for EFS was performed using Cox’s proportional hazards regression model, covariates included age at diagnosis (AYA vs. ≥40), tumor size, nodal status LVI and pCR Result: We analyzed 211 women with stage I-III TNBC, including 62 (29.4%) women aged 18 to 39 years (AYA) and 149 (70.6%) ≥40 years. 138 (68.3%) were node positive, and 71 (34.8%) were T3/4 disease. Median follow-up was 28.1 months, median number of ER visit during NAC is 1 (0-11), 23 (10.9 %) patients had admission during neoadjuvant chemotherapy, most commonly due to febrile neutropenia 13 (56.9%). 37 (17.5%) patients did not complete NAC, due to disease progression in 22 (10.4%), and toxicity in 15 (7.1%) patients. 195 (92.4%) patients had surgery, including 75 (35.5%) had breast-conserving surgery (BCS). 166 (76.3%) patients had objective response, and 64 (30.3%) had pCR. 170 (80.6%) received adjuvant radiotherapy, and 38 (18%) received adjuvant capecitabine. No significant differences between the AYA and the ≥40 group in terms of clinicopathological, toxicity, pCR rate, and the rate of BCS. In univariate analysis, the LVI, nodal status, pCR, and age group were significant predictors of DFS. In multivariate analysis, only PCR and age are the only independent predictor of DFS. The median DFS was worse in the AYA population 47.8 (31.21-64.39) months vs. NR in ≥40 (p-value 0.013). In patients who achieved pCR, the estimated 5-years DFS for the AYA group was 56.1% versus 86.8% for the ≥40 group, (p-value 0.71). In patients with residual disease, PFS for AYA was 34.2 (95%CI 11.5-57) months vs. 59.5 months in the ≥40 group, (p 0.009). Conclusion: Although there is no difference in pCR between the AYA age group patient treated with NACT for TNBC and the older age group, the DFS is significantly worse in the AYA than the ≥40 age group in patients with residual disease. As well, DFS is numerically worse in the AYA age vs. the ≥40 age group in patients who achieved pCR. Citation Format: Faris Tamimi, Baha’ Sharaf, Suhaib Khater, Suhaib Al-Sawajneh, Malek Horani, Khalid M. Elrabii, Anas Zayed, Hikmat Abdel-Razeq. Neoadjuvant B27 protocol in Triple-Negative Breast Cancer: Evaluation response rate, pathological complete response rates,toxicity,and the prognosis of Adolescent and Young Adult (AYA) age group compared to older population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-06.

Comparison of diagnostic and treatment processes among pediatric and adolescents and young adults' populations suffering from acute lymphoblastic leukemia and lymphomas.

Acute lymphoblastic leukemia (ALL) and lymphomas affect both pediatric and adult populations, therefore, they might be treated by pediatric or adult centers.It has been proven that the prognosis among adolescents and young adults (AYA) is poorer than among children, which remains a subject of research. Many factors are suspected to affect the diagnostic and treatment processes in adolescents and young adults, one of them being the organization of the healthcare system.The aimof the studywas to compare the time intervals between different events on disease trajectory in pediatric and AYA groups suffering from ALL and lymphomas. We collected data on 81 patients diagnosed with ALL (50 children and 31 AYAs) and 100 patients diagnosed with lymphomas (50 children and 50 AYAs). Statistical analysis was performed in order to compare the groups. The results confirmed the hypothesis that the duration of the diagnostic process differs significantly between groups. For patients with ALL, the analyzed time intervals were significantly shorter in the pediatric group than in the AYA group: first contact with a GP - admission to Hematology Department (2 vs. 5 days; pvalue= 0.004), first contact with a GP - treatment (6 vs. 12 days, p-value=0.001), diagnosis - treatment (1 vs. 3 days, p-value=0.003). In the case of patients suffering from lymphomas, the results were similar. The analyzed time intervals were significantly shorter in the pediatric group than in the AYA group: first contact with a GP- diagnosis (21 vs. 40.5 days, p-value<0.0001), first contact with a GP - treatment (27 vs. 65 days, p-value<0.0001). Trend analysis showed that the longer patients had presented symptoms before contacting the primary care physician, the longer they waited for the beginning of treatment both in ALL and lymphomas groups (p-values=0.0129 and 0.0038 respectively). As the diagnostic and treatment processes are longer for AYA patients, actions must be undertaken in order to ensure equality and improve the healthcare system in Poland and possibly other countries.

Comparison of survival outcomes between adolescent and young adults and older adults with tongue squamous cell carcinoma: a nationwide database study using the head and neck cancer registry of Japan

This study aimed to evaluate the prognostic outcome for adolescent and young adult (AYA) generation patients with tongue squamous cell carcinoma (TSCC). Data were obtained from the Head and Neck Cancer Registry of Japan, and patients who were newly diagnosed with TSCC from 2011 to 2014 were extracted. We compared the clinical parameter and survival of the ≤ 39years old (AYA) patient group with the 40-79 (non-AYA) group. Propensity score matching (PSM) was used for survival analyses. Our cohort included 2221 patients with TSCC. AYA and non-AYA groups consisted of 258 and 1963 patients, respectively. The AYA group has a larger proportion of females than the non-AYA group (P < 0.001). Following PSM, both overall and disease-specific survival of the AYA group was significantly longer than those of the non-AYA group (P = 0.009 and P = 0.04, respectively). We demonstrated the survival superiority of AYA patients with TSCC compared to older adult patients. Therefore, our study results may reduce this anxiety by providing patients with appropriate information of prognosis for AYA patients with TSCC.

Chronic Myeloid Leukemia in Adolescents and Youngadults: Clinicopathological Variables and Outcomes

Introduction Adolescents and young adults (AYAs) are defined as those diagnosed with cancer at ages 15 through 39. [1] In Qatar we have a large number of patients that fall under the category of AYA, reflecting the fact that most of the population are relatively young working force, where the statistics confirm that the median age of the population of Qatar in 2021 is 32.5 [2]. Objective We conducted this study to find out if AYA age group differ from older age group in clinicopathological variables or outcome, which could indicate a unique disease pathology. We also compared different risk scores to find out which one is more representative of real outcome in AYA. Methodology We conducted a retrospective analysis of the files of 224 patients being treated in our center for CML. Patients' management and response assessment was done based on ELN 2013 guidelines. The analysis is done based on age at diagnosis: < 40 years (AYA) or ≥ 40 years. Results Our study included 224 patients of diverse ethnicities. Baseline characteristics for the study cohort are summarized on the attached table. Patients in the AYA group had a better prognosis based on Sokal score. Same applies for Euro/Hasfold scores. Whereas EUTOS and ELTS scores showed more comparable risk stratification between age groups (see the attached table). When comparing the outcome at 1 year, 24 patients (35.8%) from AYA group vs. 10 (14.4%) from the other group failed to achieve optimal response or had disease progression. The patients who achieved CCyR were comparable (AYA group = 21 (31.3%) vs 20 (29.0%) in the other group). With regards to MMR or deeper response the number was 22 (32.9%) in AYA group vs 39 (56.3%) in the other group. The cumulative MMR was significantly lower in AYA group compared with the older patients' group: 55 (56.7%) vs 69 (73.4%) p=0.016. However, there was no significant difference with regards to DMR: 36 (37.1%) vs 44 (46.8%) p = 0.175 (but still with higher percentage of patients achieving DMR in older age group). Discussion AYA are an important patient population which is underrepresented in the studies done in CML. Most recommendations for CML management are extracted from studies including patients who are much older with a small fraction qualifying as AYA. Some unique challenges for this population include fertility issues, access to health care, and survivorship concerns. Treatment free remissions are more important and more relevant for this age group. Our study shows that AYA patients present more aggressively with higher WBC count, lower Hb lever, and bigger spleens. Additionally, more patients in AYA group were diagnosed in blast phase. However, Sokal/Euro risk scores classified more patients in this group as lower risk; whereas EUTOS and ELTS risk scores placed the patients in comparable risk groups; despite that, outcome was worse both at 1 year and at last follow up. This may suggest that this patient population may have different underlying disease biology which may warrant different risk stratification and different approach to management. In conclusion, AYA present a unique age group, and more studies are needed to clarify the differences in disease biology and possible effect on outcome, as well as possibly formulate a new risk score for this age group.

Characteristics of Cancers in Adolescents and Young Adults Compared with Those in Adults in Their 60s: A Single-Center Experience

Introduction: Cancer is one of the main causes of death among adolescents and young adults (AYAs) aged 15–39 years. The improvement in overall 5-year survival in AYA cancer patients was far below than that of adult cancer patients. The purpose of this study was to clarify the features of cancer in AYAs by comparing them with those of controls. Methods: Patients in the cancer registry of the University of Tsukuba Hospital between 2007 and 2017 (median age, 65 years) were included in this study. We used patients between the ages of 64 and 66 years as controls. We then obtained the age at diagnosis, sex, primary site, and pathological type. Results: Among 27,281 cancer patients in the registry between 2007 and 2017, 1,947 (7.1%) patients were categorized into the AYA group, and 2,354 into the control group. Among men in the AYA group, central nervous system (CNS) tumors accounted for 22.7% of all cancers, followed by germ cell tumors, 22.5%, and hematopoietic malignancies, 12.5%. Among women in the AYA group, cervical cancer accounted for 35.9% of all cancers, followed by breast cancer, 14.6%, and CNS tumors, 11.6%. The proportion of specific cancer types relative to all cancers in the CNS, thyroid, adrenal glands, germ cells, cervix uteri, hematopoietic tissues, and sarcomas was higher in the AYA group than that in the control group. Conclusion: The present results for AYAs were in sharp contrast to those for adult cancers and may be related to different modes of pathogenesis in AYAs. The identification of high-risk groups of these tumors in the AYA generation is crucial for prevention and early detection and will be a major topic for future research. While most of adult cancers are treated independently by each medical department, AYA cancers need to be treated in collaboration with experts from several departments. It is desirable to address the issues involved in applying treatments established for adult cancers to AYA cancers on a cancer-by-cancer basis.

Association of Radioiodine for Differentiated Thyroid Cancer and Second Breast Cancer in Female Adolescent and Young Adult.

BackgroundExposure to radiation is related to breast cancer occurrence. While whether the radioiodine (RAI) increases the risk of second breast cancer (SBC) in female differentiated thyroid cancer (DTC) patients is not well addressed.MethodsAll patients were identified from Surveillance, Epidemiology, and End Results database. At least a 5-year latency was guaranteed since exposure to RAI. Fine and Gray model was used to calculate the cumulative incidence and hazards ratios (HR) and 95% confidence interval (CI). Standardized incidence ratio (SIR) was calculated by Poisson regression analysis. Propensity score matching was used for match analysis. Survival analyses were performed by the Kaplan-Meier method and the log-rank test.ResultsA total of 406 out of 16,850 patients in the RAI group and 733 out of 22,135 patients in the no RAI group developed SBC. The cumulative incidences of SBC were higher in patients with RAI compared with patients without RAI in the adolescent and young adult (AYA) group and the middle-aged adult group. In the AYA group, patients with RAI had increased HR (1.65; 95% CI, 1.33–2.05, p < 0.001) compared with those without RAI, and the HR increased slightly with latency. In addition, the SIR (1.21; 95% CI, 1.02–1.44, p < 0.05) increased compared with the general population. Whereas, in the middle-aged adult group, only a slightly higher HR (1.18) was found. The survival after SBC was inferior to those with matched only primary breast cancer.ConclusionsRAI treatment increased the risk of SBC in female AYA DTC patients. A long-term follow-up should be performed in this population.

Comparisons of Outcomes Between Adolescent and Young Adult with Older Patients After Radical Resection of Pancreatic Ductal Adenocarcinoma by Propensity Score Matching: A Single-Center Study.

PurposeAdolescent and young adult (AYA) pancreatic ductal adenocarcinoma (PDAC) occurs in patients below 40 years old. Whether AYA patients have worse outcomes compared with older patients is still controversial. The purpose of this study is to compare the outcomes of AYA patients and older patients after radical surgery for PDAC.MethodsA single-center, retrospective, cohort study was conducted in patients who underwent radical surgery for PDAC in Xiangya Hospital Central South University from January 2007 to December 2019. The clinicopathological data and results of patients with PDAC were collected and analyzed retrospectively. They were divided into AYA group and older group based on age (<40, AYA group; ≥40, older group). Based on all the considered covariates except age, we estimated 1:2 case propensity score matching (PSM).ResultsA total of 1033 cases were enrolled, 46 cases (4.45%) in the AYA group. Both before and after PSM, the AYA patients have a higher preoperative CA19-9 than the older patients (P < 0.001) and (P < 0.001). Pathological results showed that AYA group had a higher microvascular invasion rate (P < 0.001 and P = 0.045) than older group. The median time of overall survival (OS) in AYA group and older group were 13 months (95% CI = 11.50–14.50) and 14 months (95% CI = 13.50–14.50), respectively. Additionally, AYA group have a worse 2-year OS rate than older group (8.70% vs 25.23%, P = 0.011 and 8.70% vs 25.00%, P = 0.023). According to the Log rank test, AYA group have a worse cumulative OS rate than older group (P = 0.002) and (P = 0.030), respectively.ConclusionPDAC might be more aggressive in AYA, and the cumulative OS after radical PDAC surgery in AYA patients is worse than that in older patients.

Abstract P038: Early phase II clinical trial results for 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in adolescents and young adults (AYA) with brain cancers

Abstract Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N7-guanine and N4-cytosine that is currently in Phase II trial in AYA subjects with cancer that have CNS involvement. The aims for the trials are to assess clinical responses, monitor toxicities, safety and confirm the MTDs for IV administered DM-CHOC-PEN (IND 68,876) to AYA subjects with cancer involving the CNS. We report here responses and toxicities observed to date in Phases I &amp; II DM-CHOC-PEN clinical trials with AYA subjects that had cancer involving the CNS. Subjects &amp; Methods: DM-CHOC-PEN was administered as a 3-hr IV infusion once every 21 days to AYA subjects. The dosing schedule was 2-tiered: subjects with liver involvement received 85.8 mg/m2 and subjects with normal liver function received 98.7 mg/m2. Results: nineteen (19) AYA subjects with CNS involvement have been treated to date. The common tumor types treated were oligoastrocytoma, astrocytoma, GBM; leukemia (ALL), lymphoma (NHL), melanoma, breast and lung cancers (NSCL). Three (3) AYA patients are currently being followed with diagnoses of breast cancer, astrocytoma, and lung cancer and have had good qualities of life at 12, 59 and 72+ mos. All patients have been followed with lab tests, scans (RECIST 1.1) and virtual exams. The drug was well tolerated. The most common adverse effect was fatigue (17%). No neuro/cognitive, liver dysfunction, hematological, cardiac, renal or GI toxicities were observed. PK modeling revealed that AUCs were parallel for all dose levels. The Cmax for DM-CHOC-PEN and DM-PEN (4-demethylpenclomedine, a metabolite) were 3 and 24 hours, respectively for the AYA subjects; similar to what was seen for older adults. The drug and metabolite were still detectable in plasma and rbcs for 21 to 50 days in the AYA (15 – 39 y/o) group vs. 3 to &amp;lt; 21 days (previously reported for adult subjects (&amp;gt;60 y/o) (AACR #1185, 2013). Differences in PK profiles between AYA and older adult subjects will also be reviewed in depth. Conclusion: DM-CHOC-PEN is safe for usage and has produced objective responses with manageable toxicities in AYA subjects with cancer involving the CNS. Complete data on subject responses and observed toxicities will be presented. We propose a 3-stage mechanism for drug entry into the CNS and into cancer cells via reversible binding with RBCs and then association with L-glutamine transport into cells. Supported by NCI/SBIR grants – R43/44CA132257 and R43CA203351 and NIH NIGMS 1 U54 GM104940. Citation Format: Lee Roy Morgan, Roy S. Weiner, Tallat Mahmood, Marcus L. Ware, Andrew H. Rodgers, Manish Bhandari, Philip Friendlander. Early phase II clinical trial results for 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in adolescents and young adults (AYA) with brain cancers [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P038.

Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukemia: Why Do Adolescents and Young Adults Outcomes Differ from Those of Children? a Study on Behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)

Introduction:Adolescents and Young Adults (AYA) represent a specific population in the Acute Lymphoblastic Leukemia (ALL) landscape, often presenting high-risk diseases and increased chemotherapy-related toxicities. Indications of Hematopoietic Stem Cell Transplantation for pediatric patients (HSCT) have been restricted to those with early poor response to chemotherapy. The same trend has led to a decrease of HSCT indications in AYAs, which are nevertheless still more frequent than in younger counterpart. Outcomes of AYAs after HSCT seemed to be worse than the ones of children in two previous studies published in 2013 and 2014. In Minneapolis, the decrease of overall survival in AYA was attributed to an excess of Treatment Related mortality (TRM) (28% versus 14%; p=0.04), but because of small numbers, factors influencing TRM were not identified. Our study aimed to compare, in a large cohort, the outcomes of children and AYA with ALL after HSCT and to determine factors influencing potential differences.Material and Methods:All patients aged between 1 and 25 years, reported in the SFGM-TC (Francophone Society of bone marrow transplantation and cellular therapy) registry, who received a first HSCT in treatment for ALL between 2005 and 2012 were included. The AYA group was defined by age range between 15 and 25 years old, according to European studies and the SFGM-TC. Data about diagnosis and transplantation procedure were prospectively collected in the registry. Before transplant procedure, patients or their parents/guardians provide a signed consent in order to be included in the registry.Results:891 patients were included, 494 children and 397 AYA. Median time of follow up was 45.6 months (0 to 114). HSCT was performed in first CR for 56.8% of the AYAs, whereas 57.5% of children received HSCT in second CR or more advanced phase (p<0.001). HSCT procedures mainly included a Myelo-Ablative Conditioning (MAC) regimen. TBI was used more frequently in AYAs than in children (90.1% versus 83.1%, p=0.003). Bone Marrow (BM) or Cord-Blood (CB) were often used in children 60.2% and 29.4% versus 55.6% and 16.4% in AYA group respectively (p < 0.0001) . Peripheral Blood Stem Cells (PBSC) were more frequently used for AYA (28%) than for children 10.3% (p < 0.0001). Moreover, when being transplanted in an adult center, PBSC were more commonly used for AYA (30% of AYA's HSCT in adult centers versus 21.2% of AYA's HSCT in pediatric centers, p=0.051). BM and PBSC cells were provided by a match sibling donor (MSD) in 40.2% of children and 43.4% of AYAs and from a MUD in 57.2% and 55.1% of cases respectively (p = 0.474). Anti-thymoglobulins (ATG) were used for 336 patients (48% of children and 26% of AYA patients, p<0.001). See patient's characteristics in Table.Five-year OS was lower in AYA 53.1% versus 64% (p = 0.0012) and we confirmed higher 5-years TRM in AYA 19% versus 13% (p=0.04). TRM incidence markedly rose after 10 years of age (from 9% before 10 years old to 20% between 10 and 15 years, and 17% after 15 years).Graft versus host disease and Relapse Free Survival probability (GRFS) was lower in AYA: 36% versus 47% (p=0.007), while Cumulative Incidence of Relapse (CIR) and acute Graft versus Host Disease (GvHD) incidence were both similar in our two groups: 32% and 61% in AYAs versus 27% and 59% in children, (p=0.19 and p=0.62), respectively. Thus, chronic GvHD, which occurred more frequently in AYA than in children (32% versus 19%, p<0.001), mainly impact post-HSCT morbi-mortality in AYA (Figure 1 and 2).In our multivariate analysis, two factors were associated with higher risk of cGvHD: use of PBSC as stem cell source (HR 1.41 [0.96-2.07], p=0.083), and absence of ATG use (HR associated with use of ATG: 0.62 [0.42-0.92], p=0.017) (Figure 3). Of note a subgroup analysis in patients who received a bone marrow transplant after a MAC, showed no TRM difference between AYA and children.Conclusion:AYA or patients aged more than 10 years, compared to ones aged less than 10 years have a worse outcome after HSCT for ALL. Excess of death in this specific population is mainly due cGvHD. Transplantation practices in those patients, particularly choice of stem cells source and GvHD prophylaxis, should be discussed. Their treatment adherence should also be questioned and reinforced by development of multidisciplinary teams. [Display omitted] DisclosuresPeffault De Latour: Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Amgen: Consultancy, Other, Research Funding; Jazz Pharmaceuticals: Honoraria; Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Forcade: Novartis: Other: travel grant.