Myeloid Leukemia In Adolescents Research Articles

Chronic Myeloid Leukemia in Adolescents and Young Adults: Clinicopathological Variables and Outcomes.

Adolescents and young adults (AYAs) diagnosed with chronic myeloid leukemia (CML) constitute a significant demographic group, particularly in regions with youthful populations like Qatar. Despite the global median age of CML diagnosis being 65 years, Qatar's age distribution reflects a younger cohort. This study investigates whether AYAs with CML exhibit distinct clinicopathological characteristics or outcomes compared to older age groups. A total of 224 CML patients were enrolled, including 114 AYAs (defined as ages 15 through 39). Demographic and clinical parameters, including gender, BMI, BCR-ABL1 transcript type, white blood cell (WBC) count, hemoglobin level, platelet count, and spleen size, were compared between AYAs and older patients. Prognostic scoring systems (Sokal, Hasford, EUTOS, and ELTS) and molecular response rates (MMR and DMR) were also evaluated. AYAs demonstrated higher WBC counts at diagnosis (median 142.3 vs. 120; p = 0.037) and lower hemoglobin levels (10.5 vs. 11.40; p = 0.004) compared to older patients. Spleen size was significantly larger in AYAs (18.8 vs. 15.5; p = 0.001). While AYAs showed better prognostic scores by Sokal and Hasford criteria, EUTOS and ELTS scores indicated comparable risk stratification. However, AYAs exhibited lower rates of MMR (56.7 vs. 73.4%; p = 0.016) and achieved MMR at a slower pace (median time 130 vs. 103 months; p = 0.064). Similarly, the percentage of DMR was lower in AYAs (37.1 vs. 46.8%; p = 0.175). Despite their younger age, AYAs with CML displayed poorer prognoses compared to older patients. These findings underscore the importance of tailored management strategies for AYAs with CML to optimize outcomes in this distinct patient population. AYAs are underrepresented in CML studies and risk scores, so this is the focus of this study.

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

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

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.

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.

Chronic Myeloid Leukemia in Adolescents and Young Adults: A Single Institute Experience

Background and Objectives: CML is a myeloproliferative neoplasm characterized by the dysregulated production and uncontrolled proliferation of mature and maturing granulocytes with fairly normal differentiation. It mainly affects adults, and is rarely seen in children. The average age at diagnosis of CML is around 64 years. There are few studies describing CML in adolescents and young adults. In Qatar we have one of the largest cohorts of adolescents and young adults with CML. This study aims to study this cohort and find out if there are any differences from older patients with CML. Methods: A retrospective analysis of 169 patients with CML treated at NCCCR over a 23-year period, 83 of them are younger than 40 years at diagnosis (adolescents and young adults) vs. 86 age 40 or older at diagnosis (controls). Comparison was done of all characteristics at diagnosis, including: gender, BMI, ethnicity, CBC parameters, spleen size, Sokal score, bone marrow findings, treatment modality, with response assessment using ELN guidelines. Results: Both groups were matched with regards to gender and ethnicity. Adolescents and young adults had higher WBC count and larger spleen on diagnosis compared to controls (174.1 vs. 142.2; and 18.0 vs. 15.6). 4 young patients presented in blast-phase vs. 1 in control group. 5 adolescents and young adults underwent allogeneic stem cell transplant vs. 1 patient in the control group. During a mean follow up of 70.7 months in adolescents and young adults vs. 72.7 months in the control group there were 2 deaths vs. 1 respectively. However, there were no other significant differences between the two groups, with regards to TKI used, or response at 1 year / latest assessment. Conclusions: Based on this data we may conclude that CML present more aggressively in adolescents and young adults as compared with older patients, however there is no difference in outcome. This might reflect different underlying etiology / better tolerance to treatment in the younger group. Table Disclosures No relevant conflicts of interest to declare.

Chronic Myeloid Leukemia in Adolescents and Young Adults Treated with Generic Form of Imatinib in Resource Limited Setting: A Single Center Experience from Myanmar

Chronic myeloid leukemia (CML) is an acquired myelo-proliferative disorder characterized by the presence of BCR-ABL1 fusion transcript with deregulated tyrosine kinase activity. Leukemias are one of the leading causes of cancer related deaths in adolescents and young adults (AYA) particularly in resource limited countries. Recent democratic government in Myanmar holds supportive policies for treatment of cancers in younger population and subsidizes some therapies including imatinib mesylate, a selective BCR-ABL 1 tyrosine kinase inhibitor, although there is still limitation for cytogenetic and molecular monitoring of therapy. This study on response to imatinib in newly diagnosed chronic phase CML was carried out during January 2016 to February 2018 at the North Okkalapa General and Teaching Hospital of Yangon, Myanmar where molecularly confirmed new CML in chronic phase were treated with generic form of imatinib bought by hospital tender system, Unitinib (United Biotech (P) ltd. India) followed by cytogenetic analysis of bone marrow and molecular detection of BCR-ABL1 transcript from peripheral blood by in house real time PCR machine at one year. They are divided into AYA (aged 15-39 years) and adult age groups (40 years and older) and clinical parameters and response to treatment with imatinib 400mg per day were compared. Among 56 cases (median age of 39.5 years, male to female ratio of 1.5:1), half were AYA (28 of 56) with median age of 28.5 years compared to 50 years in adult group with higher male to female ratio of 3.6:1 in AYA group. Patients in AYA had larger spleen size (11 vs 5.5 cm) and higher median white cell count compared to adults (366 x 109/l vs 224 x 109/l) although initial platelet count, peripheral blood eosinophil, basophil and blast percent and Sokal score were comparable. Additional chromosomal abnormalities were detected in 2 AYA and 3 adults with CML. There was no difference in complete haematologic response at 3 and 12 months between AYA and adults (96.4% vs 96.4% and 92.9% vs 89.3% respectively). At 12 months, complete cytogenetic response of AYA at 67.9% was less than 75.0% of adults, it was statistically not significant. Using in house molecular method although not standardized, 14.3% of AYA and 32.1% of adults were molecularly undetectable at one year. The response of AYA to imatinib in this study was comparable to adults despite having adverse prognostic features and receiving only generic forms of treatment in resource limited setting and it would further help support from authorities for leukemia in younger population. DisclosuresNo relevant conflicts of interest to declare.

Acute myeloid leukemia in adolescents and young adults: from the viewpoint of pediatricians.

It is well known that adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) should be treated based on pediatric ALL protocol, which could yield better survival rates. However, an optimal treatment strategy for AYAs with acute myeloid leukemia (AML) is not yet established and corresponding data are limited. Compared with ALL, clinical and biological characteristics of pediatric and adult AML are relatively similar. Moreover, treatment strategy is quite similar, although pediatric protocols are more intensive and transplant indications are narrower. Previous reports show that AYAs with AML have similar to relatively lower survival rates and higher treatment-related mortality than children with AML. These results indicated that intensive pediatric chemotherapy is effective for preventing AML relapse in AYAs but higher toxicity rates compensates overall survival. To improve the outcomes of AYAs with AML, it is essential to develop optimal intensive chemotherapy, introduce novel targeted therapies, and adopt better risk stratification, particularly to determine appropriate transplant indications. These strategies should be accomplished by close cooperation between pediatric hematologists/oncologists and adult hematologists.

Acute myeloid leukemia in adolescents and young adults: from the viewpoint of physicians.

Based on various studies, the survival of adolescent and young adults (AYAs) with acute myeloid leukemia (AML) was reportedly similar to or worse than younger children. AYAs with AML treated in adult institutions are usually offered the same treatment as that of the older adults. Although pediatric protocols generally include intensified regimens compared with adult protocols, it is still controversial whether an intensified pediatric AML regimen results in an improved survival for the AYA population. Somatic mutations have proven to be significantly prognostic in AML. Although such molecular markers are becoming increasingly important as a means of risk stratification for both children and adults with AML, the prevalence and significance of somatic mutations remain largely unknown in AYAs with AML. In addition to the biological characteristics of cancer, non-biological factors, such as compliance with treatment, may influence the treatment outcomes of AYAs. AYAs have specific and unique needs that are different from children and older adults such as psychosocial care, transition from the pediatric to adult care environment, and fertility considerations among long-term survivors. A further multidisciplinary approach for AYAs with AML is still an issue among adult institutes.

Defining the Genomic Make up of Acute Myeloid Leukemia in Adolescents and Young Adults (AYA): Report from COG AAML03P1, AAML531 and SWOG S0106

Acute myeloid leukemia (AML) is a genetically heterogeneous and highly resistant hematopoietic malignancy. Despite survival gains over the past several decades, adolescent and young adult (AYA) with AML demonstrate a consistent survival disadvantage as compared to younger patients (age < 15 years). This discrepancy in outcome is likely due to distinct aspects of disease biology in this patient population.In recent years several somatic mutations with biological, prognostic and therapeutic significance have been identified in patients with AML. Nonetheless, these studies have been conducted in pediatric and older adult patients only. Therefore, the prevalence of these somatic mutations remains largely unknown in AYA patients.Herein, we investigate the prevalence of common AML-associated mutations in AYA, here defined as age 15 to 39 years, aiming to characterize the disease and identify mutations that are relevant for therapeutic strategy in this age group. We compare the distribution of these mutations in the 3 age groups: children (age< 15 years), AYA (age 15 to 39 years) and older adults (age> 39 years).Patients enrolled in the COG trials AAML03P1 and AAML0531 and in the SWOG trial S0106 were eligible for this study. Acute promyelocytic leukemia patients were excluded. AAML03P1 enrolled patients 0 to 21 years, AAML0531 enrolled patients 0 to 30 years and S0106 enrolled patients 18 to 60 years of age. We analyzed 1722 patients (age range 0 to 60 years) with newly diagnosed AML. Pre-treatment samples were obtained from AAML03P1 and AAML531 (N=1361) and S0106 (N=361). Mutation analyses were performed by a combination of targeted capture and fragment length analysis. Chi-square test was used to compare variables.The prevalence of each mutation according to age groups is shown on Table 1. Similarly to what is observed in children and older adults, NPM1 and FLT3- ITD are the two most common mutations in AYA patients with a prevalence of 19% and 14%, respectively. When compared to the other age groups, we observe a significant increase in prevalence of both FLT3- ITD and NPM1 with aging, with a significant higher prevalence of these mutations in older adults as compared to AYA and children.Previous studies have shown that mutations in epigenetic modifier genes are enriched in adults with AML as compared to pediatric patients. We evaluated the prevalence of mutations in these genes in the 3 age groups. We observed a significant increase in prevalence in mutations in all epigenetic modifiers genes with aging (Table 1). The combined prevalence of mutation in these genes (IDH1, IDH2, DNMT3A, ASXL1 and IDH1/2) in children, AYA and older adults were 9%, 19% and 39% (P< 0.0001), respectively, highlighting the clinical and biological importance of this class of genes in older patients.In this large collaborative study, we define for the first time the prevalence of common mutations in AYA with AML. Our study shows that the genomic make up of patients with AYA are different from children and older adults, suggesting unique biology of the disease in this age group. Our data raise questions about future therapeutic strategies, which should take into account the age distribution of these genetic lesions. Finally, clinical correlations to determine the prognostic significance of these mutations in AYA are underway and should provide a framework for future disease risk stratification in this age group. In summary, our data shows the distinct genomic profiling of common mutations in AYA, arguing for age specific disease risk stratification as well as therapeutic strategies in this age group.Table 1Prevalence of common mutations in children, adolescents and young adults (AYA) and older adults with AMLChildren (<15 years)AYA (15-39 years)Older adults (>40 years)P valueFLT3-ITD13%19%23%0.0006NPM16%14%32%< 0.00001CEBPA5%8%3%0.02WT16%9%5%0.154IDH1/23%7%17%< 0.00001DNMT3A0%2%16%< 0.00001ASXL12%4%7%0.007TET24%7%11%0.002 DisclosuresRadich:Novartis: Consultancy, Research Funding; Incyte: Consultancy; Gilliad: Consultancy; Ariad: Consultancy. Erba:GlycoMimetics; Janssen: Other: Data Safety & Monitoring Committees; Sunesis; Pfizer; Daiichi Sankyo; Ariad: Consultancy; Millennium/Takeda; Celator; Astellas: Research Funding; Seattle Genetics; Amgen: Consultancy, Research Funding; Novartis; Incyte; Celgene: Consultancy, Patents & Royalties.

Acute Myeloid Leukemia in Adolescents and Young Adults Treated in Pediatric and Adult Departments in the Nordic Countries.

Studies on adolescents and young adults with acute lymphoblastic leukemia suggest better results when using pediatric protocols for adult patients, while corresponding data for acute myeloid leukemia (AML) are limited. We investigated disease characteristics and outcome for de novo AML patients 10-30 years old treated in pediatric or adult departments. We included 166 patients 10-18 years of age with AML treated according to the pediatric NOPHO-protocols (1993-2009) compared with 253 patients aged 15-30 years treated in hematology departments (1996-2009) in the Nordic countries. The incidence of AML was 4.9/million/year for the age group 10-14 years, 6.5 for 15-18 years, and 6.9 for 19-30 years. Acute promyelocytic leukemia (APL) was more frequent in adults and in females of all ages. Pediatric patients with APL had similar overall survival as pediatric patients without APL. Overall survival at 5 years was 60% (52-68%) for pediatric patients compared to 65% (58-70%) for adult patients. Cytogenetics and presenting white blood cell count were the only independent prognostic factors for overall survival. Age was not an independent prognostic factor. No difference was found in outcome for AML patients age 10-30 years treated according to pediatric as compared to adult protocols.

Acute Myeloid Leukemia in Adolescents and Young Adults (AYA): The MD Anderson Cancer Center (MDACC) Experience

Background: Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic neoplasms demonstrating clonal proliferation of myeloid precursors and is typically a disease of older adults. In acute lymphoblastic leukemia (ALL) adolescent and young adult (AYA) patients (pts) have a distinct outcome, possibly influenced by type of therapy (i.e., usually better with more intensive regimens). There is little information about outcome of AML in AYA.Aims: To define the characteristics and outcome of AYA pts with AML treated at MDACC.Methods: We retrospectively analyzed the data of all pts with AML treated at MDACC from 1965 to 2008. Those aged 16 to 21 years were defined as AYA.Results: Among 3934 adult pts seen during this period, 163 (4%) were AYA. The median age was 19 yrs. These included 27 (17%) pts with Core Binding Factor (CBF)-AML [inv(16), t (8:21)]and 19 pts (12%) with acute promyelocytic leukemia (APL). Among other evaluable pts, 50% had diploid cytogenetics, 39% miscellaneous changes, and 11% 5-and/or 7- abnormalities. Antecedent hematologic disorders were present in 33 (20%) and AML was a secondary malignancy in 6%. Among 20 evaluable pts, FLT3 ITD was documented in 4 and mutation in 2. CR rates were 89% for CBF AML, 79% for APL, and 75% for all others. The median survival for the total group was 88 weeks (wks) with 36% alive at 3 yrs, and median CR duration of 67 wks (30% CR at 3 yrs). Outcome is better for pts with CBF leukemias (3-yr survival 56%, CR duration 49%) and APL (3-yr survival 51%, CR duration 36%) compared to other AML (3-yr survival 28%, CR duration 24%). CR rates have improved from 71% in 1965–84, to 85% in 1985–94 and 83% after 1994. Similarly, overall survival (OS) has increased during the same time periods (3-yr survival 18%, 44%, and 53%, respectively) together with CR duration (3-yr CR duration 21%, 32% and 39%, respectively) as early mortality has decreased (11%, 8%, and 4%, respectively). To compare outcome with older adults, we focused on those with diploid cytogenetics (Table 1):Percentage by age groupOutcome16–2122–4546–60>60CR81756854Induction mortality21113243-year survival463628163-year remission duration39323022Conclusion: The outcome of AYA pts with AML is significantly better than that of older adults with AML. Despite these improvements over time, there is still significant room for improvement in this area, particularly among those with AML other than CBF and APL. Exploration of new treatment options is needed in this patient population.