Correlation between epigenetic modifier gene mutations and prognosis of patients with acute lymphoblastic leukemia: a systematic review and meta-analysis

Low Expression Of BCL11B Predicts Poor Overall Survival In Adult Standard Risk T-ALL

Effect of MRD Level after Induction Therapy and Post-Remission Treatment on Prognosis of ALL Patients

GATA3 rs3824662A allele in B-cell acute lymphoblastic leukemia in adults, adolescents and young adults: association with CRLF2 rearrangement and poor prognosis.

Impact of Thromboembolism on Overall and Event-Free Survival in Children with Acute Lymphoblastic

High prevalence and inferior long-term outcomes for TP53 mutations in therapy-related acute lymphoblastic leukemia.

Introduction: Among young patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), minority race/ethnicity and lack of health insurance have been associated with lower survival. We sought to evaluate the impact of neighborhood socioeconomic status (nSES) and neighborhood archetype on early mortality and overall survival among patients with ALL and AML in California. We hypothesized that living in low SES neighborhoods will be associated with lower survival among young patients with acute leukemia. Methods: Patients aged 0-39 years reported to the California Cancer Registry with a diagnosis of ALL or AML between 2006 and 2016 were included. Using a previously developed composite measure, nSES quintiles were evaluated as the primary exposure of interest. Latent class analysis was used to generate neighborhood archetypes based on 39 social and built environment attributes at the block group level, which were evaluated as an exploratory exposure. Patients were observed from diagnosis through last available follow up. Cox proportional hazards univariate models were used to estimate crude hazard ratios (HR) for early death (within 60 days following diagnosis) and overall survival (OS). Results: Of the 8761 patients included, 6338 were diagnosed with ALL and 2423 were diagnosed with AML. Median follow up time was 3.2 and 2.1 years, respectively. Minority race/ethnicity, older age (>19 years), lack of insurance, lack of chemotherapy, and treatment at an adult center were associated with lower OS in univariate models. Patients in the lowest quintile of nSES had an increased risk of early mortality for both ALL (HR 1.91, 95% CI 1.06, 3.47) and AML (HR 2.01, 95% CI 1.17, 3.45) relative to the highest quintile of nSES. Likewise, patients in the lowest quintile of nSES had lower OS for both ALL (HR 2.10, 95% CI 1.68, 2.62) and AML (HR 1.40, 95% CI 1.12, 1.76). A dose effect was observed with worse OS observed among quintiles 2-4 as well. In patients with ALL, relative to the highest status neighborhood archetype, all other neighborhood archetypes demonstrated lower OS, with the most pronounced effects in inner city (HR 2.35, 95% CI 1.79, 3.09), Hispanic small towns (HR 2.33, 95% CI 1.74, 3.11), and mixed SES class suburban neighborhoods (HR 2.27, 95% CI 1.65, 3.12). While there was a suggestion of differences by archetype among AML patients, none reached statistical significance. Conclusions: The substantial crude effect of neighborhood SES on early mortality and overall survival highlights an important disparity. Multivariable adjustment for other known predictors of survival is underway. When other aspects of the social/built environment are incorporated, the magnitude of the effect grows, suggesting that nSES interacts with other neighborhood factors such as the racial/ethnic makeup. The greater effects of neighborhood among ALL patients relative to AML patients may be linked to the prolonged, outpatient nature of the therapy and difficulties with treatment adherence among vulnerable populations. Citation Format: Lena E Winestone, Juan Yang, Daphne Y Lichtensztajn, Renata Abrahao, Theresa H Keegan, Iona Cheng, Scarlett L Gomez, Salma Shariff-Marco. Impact of neighborhood socioeconomic status on survival among young patients with acute leukemia in California [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C067.

Trends of Obesity over Time and Its Prognostic Significance in Children and Adolescents with Newly-Diagnosed Acute Lymphoblastic Leukemia in Canada: A Population-Based Study

Improved Post-Transplant Outcomes over Time for Older Patients with Acute Lymphoblastic Leukemia in First Complete Remission. a Study from the EBMT Acute Leukemia Working Party

Molecular Characterization of Adult Acute Lymphoblastic Leukemia Identifies a Subgroup with Myeloid Mutations and Pre-Existing Clonal Hematopoiesis

Differential prognostic impact of chromatin modifier mutations in peripheral T-cell lymphoma: KMT2A emerges as a critical biomarker

Impact of TP53 Mutation on Survival Outcomes in Acute Lymphoblastic Leukemia at a Tertiary Center

DNA methyl-transferase 3A (DNMT3A) mutation has recently been identified as an independent risk factor for patients with acute myeloid leukemia (AML). However, reports are scanty on its rate and subsequent impact on patients with acute lymphoblastic leukemia (ALL), especially in Chinese population. In this study, we investigated the incidence and prognostic implication of DNMT3A mutation in 57 Chinese adult ALL patients. A total of 3 (5.3%) T-ALL cases were found to have the DNMT3A R882H mutation, which was significantly greater than that found in B-ALL subtype (P=0.048). The patients aged between 40 and 60 years old had higher mutation rate than other age groups (P=0.042). Patients with DNMT3A mutation had shorter overall survival (OS) than their wild-type counterparts. Our study demonstrated that Chinese ALL patients might develop DNMT3A mutation, which exerts a negative impact on their prognosis. These findings might help in risk stratification and treatment choice for Chinese ALL patients.

Prognostic Impact of Different High Risk Features in Allogeneic Stem Cell Transplantation for Acute Lymphoblastic Leukemia in First Complete Remission.

The association between cytokine receptor-like factor 2 (CRLF2) and clinical outcomes in acute lymphoblastic leukemia (ALL) has been a topic of ongoing debate, with divergent findings. This article intended to investigate the influence of CRLF2 alterations on ALL prognosis. Following the PRISMA 2020 guidelines, this meta-analysis was conducted. Hazard ratio (HR) values and confidence intervals (CIs) were the primary statistical measures used. Data heterogeneity was judged using the chi-square test and I2 statistic. Publication bias was appraised with funnel plots, Begg's test, and Egger's test. 16 studies with 6771 patients were finally screened out. CRLF2 over-expression (CRLF2 OE) was associated with poorer event-free survival (EFS) (HR = 1.70, 95% CI = 1.18-2.44, P = 0.004) and relapse-free survival (RFS) (HR = 1.70, 95% CI = 1.28-2.24, P = 0.000) in pediatric ALL. Patients with CRLF2-deregulation (CRLF2-d), also known as CRLF2 rearrangement, exhibited shorter overall survival (OS) (HR = 2.22, 95% CI = 1.49-3.32, P = 0.000), EFS (HR = 1.93, 95% CI = 1.43-2.60, P = 0.000), and RFS (HR = 2.2, 95% CI = 1.53-3.18, P = 0.000) compared to those without CRLF2-d. Subgroup analysis of multivariate HRs and corresponding CIs indicated that childhood with CRLF2 OE had a shorter RFS (HR = 1.70, 95% CI = 1.28-2.24, P = 0.006), and CRLF2-d was identified as an independent prognostic biomarker for OS (HR = 2.22, 95% CI = 1.49-3.32, P = 0.000), EFS (HR = 1.95, 95% CI = 1.44-2.64, P = 0.000), and RFS (HR = 2.2, 95% CI = 1.53-3.18, P = 0.000) in pediatric ALL patients. Both CRLF2 OE and CRLF2-d are associated with poor prognosis in ALL patients.

Impact of polymorphisms in apoptosis-related genes on the outcome of childhood acute lymphoblastic leukaemia.