Background: Acute erythroid leukemia (AEL), also known as pure erythroid leukemia, is a rare subtype of acute myeloid leukemia (AML) characterized by the proliferation of malignant erythroid precursors. Outcome data at the population level are scarce. Methods: We performed a retrospective analysis of the Surveillance Epidemiology and End Results (SEER) database. All cases with a histologically confirmed diagnosis of acute (pure) erythroid leukemia during the period of 2000–2019 were included in the study. The Kaplan–Meier method was used to perform survival analysis. The significance of differences between overall survival (OS) was analyzed using the log-rank test. Results: In total, 968 patients were included in the study. The median age was 68 years (range 0–95), 62% of patients were males, and 62.5% (n = 605) were treated with chemotherapy. The median OS for <18, 18–49, 50–64, 65–79 and 80+ age groups was 69, 18, 8, 3 and 1 month, respectively (p < 0.0001). Patients who received chemotherapy had significantly improved OS compared to patients who did not, among both adults (p < 0.0001) and children (p = 0.004). There were no significant differences in OS based on sex, race, ethnicity and median household income. Median OS for adults diagnosed in 2000–2004, 2005–2009, 2010–2014, 2015–2019 was 4, 6, 6 and 3 months, respectively, with no significant differences in OS between these groups. Conclusion: AEL occurs in all age groups but is most common in the elderly. Outcomes are poor with current chemotherapeutic agents, with no improvement in the last two decades. This study stresses the urgent need for investigational agents.
OBJECTIVE
Tumor-associated microglia and macrophages (TAMs) influence brain tumor biology and promote tumor-proliferating phenotype. Studies have shown these cell types predict outcomes in various tumor sites with limited evidence in high-grade gliomas (HGG). In this study, we assessed the presence of immune cell infiltrate (ICI) and overall survival (OS) in HGGs.
METHODS
A total of 97 consecutively treated patients with primary HGG with complete gene expression profiling were identified from our IRB-approved institutional tissue biorepository. Patients underwent primary surgical resection between 02/2004 and 03/2011. Gene expression levels were assessed by Affymetrix Hu-RSTA assays (Affymetrix; Santa Clara, CA). CIBERSORT estimated the presence of ICI via gene expression deconvolution. Tumor characteristics and the presence of 22 individual ICI subtypes were assessed with respect to OS. Time-to-event analyses were performed with Kaplan-Meier estimates and compared via log-rank test. Associations between the ICI and outcomes were explored using Cox-regression. P< 0.05 (two-tailed) was considered statistically significant.
RESULTS
Median follow-up from primary surgical resection was 12.8 months (range: 0.1-162.8), and median age was 58 years (20-85). Most patients were male (n=63; 65%) and had grade 4 tumors (n=71; 73%). OS differed by grade with 24-month actuarial OS rates of 81% and 34% (P< 0.0001) for grade 3 and 4 gliomas, respectively. The presence of M0 (HR 2.2; 95% CI 1.4-3.6; P=0.001), M1 (HR 1.8; 95%CI 1.1-2.9; P=0.01), and M2 macrophages (HR 1.9; 95%CI 1.2-3.2; P=0.007) predicted OS. No other ICI subtypes were predictive of OS. The presence of M0- and M2-polarized macrophages were more common in grade 4 compared to grade 3 gliomas 46% vs. 11% (P=0.002) and 69% vs. 31% (P=0.0007), respectively.
CONCLUSION
The increased presence of non-polarized or M2 TAMs within the glioma microenvironment was significantly associated with OS in HGG. Their presence may serve as unique stratification and a potential therapeutic target.
respectively, P = 0.0009). Studies comparing combined RT, anti-OX40, CpG, and anti-PD-1 to contemporaneous controls are ongoing. Conclusion: In a high mutational load primary mouse model of soft tissue sarcoma that is resistant to RT and anti-PD-1, RT combined with anti-OX40, CpG, and anti-PD-1 immunotherapy significantly delays tumor growth compared to historical controls. Results using this novel treatment combination with contemporaneous control groups are pending to determine if this regimen warrants further evaluation in a phase I clinical trial.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.