MECOM gene overexpression in pediatric patients with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is characterized by blocked or aberrant differentiation of hematopoietic stem cells. The MECOM gene overexpression in hematopoietic progenitors induces myeloid differentiation block, resulting in increased self-renewal and survival of these transformed progenitors. However, its exact role in AML remains unclear. We aimed to estimate the prevalence of MECOM overexpression among pediatric AML patients, and assess its impact on clinical outcome. PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction and Livak method (2ΔΔCt) were used to determine relative MECOM expression level among 243 pediatric patients with AML. MECOM overexpression was considered if the cumulative relative expression was above 1 (2-ΔΔCt) and was designated as MECOMpos. RESULTS: Of 243 AML patients tested 57(23.5%) demonstrated MECOMpos. Patients with MECOMpos had significantly lower median age. The frequency of MECOMpos was significantly higher among AML patients with 11q23 abnormalities, complex karyotypes and among high- and intermediate-risk groups compared to low-risk group (p = .014). MECOMpos patients had significantly lower overall survival (OS) (38.7 vs. 78.9%, p < .001), event-free survival (EFS) (37.3% vs. 68.4%, p < .001), and had higher cumulative incidence of relapse (49.5% vs. 23.5%, p = .002) at 36 months compared to MECOMneg patients. Multivariate analysis revealed that MECOMpos was an adverse prognostic factor for OS (hazards ratio (HR) = 2.11, 95% confidence interval (CI) 1.24-3.60, p = .006) and EFS (HR= 1.71, 95% CI 1.07-2.75, p = .025). The logistic regression model showed that MECOMpos was an independent prognostic factor regardless of minimal residual disease status post first induction therapy in the intermediate-risk group (odds ratio 2.89; 95% CI 1.19-6.57, p = .018). CONCLUSION: The aberrant MECOM gene expression is an adverse prognostic factor, especially in patients without previously known cytogenetic risk factors. Our results suggest the potential benefit from pretreatment screening for MECOM gene overexpression in newly diagnosed AML patients for better risk stratification and treatment adjustment.

Optimizing vancomycin therapeutic drug monitoring compliance in pediatric oncology: towards personalized medication management.

Aim: Vancomycin, a crucial treatment for Gram-positive bacteria, necessitates therapeutic drug monitoring (TDM) to prevent treatment failures. We investigated the healthcare professional's compliance toward TDM of vancomycin recommendations and follow-up levels. Materials & methods: We collected data from 485 patients who received vancomycin in the Children's Cancer Hospital Egypt 57357 medical records system (Cerner) over 4 months, from January to April 2020. Results: Our data shows that only 54% of patients had TDM requests from healthcare professionals for the total patients who received vancomycin treatment. The healthcare professionals' compliance with the recommendations was 91.7%, while the follow-up levels were 66.7%. Conclusion: While overall adherence to recommendations is strong, enhancing compliance with follow-up levels remains a priority for improvement.

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Integration of measurable residual disease by WT1 gene expression and flow cytometry identifies pediatric patients with high risk of relapse in acute myeloid leukemia.

Background: Molecular testing plays a pivotal role in monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML), aiding in the refinement of risk stratification and treatment guidance. Wilms tumor gene 1 (WT1) is frequently upregulated in pediatric AML and serves as a potential molecular marker for MRD. This study aimed to evaluate WT1 predictive value as an MRD marker and its impact on disease prognosis. Methods: Quantification of WT1 expression levels was analyzed using the standardized European Leukemia Network real-time quantitative polymerase chain reaction assay (qRT-PCR) among a cohort of 146 pediatric AML patients. Post-induction I and intensification I, MRD response by WT1 was assessed. Patients achieving a ≥2 log reduction in WT1MRD were categorized as good responders, while those failing to reach this threshold were classified as poor responders. Results: At diagnosis, WT1 overexpression was observed in 112 out of 146 (76.7%) patients. Significantly high levels were found in patients with M4- FAB subtype (p=0.018) and core binding fusion transcript (CBF) (RUNX1::RUNX1T1, p=0.018, CBFB::MYH11, p=0.016). Following induction treatment, good responders exhibited a reduced risk of relapse (2-year cumulative incidence of relapse [CIR] 7.9% vs 33.2%, p=0.008). Conversely, poor responders' post-intensification I showed significantly lower overall survival (OS) (51% vs 93.2%, p<0.001), event-free survival (EFS) (33.3% vs 82.6%, p<0.001), and higher CIR (66.6% vs 10.6%, p<0.001) at 24 months compared to good responders. Even after adjusting for potential confounders, it remained an independent adverse prognostic factor for OS (p=0.04) and EFS (p=0.008). High concordance rates between WT1-based MRD response and molecular MRD were observed in CBF patients. Furthermore, failure to achieve either a 3-log reduction by RT-PCR or a 2-log reduction by WT1 indicated a high risk of relapse. Combining MFC-based and WT1-based MRD results among the intermediate-risk group identified patients with unfavorable prognosis (positive predictive value [PPV] 100%, negative predictive value [NPV] 85%, and accuracy 87.5%). Conclusion: WT1MRD response post-intensification I serves as an independent prognostic factor for survival in pediatric AML. Integration of WT1 and MFC-based MRD results enhances the reliability of MRD-based prognostic stratification, particularly in patients lacking specific leukemic markers, thereby influencing treatment strategies.

A Comparison between Three Different Automated Total 25-hydroxyvitamin D Immunoassay Methods and Ultra Performance Liquid Chromatography.

OBJECTIVE: Vitamin D is a fat soluble vitamin responsible for calcium metabolism and more recently discovered effects. This led to an increase in requests for vitamin D test by clinicians. New automated assays have been introduced for 25-hydroxyvitamin D measurement. METHODS: Results from these new method have to be related to a Standard method to obtain best results for practical usage. In our study, one hundred venous blood samples were analyzed for 25-OH vitamin D on three immunological methods in our lab and correlated with ultra-performance liquid chromatography (UPLC) method as a reference method. RESULTS: Statistically analysis of results obtained for correlations between the 3 methods against the reference UPLC was done by Spearman's Correlation. It showed positive correlation in all methods with significant p value < 0.001. Differences and biases between methods were evaluated using a Bland-Altman plot and Cohen's Kappa agreement. Best agreement was found in Cobas 6000 followed by the Access2 then comes Architect.  Conclusions: All immunoassays can be used in routine 25(OH) D measurements, still some methods are better than others. A clinical laboratory must at least be aware of its method to avoid misinterpretation of results.