May AlMoshary

Background: MicroRNAs (miRNAs) are small molecules that regulate gene expression and may influence the severity and progression of rare hereditary anemias. Understanding their role can support the development of targeted treatments. To our knowledge, this multicenter longitudinal cohort is among the first to characterize miRNA profiles—particularly miR-155—in pediatric patients with rare hereditary anemias presenting with sepsis, and to report exploratory translational observations relevant to gene-based modulation frameworks. Objective: This study aimed to profile miRNA expression in septic patients with rare hereditary anemias and evaluate associations with disease severity, progression, and response to gene therapy. Methods: This prospective cohort study was conducted at five medical centers in the United States and Saudi Arabia, enrolling 400 participants— 200 patients with rare hereditary anemias and 200 healthy controls. Blood samples were analyzed using high-throughput sequencing and advanced bioinformatics. Randomization and blinding procedures were applied to ensure data integrity and minimize bias. Results: At baseline enrollment during septic presentation, patients exhibited significantly lower mean hemoglobin levels compared to controls (9.2 g/dL vs 12.5 g/dL, p < 0.001). Patients with hereditary anemia had significantly lower average hemoglobin levels (9.2 g/dL) compared to controls (12.5 g/dL, p < 0.001) and higher reticulocyte counts. miR-155 was upregulated 2.5-fold in affected patients (p < 0.01). These patients required an average of six transfusions annually, compared to none in the control group (p < 0.001). Thirty-five percent of patients experienced worsening anemia over time. ROC curve analysis demonstrated miR-155 as a strong diagnostic biomarker, with 85% sensitivity, 90% specificity, and an AUC of 0.97. Conclusion: miR-155 plays a key role in the progression of rare hereditary anemias in septic patients and shows potential as both a diagnostic and therapeutic target. These findings highlight opportunities for personalized, miRNA-based therapies to improve disease management and patient outcomes. No clinically evident severe vector-related adverse events were observed during follow-up. Clinical Trial Number: ECRIN-EU-TRIAL-2025-002739.

Background Relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) presents major therapeutic difficulties that need for creative solutions. Although their respective processes are different, CAR T-cell therapy and Blinatumomab have yet unknown relative efficacy. Objectives Guiding optimum treatment choice in high-risk DLBCL patients, this research intends to evaluate effectiveness, safety, progression-free survival (PFS), and complete remission rates (CRR) comparing CAR T-cell therapy and Blinatumomab. Methods This prospective cohort research compares, in 400 patients with relapsed/refractory Diffuse Large B-Cell Lymphoma (DLBCL) across five high-volume cancer centres in Saudi Arabia, the relative effectiveness and safety of CAR T-cell treatment with Blinatumomab. Stratified by illness severity and age, patients—n = 200 per group—have randomised therapy allocation. While Blinatumomab entails continuous intravenous infusion in six-week cycles, CAR T-cell treatment consists in lymphodepleting chemotherapy, T-cell collecting, genetic alteration, and reinfusion. Among the main results are remission rates, general survival, and progression-free survival. Strong statistical analysis, careful data collecting from electronic health records, and blinded outcome evaluations guarantee validity and repeatability of findings. Results Examining 400 patients with relapsed/refractory DLBCL (200 CAR T-cell, 200 Blinatumomab) matched for age (mean: 61.4 years, SD ± 8.9), gender (57% vs. 55% male), BMI (27.6 vs. 27.9 kg/m²), and comorbidities, this study found With a greater complete remission rate (58% vs. 34%) and longer median progression-free survival (16.8 vs. 9.4 months, CAR T-cell treatment produced better results. But it caused severe CRS (78% vs. 48%), neurotoxicity (52% vs. 38%), and extended cytopenias (neutropenia: 62% vs. 44%). Though less hazardous, blinatumomab needed several cycles to be continuously effective. With sustained remissions (42% PFS at 24 months vs 18%), CAR T-cell treatment clearly has long-term benefits. Balancing effectiveness, toxicity, and patient-specific dangers, personalised therapy selection is crucial. Conclusion Higher complete remission rates and longer PFS than Blinatumomab allow CAR T-cell treatment to offer better long-term disease management in relapsed/refractory DLBCL. Its increased toxicity load, however, calls for extensive care; Blinatumomab provides a less toxic, temporary substitute needing several cycles for long-term effectiveness.

Objectives: To evaluate the outcomes (relapse and mortality rate) and response of the bone marrow in early stages after combination chemotherapy in patients with T-cell Acute Lymphoblastic Leukemia (T-ALL). Methods: A descriptive cross-sectional study was conducted at King Fahad Medical City, from January 2021 to December 2022, to evaluate bone marrow findings at the time of diagnosis and post-chemotherapy in 26 patients diagnosed with T-ALL. The study included all patients diagnosed with T-ALL of any age group during the study period. The patients’ bone marrows were examined at 0 days of treatment (diagnosis work-up), followed by examination at day 15 post induction therapy, and day 30 after treatment. Results: In this study, 26 cases of T-lymphoblastic leukemia were analyzed. The mean age at diagnosis was 15.69±14.28 years, and eight cases had central nervous system involvement. The majority of cases (88.5%) were positive for Cytoplasmic-CD3 and CD7. Positive findings by fluorescence in situ hybridization (FISH) were: T cell receptor (TCR) α/δ in 6 (23.1%) of the patients, CDNK2A/CEP9 in five (19.2%), and TRCB in one (3.8%). Examination of the bone marrow on day 15 revealed a decrease in blasts to ≤1% in nine patients, and to ≤1% in 19 patients on day 30 post-therapy. Relapse was recorded in five (19.23%) patients. Three (11.53%) patients did not survive during treatment, of which two were <10 years old. The relapse rate for T-ALL was 19.23%, with an overall survival rate of about 64%. The overall mortality rate was 11.53%. Conclusion: The relapse rate for T-ALL in our study was approximately 19%, but the mortality rate was 11.5%. A substantial decrease in blast percentages was observed, suggesting a favorable initial reaction of the bone marrow to the combined chemotherapy. This suggests that the use of aggressive and more effective chemotherapy has led to better outcomes. doi: https://doi.org/10.12669/pjms.40.5.7584 How to cite this: AlMoshary M, Altahan SM, Alswayyed AF. Early response and outcomes of bone marrow to chemotherapy in T-Cell Acute Lymphoblastic Leukemia. Pak J Med Sci. 2024;40(5):979-984. doi: https://doi.org/10.12669/pjms.40.5.7584 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Venous thromboembolism (VTE) is a common condition that can recur, leading to multiple therapeutic strategies to prevent it. The aim of this study was to explore the clinical efficacy of VTE management in Saudi Arabian hospitals and to gain insights into patient outcomes. A retrospective single-center study was conducted that retrieved the data of all patients with VTE registered from January 2015 to December 2017. Patients of all age groups were included if they attended the thrombosis clinic at KFMC during the data collection period. The study analyzed the various therapeutic strategies used for VTE and their effect on patient outcomes. The results showed that 14.6% of the patients had provoked VTE, with a higher incidence among females and younger patients. The most commonly prescribed treatment was combination therapy, followed by warfarin, oral anticoagulants, and factor Xa inhibitor. Despite being prescribed treatment, 74.9% of the patients experienced recurrence of VTE. There was no associated risk factor for recurrence in 79.9% of the patients. Thrombolytic therapy and catheter-directed thrombolysis were found to be associated with a lower risk of VTE recurrence, while anticoagulation therapy, including oral anticoagulants, was associated with a higher risk. Vitamin K antagonist (warfarin) and factor Xa inhibitor (rivaroxaban) had a significant positive association with VTE recurrence, while the use of a direct thrombin inhibitor (dabigatran) showed a lower risk, but it was not statistically significant. The results of the study highlight the need for further research to determine the most effective therapeutic strategy for VTE management in Saudi Arabian hospitals. The findings also suggest that anticoagulation therapy, including oral anticoagulants, may increase the risk of VTE recurrence, while thrombolytic therapy and catheter-directed thrombolysis may lower the risk.