Abstract
Background/Objectives: Acute Lymphoblastic Leukemia (ALL) poses significant diagnostic challenges due to its ambiguous symptoms and the limitations of conventional methods like bone marrow biopsies and flow cytometry, which are invasive, costly, and time-intensive. Methods: This study introduces Neuro-Bridge-X, a novel neuro-symbolic hybrid model designed for automated, explainable ALL diagnosis using peripheral blood smear (PBS) images. Leveraging two comprehensive datasets, ALL Image (3256 images from 89 patients) and C-NMC (15,135 images from 118 patients), the model integrates deep morphological feature extraction, vision transformer-based contextual encoding, fuzzy logic-inspired reasoning, and adaptive explainability. To address class imbalance, advanced data augmentation techniques were applied, ensuring equitable representation across benign and leukemic classes. The proposed framework was evaluated through 5-fold cross-validation and fixed train-test splits, employing Nadam, SGD, and Fractional RAdam optimizers. Results: Results demonstrate exceptional performance, with SGD achieving near-perfect accuracy (1.0000 on ALL, 0.9715 on C-NMC) and robust generalization, while Fractional RAdam closely followed (0.9975 on ALL, 0.9656 on C-NMC). Nadam, however, exhibited inconsistent convergence, particularly on C-NMC (0.5002 accuracy). A Meta-XAI controller enhances interpretability by dynamically selecting optimal explanation strategies (Grad-CAM, SHAP, Integrated Gradients, LIME), ensuring clinically relevant insights into model decisions. Conclusions: Visualizations confirm that SGD and RAdam models focus on morphologically critical features, such as leukocyte nuclei, while Nadam struggles with spurious attributions. Neuro-Bridge-X offers a scalable, interpretable solution for ALL diagnosis, with potential to enhance clinical workflows and diagnostic precision in oncology.