A Leakage-Aware Comparative Benchmark of Machine Learning, Deep Learning, and Transformer Models for Reliable Leukemia Detection

Leukemia cell image classification is challenged by real-world domain shifts from acquisition, staining, illumination, and site protocols, causing single-dataset models to generalize poorly in real clinical scenarios. This work presents a robust framework for leukemia classification across multiple heterogeneous datasets using a two-stage pipeline with a pretrained vision foundation model. Stage 1 performs binary classification (leukemia vs. non-leukemia) and is trained using 122,167 single-cell images. Stage 2 is conditionally applied to Stage 1 positives to perform subtype classification into Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML), trained using 69,400 single-cell images. Labels are harmonized across five heterogeneous datasets to enable cross-dataset training, and performance is evaluated on a held-out dataset protocol to assess domain-shift generalization. Within this pipeline, three encoders are benchmarked (DinoBloom, pretrained on single-cell images; BiomedCLIP, pretrained on biomedical data; and CLIP as a general-purpose model) under linear probing, Low-Rank Adaptation (LoRA), and a Retrieval-Augmented Classification (RAC) module that retrieves the top-k most similar cell images to provide cytomorphological grounding. The objective is to quantify how much domain-specific pretraining contributes to performance under domain shift, and whether cost-effective adaptation and retrieval can be a viable alternative to expensive domain-specialized pretraining. The held-out protocol additionally serves as a diagnostic tool, revealing when classification performance is attributable to dataset-specific artifacts rather than to cytomorphological features.

Bone marrow smear review remains important for acute myeloid leukemia (AML) assessment, but manual single-cell interpretation is labor-intensive and patient-level diagnosis requires aggregation of many cellular observations. We present a cell-to-patient deep learning pipeline for AML-assisted diagnosis from bone marrow smear images. The study included 258 patients from six anonymized centers, including a main cohort of 169 patients from Centers 1-3 and an external validation cohort of 89 patients from Centers 4-6. A 16-category cell annotation vocabulary was used to describe the global cellular composition, including granulocytic, monocytic, erythroid, lymphoid, eosinophilic, and other cells. Rather than identifying strict AML blasts or leukemic blasts, the model targets an expert-defined composite category termed Composite Blast-like Cells (CBLC), comprising N, N1, M, M1, R, R1, J, and J1 according to the project-wide morphological standard. A fixed YOLO-based segmentation module detected cells, predicted contours were matched to expert polygon annotations by contour IoU, and standardized single-cell crops were generated. An EfficientNet-B0 classifier was trained through a two-stage GT-to-YOLO and YOLO-to-YOLO strategy with class-imbalance correction, center-border regularization, and morphology-assisted supervision. Cell-level predictions were aggregated into patient-level CBLC ratios for AML-oriented diagnostic support. The pipeline achieved stable internal validation and maintained external generalization, with ensemble weighted F1-scores of 0.9076, 0.8696, and 0.9124 on Centers 4, 5, and 6, respectively.

Automated analysis of peripheral blood smears for Acute Lymphoblastic Leukemia (ALL) is hindered by low contrast and substantial variability in cytoplasmic appearance, which complicate conventional membrane-based segmentation. We found that many recent approaches rely on heavy neural architectures and extensive training, but still struggle to generalize across staining and acquisition variability. To address these limitations, we propose the Perinuclear Ring-based Image Segmentation Method (PRISM), which replaces explicit cytoplasmic delineation with adaptive concentric zones constructed around the nucleus. These perinuclear regions enable the extraction of robust cytoplasmic descriptors by integrating color information with texture statistics derived from grey-level co-occurrence patterns, without requiring accurate cell-boundary detection. A calibrated stacking ensemble of traditional classifiers leverages these descriptors to achieve a high performance, with an accuracy of 98.46% and a precision-recall AUC of 0.9937.