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Distinguishing Reactive Lymphocytes From Blasts Using Fractal Chromatin Patterns
Abigail Gordhamer1, Henry Tullis1, Ryan Cordner1
1Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, USA.
International Journal of Laboratory Hematology
|August 16, 2025
Summary
Differentiating reactive lymphocytes (RLs) and blasts is challenging. This study introduces a novel method using fractal chromatin patterns to accurately distinguish these cells, aiding clinical hematology diagnostics.
Area of Science:
- Hematology
- Computational Biology
- Image Analysis
Background:
- Reactive lymphocytes (RLs) and blasts are morphologically similar and difficult to differentiate in peripheral blood smears.
- Distinguishing RLs from blasts is critical as they are associated with different diseases, prognoses, and treatments.
- Current morphological methods lack definitive accuracy in distinguishing these cell types.
Purpose of the Study:
- To develop and validate a computational method for differentiating reactive lymphocytes (RLs) and blasts.
- To assess the efficacy of fractal chromatin pattern quantification in distinguishing between RLs and blasts.
- To explore the potential clinical utility of this algorithm in hematology laboratories.
Main Methods:
- Nuclei from white blood cell images were isolated for fractal pattern quantification using TWOMBLI software.
- Machine learning models (random forest, k-nearest neighbors) were trained and tested using cross-validation.
- Performance metrics including accuracy, AUC, precision, specificity, and sensitivity were evaluated.
Main Results:
- The developed classification algorithm achieved an average accuracy of 84.2% and an AUC of 0.844 in distinguishing RLs and blast subtypes.
- All models demonstrated an area under the curve (AUC) greater than 0.815 on the testing set.
- Principal Component Analysis (PCA) identified two key components explaining 50% of the data variance.
Conclusions:
- Fractal chromatin pattern analysis provides an effective means to distinguish between reactive lymphocytes and blasts.
- The proposed classification algorithm shows promise for assisting clinicians in differentiating these critical cell types in peripheral blood smears.
- This approach may enhance diagnostic accuracy and improve patient management in clinical hematology.

