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arXiv · 2509.20402

Transformer-Based Hematological Malignancy Prediction from Peripheral Blood Smears in a Real-World Cohort

Muhammed Furkan Dasdelen·Ivan Kukuljan·Peter Lienemann·Fatih Ozlugedik·Ario Sadafi·Matthias Hehr·Karsten Spiekermann·Christian Pohlkamp·Carsten Marr
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Abstract

Peripheral blood smears remain a cornerstone in the diagnosis of hematological neoplasms, offering rapid and valuable insights that inform subsequent diagnostic steps. However, since neoplastic transformations typically arise in the bone marrow, they may not manifest as detectable aberrations in peripheral blood, presenting a diagnostic challenge. In this paper, we introduce cAItomorph, an explainable transformer-based AI model, trained to classify hematological malignancies based on peripheral blood cytomorphology. Our data comprises peripheral blood single-cell images from 6115 patients with diagnoses confirmed by cytomorphology, cytogenetics, molecular genetics, and immunophenotyping from bone marrow samples, and 495 healthy controls, eight coarse classes. cAItomorph leverages the DinoBloom hematology foundation model and aggregates image encodings via a transformer-based architecture into a single vector. It achieves an overall accuracy of 0.72 in eight disease classification, with F1 scores of 0.76 for acute leukemia, 0.80 for myeloproliferative neoplasms and 0.94 for healthy cases. The overall accuracy increases to 0.87 in top-2 predictions. cAItomorph achieves high sensitivity for acute leukemia cases in external test sets. By analyzing attention heads, we demonstrate clinically relevant cell-level attentions in both internal and external test sets. Moreover, our model's calibrated prediction probabilities reduce the false discovery rate from 13.5% to 8.7% without missing any acute leukemia cases, thereby decreasing the number of unnecessary bone marrow aspirations based on peripheral blood smears. This study highlights the potential of AI-assisted diagnostics in hematological malignancies, illustrating how models trained on real-world data could enhance diagnostic accuracy and reduce invasive procedures.

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Muhammed Furkan Dasdelen, Ivan Kukuljan, Peter Lienemann, Fatih Ozlugedik, Ario Sadafi, Matthias Hehr, Karsten Spiekermann, Christian Pohlkamp, Carsten Marr. 2025-09-23. Transformer-Based Hematological Malignancy Prediction from Peripheral Blood Smears in a Real-World Cohort. https://doi.org/10.1038/s41375-026-02934-1

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