Machine Learning to Predict Risk of Relapse Using Cytologic Image Markers in Patients With Acute Myeloid Leukemia Posthematopoietic Cell Transplantation.

Abstract

Allogenic hematopoietic stem-cell transplant (HCT) is a curative therapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Relapse post-HCT is the most common cause of treatment failure and is associated with a poor prognosis. Pathologist-based visual assessment of aspirate images and the manual myeloblast counting have shown to be predictive of relapse post-HCT. However, this approach is time-intensive and subjective. The premise of this study was to explore whether computer-extracted morphology and texture features from myeloblasts' chromatin patterns could help predict relapse and prognosticate relapse-free survival (RFS) after HCT. In this study, Wright-Giemsa-stained post-HCT aspirate images were collected from 92 patients with AML/MDS who were randomly assigned into a training set (<i>S</i>_<i>t</i> = 52) and a validation set (<i>S</i>_<i>v</i> = 40). First, a deep learning-based model was developed to segment myeloblasts. A total of 214 texture and shape descriptors were then extracted from the segmented myeloblasts on aspirate slide images. A risk score on the basis of texture features of myeloblast chromatin patterns was generated by using the least absolute shrinkage and selection operator with a Cox regression model. The risk score was associated with RFS in <i>S</i>_<i>t</i> (hazard ratio = 2.38; 95% CI, 1.4 to 3.95; <i>P</i> = .0008) and <i>S</i>_<i>v</i> (hazard ratio = 1.57; 95% CI, 1.01 to 2.45; <i>P</i> = .044). We also demonstrate that this resulting signature was predictive of AML relapse with an area under the receiver operating characteristic curve of 0.71 within <i>S</i>_<i>v</i>. All the relevant code is available at GitHub. The texture features extracted from chromatin patterns of myeloblasts can predict post-HCT relapse and prognosticate RFS of patients with AML/MDS.