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

Abstract

PURPOSE 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. MATERIALS AND METHODS 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 ( S t = 52) and a validation set ( S v = 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. RESULTS The risk score was associated with RFS in S t (hazard ratio = 2.38; 95% CI, 1.4 to 3.95; P = .0008) and S v (hazard ratio = 1.57; 95% CI, 1.01 to 2.45; P = .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 S v. All the relevant code is available at GitHub. CONCLUSION The texture features extracted from chromatin patterns of myeloblasts can predict post-HCT relapse and prognosticate RFS of patients with AML/MDS.