Prediction and recommendation by machine learning through repetitive internal validation for hepatic veno-occlusive disease/sinusoidal obstruction syndrome and early death after allogeneic hematopoietic cell transplantation

• Published in: Bone marrow transplantation (Basingstoke) 2022-04, Vol.57 (4), p.538-546
• Main Authors: Lee, Seungjoon, Lee, Eunsaem, Park, Sung-Soo, Park, Min Sue, Jung, Jaewoo, Min, Gi June, Park, Silvia, Lee, Sung-Eun, Cho, Byung-Sik, Eom, Ki-Seong, Kim, Yoo-Jin, Lee, Seok, Kim, Hee-Je, Min, Chang-Ki, Cho, Seok-Goo, Lee, Jong Wook, Hwang, Hyung Ju, Yoon, Jae-Ho
• Format: Article
• Language: English
• Subjects: 692/308/174; 692/700/459/1748; Busulfan; Busulfan - therapeutic use; Cell Biology; Cell death; Death; Dosage; Health risks; Health services; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Hepatic Veno-Occlusive Disease - chemically induced; Humans; Internal Medicine; Learning algorithms; Liver diseases; Machine Learning; Medicine; Medicine & Public Health; Mortality; Public Health; Recommender systems; Reproducibility of Results; Risk analysis; Risk factors; Sine waves; Statistical methods; Stem cell transplantation; Stem Cells; Subgroups; Transplantation; Transplants; Transplants & implants; Vascular Diseases - chemically induced; Veno-occlusive disease
• ISSN: 0268-3369; 1476-5365; 1476-5365
• DOI: 10.1038/s41409-022-01583-z

Using traditional statistical methods, we previously analyzed the risk factors and treatment outcomes of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after allogeneic hematopoietic cell transplantation. Within the same cohort, we applied machine learning to create prediction and recommendation models. We analyzed 2572 transplants using eXtreme Gradient Boosting (XGBoost) to predict post-transplant VOD/SOS and early death. Using the XGBoost and SHapley Additive exPlanations (SHAP), we found influential factors and devised recommendation models, which were internally verified by repetitive ten-fold cross-validation. SHAP values suggested that gender, busulfan dosage, age, forced expiratory volume, and Disease Risk Index were significant factors for VOD/SOS. The areas under the receiver operating characteristic curves and the areas under the precision-recall curve of the models were 0.740, 0.144 for all VOD/SOS, 0.793, 0.793 for severe to very severe VOD/SOS, and 0.746, 0.304 for early death. According to our single feature recommendation, following the busulfan dosage was the most effective for preventing VOD/SOS. The recommendation method for six adjustable feature sets was also validated, and a subgroup corresponding to five to six features showed significant preventive power for VOD/SOS and early death. Our personalized treatment set recommendation showed reproducibility in repetitive internal validation, but large external cohorts should prospectively validate our model.