Evaluation of a Machine Learning-Based Prognostic Model for Unrelated Hematopoietic Cell Transplantation Donor Selection.

Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
Published Date:

Abstract

The survival of patients undergoing hematopoietic cell transplantation (HCT) from unrelated donors for acute leukemia exhibits considerable variation, even after stringent genetic matching. To improve the donor selection process, we attempted to create an algorithm to quantify the likelihood of survival to 5 years after unrelated donor HCT for acute leukemia, based on the clinical characteristics of the donor selected. All standard clinical variables were included in the model, which also included average leukocyte telomere length of the donor based on its association with recipient survival in severe aplastic anemia, and links to multiple malignancies. We developed a multivariate classifier that assigned a Preferred or NotPreferred label to each prospective donor based on the survival of the recipient. In a previous analysis using a resampling method, recipients with donors labeled Preferred experienced clinically compelling better survival compared with those labeled NotPreferred by the test. However, in a pivotal validation study in an independent cohort of 522 patients, the overall survival of the Preferred and NotPreferred donor groups was not significantly different. Although machine learning approaches have successfully modeled other biological phenomena and have led to accurate predictive models, our attempt to predict HCT outcomes after unrelated donor transplantation was not successful.

Authors

  • Ljubomir Buturovic
    Clinical Persona Inc., East Palo Alto, California. Electronic address: ljubomir@clinicalpersona.com.
  • Jason Shelton
    Telomere Diagnostics, Menlo Park, California.
  • Stephen R Spellman
    Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
  • Tao Wang
    Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Lyssa Friedman
    Telomere Diagnostics, Menlo Park, California.
  • David Loftus
    Telomere Diagnostics, Menlo Park, California.
  • Lyndal Hesterberg
    Telomere Diagnostics, Menlo Park, California.
  • Todd Woodring
    Telomere Diagnostics, Menlo Park, California.
  • Katharina Fleischhauer
    Institute for Experimental Cellular Therapy, University Hospital Essen, Germany.
  • Katharine C Hsu
    Memorial Hospital Research Laboratories, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Michael R Verneris
    Children's blood and bone marrow diseases, Department of pediatrics, University of Colorado-Denver, Denver, Colorado.
  • Mike Haagenson
    Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
  • Stephanie J Lee
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington.