Limited Contribution of Donor Characteristics to One-Year Survival After Hematopoietic Stem Cell Transplantation

Sapir Israeli, Martin Maiers, Yoram Louzoun

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

A large number of association studies have related donor characteristics to survival after bone marrow transplantation, for leukemia in general and specifically for acute myeloid leukemia (AML) patients. However, population-based differences often do not hold at the single transplant level. We test whether transplantation outcomes can be predicted at the single-patient level and whether such predictions can be used to better choose donors. The analysis was performed on a mixture of different diseases or with AML only, and with either patient and donor information or donor information only. We analyzed 3671 8-of-8 HLA-matched AML donor-recipient pairs and tested whether the outcome, including 1-year total and event-free survival, can be predicted from patient and donor-related factors. We used multiple machine learning and survival analysis methods. The best method is a fully connected neural network. Multiple outcomes can be predicted, with area under the specificity-sensitivity curve (AUC) values between 0.54 and 0.67 for the different outcomes. The patient age has a strong impact on prediction. However, for a given patient, when only donor or transplant information is used, limited prediction accuracy of 0.54 to 0.56 AUC for event-free survival and survival is obtained. Graft-versus-host disease and rejection after 1 year have slightly higher AUC values of around 0.59, whereas the relapse prediction accuracy was random. All donors’ characteristics have a limited influence on the quality of hematopoietic stem cell transplantation for fully matched donors. Many factors with a population effect on survival have a very limited effect when combined with all other factors in a single-donor predictive model.

Original languageEnglish
Pages (from-to)843.e1-843.e6
JournalTransplantation and Cellular Therapy
Volume28
Issue number12
DOIs
StatePublished - Dec 2022

Bibliographical note

Publisher Copyright:
© 2022 The American Society for Transplantation and Cellular Therapy

Funding

Financial disclosure: Supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research; Additional federal support is provided by R01AI128775, R01HL130388, and BARDA. Support is also provided by Be the Match Foundation, the Medical College of Wisconsin the National Marrow Donor Program, and from the following commercial entities: Actinium Pharmaceuticals, Inc.; Adienne SA; Allovir, Inc.; Amgen, Inc.; Angiocrine Bioscience; Astellas Pharma US; Bluebird Bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co. Ltd.; ExcellThera; Fate Therapeutics; Gamida-Cell, Ltd.; Genentech Inc; Incyte Corporation; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc.; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Stemcyte; Takeda Pharma; Vor Biopharma; Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. Financial disclosure: See Acknowledgments on page XXXX. Financial disclosure: Supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID) ; HHSH250201700006C from the Health Resources and Services Administration (HRSA) ; and N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research; Additional federal support is provided by R01AI128775, R01HL130388, and BARDA. Support is also provided by Be the Match Foundation, the Medical College of Wisconsin the National Marrow Donor Program, and from the following commercial entities: Actinium Pharmaceuticals, Inc.; Adienne SA; Allovir, Inc.; Amgen, Inc.; Angiocrine Bioscience; Astellas Pharma US; Bluebird Bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; ExcellThera; Fate Therapeutics; Gamida-Cell, Ltd.; Genentech Inc; Incyte Corporation; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc.; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Stemcyte; Takeda Pharma; Vor Biopharma; Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government.

FundersFunder number
Allovir, Inc.
Fate Therapeutics
Gilead company
Magenta Therapeutics
Match Foundation
U.S. Government
National Institutes of Health
U.S. Department of Defense
Office of Naval ResearchR01AI128775
National Heart, Lung, and Blood InstituteR01HL130388
National Cancer InstituteU24CA076518
National Institute of Allergy and Infectious DiseasesHHSH250201700006C
Health Resources and Services AdministrationN00014-20-1-2832, N00014-20-1-2705
Amgen
Astellas Pharma US
U.S. Public Health Service
CSL Behring
U.S. Navy
Merck Sharp and Dohme
Biomedical Advanced Research and Development Authority
Angiocrine Bioscience
Incyte
Legend Biotech
Daiichi-Sankyo
Kyowa Hakko Kirin
CytoSen Therapeutics
Daiichi Sankyo Europe

    Keywords

    • EFS
    • HSCT
    • Survival analysis

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