Identification of high-risk amino-acid substitutions in hematopoietic cell transplantation: a challenging task. Bone Marrow Transplant 2016 Oct;51(10):1342-1349
Date
05/24/2016Pubmed ID
27214075Pubmed Central ID
PMC5052106DOI
10.1038/bmt.2016.142Scopus ID
2-s2.0-84969785210 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
Allogeneic hematopoietic cell transplantation (HCT) offers the potential to cure hematologic malignancies. In the absence of an HLA-matched donor, HLA mismatched unrelated donors may be used, although risks of GvHD and treatment-related mortality (TRM) are higher. Identification and avoidance of amino-acid substitution and position types (AASPT) conferring higher risks of TRM and GvHD would potentially improve the success of transplantation from single HLA mismatched unrelated donors. Using random forest and logistic regression analyses, we identified 19 AASPT associated with greater risks for at least one adverse transplant outcome: grade III-IV acute GvHD, TRM, lower disease-free survival or worse overall survival relative to HLA-matched unrelated donors and to other AASPT. When tested in an independent validation cohort of 3530 patients, none of the AASPT from the training set were validated as high risk, however. Review of the literature shows that failure to validate original observations is the rule and not the exception in immunobiology and emphasizes the importance of independent validation before clinical application. Our current data do not support avoiding any specific class I AASPT for unrelated donors. Additional studies should be performed to fully understand the role of AASPT in HCT outcomes.
Author List
Marino SR, Lee SM, Binkowski TA, Wang T, Haagenson M, Wang HL, Maiers M, Spellman S, van Besien K, Lee SJ, Karrison T, Artz AAuthor
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Amino Acid Substitution
Child
Child, Preschool
Hematopoietic Stem Cell Transplantation
Histocompatibility
Humans
Infant
Logistic Models
Middle Aged
Risk Assessment
Treatment Outcome
Unrelated Donors
Unsupervised Machine Learning
Young Adult