title: Multiple single-nucleotide polymorphism-based risk model for clinical outcomes after allogeneic stem-cell transplantation, especially for acute graft-versus-host disease.
abstract: BACKGROUND
  We aimed to develop multiple single-nucleotide polymorphism (SNP)-based risk models associated with the risk of transplant outcomes including graft-versus-host disease (GVHD).
  
  
  METHODS
  The study evaluated 259 SNPs in 53 genes in 394 pairs of donors and recipients. In a discovery set (n=307 receiving related donor transplantation), overall survival, relapse-free survival (RFS), nonrelapse mortality, and acute or chronic GVHD were evaluated.
  
  
  RESULTS
  Eight recipients' SNPs of IL2, IL6R, FAS, EDN1, TGFB1, and NFKBIA genes and 12 donors' SNPs of NOS1, IL1B, TGFB2, NOD2/CARD15, TNFRII, IL1R1, and FCGR2A genes were identified in univariate analyses. Risk models were generated using significant clinical variables and genetic SNP markers after filtering out through multivariate analyses. Then, we divided patients into four quartiles (25%, Q) according to their risks. The final models stratified patients into low-risk (Q1), moderate-risk (Q2, Q3), and high-risk (Q4) groups in terms of overall survival (P<0.0001), RFS (P<0.0001), nonrelapse mortality (P=0.0043), and acute GVHD (P<0.0001), but not for chronic GVHD (P=0.763). External validation was performed in 87 transplant pairs that received matched unrelated donor transplantation, especially for RFS (P=0.016) and acute GVHD (P=0.027).
  
  
  CONCLUSIONS
  Risk models can improve prognostic stratification of patients according to their risk for transplant outcome.
authors.affiliation: Allogeneic Blood and Marrow Transplantation Program, Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada. drkiim@medimail.co.kr
authors.forename: Dennis Dong Hwan
authors.initials: DD
authors.lastname: Kim
authors.forename: Jina
authors.initials: J
authors.lastname: Yun
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Won
authors.forename: Lu
authors.initials: L
authors.lastname: Cheng
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Jieun
authors.initials: J
authors.lastname: Uhm
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
authors.forename: John
authors.initials: J
authors.lastname: Kuruvilla
authors.forename: Hans A
authors.initials: HA
authors.lastname: Messner
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
mesh_terms: D000208:Acute Disease; D000328:Adult; D002908:Chronic Disease; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality*; D014184:Transplantation, Homologous