Novel Genomic Biomarkers Improve Post-Hematopoietic Cell Transplantation Relapse Risk Stratification for Patients With Myelodysplastic Syndromes. JCO Precis Oncol 2026 Jan;10:e2500140
Date
01/23/2026Pubmed ID
41576307Pubmed Central ID
PMC12932076DOI
10.1200/PO-25-00140Scopus ID
2-s2.0-105035092780 (requires institutional sign-in at Scopus site)Abstract
PURPOSE: Hematopoietic cell transplantation (HCT) is considered the only curative treatment for patients with myelodysplastic syndrome (MDS), with disease relapse (REL) as the major cause of post-HCT failure. We aimed to conduct a comprehensive genomic screening of prognostic biomarkers associated with post-HCT disease relapse.
METHODS: In this retrospective, cohort study, we analyzed whole-genome sequencing data from 494 non-Hispanic White patients with MDS who received HCT in the Center for International Blood and Marrow Transplant Research network. Genomic prognostic biomarkers were determined by cause-specific Cox regression multivariable models, with additional sensitivity analyses on unrelated transplant subcohorts and different competing outcomes. Their clinical significance on post-HCT risk stratifications was further evaluated via random survival forest models with optimism-bias adjusted bootstrap procedure.
RESULTS: Ten novel genomic biomarkers associated with relapse were identified, including somatic mutations in two genes (HNRNPA3 and TENM2), one locus (HSPC324) with a burden of rare germline single-nucleotide variants (SNVs), six loci harboring common SNVs, and one region harboring a structural variant (SV). For prognostic performance comparisons, the combined model that included these novel genomic biomarkers showed significant improvement of concordance indices (0.747 [95% CI, 0.705 to 0.786]) for predicting post-HCT disease relapse, compared with 0.547 (95% CI, 0.503 to 0.595) in the baseline model (Revised International Prognostic Scoring System [IPSS-R] + hypomethylating agents + graft-versus-host disease prophylaxis). Especially, the combined model showed superior risk stratifications for low or intermediate IPSS-R MDS patients with divergent post-HCT outcomes.
CONCLUSION: Our results suggest that SNVs and SVs beyond recurrent somatic mutations and cytogenetic abnormalities may play important roles in determining post-HCT relapse risk stratification in patients with MDS.
Author List
Zhang T, Auer PL, Dong J, Chen Z, Spellman SR, Saber W, Bolon YTAuthors
Paul L. Auer PhD Professor in the Data Science Institute department at Medical College of WisconsinJing Dong PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdultAged
Female
Genomics
Hematopoietic Stem Cell Transplantation
Humans
Male
Middle Aged
Myelodysplastic Syndromes
Prognosis
Recurrence
Retrospective Studies
Risk Assessment
