Donor mitochondrial DNA variants found to impact outcomes in MDS after transplantation

Mitochondrial DNA (mtDNA) variants in transplant donors, including unrelated donors, significantly impact the outcomes of allogeneic hematopoietic cell transplantation for patients with myelodysplastic syndromes (MDS), according to a study.

Researchers analyzed whole-genome sequencing data from 494 donors matched to patients with MDS enrolled in the Center for International Blood and Marrow Transplant Research. They found 1,825 mtDNA variants, including 67 potentially pathogenic mutations. Key variants in the MT-CYB and MT-ND5 genes were identified as independent predictors of transplant outcomes, such as overall survival, relapse, and transplant-related mortality.

The study found that integrating donor mtDNA variants into the International Prognostic Scoring System-Revised enhanced the ability to predict patients with MDS outcomes. Combining mtDNA variants with clinical factors like donor age and HLA-matching also improved donor selection. It helped identify both “suboptimal” younger HLA-well-matched and “optimal” older, partially or mismatched donors.

Reference

Dong J, Arsang-Jang S, Zhang T, et al. Prognostic impact of donor mitochondrial genomic variants in myelodysplastic neoplasms after stem-cell transplantation. J Hematol Oncol. 2024;17(1):104. doi: 10.1186/s13045-024-01622-w. PMID: 39497145; PMCID: PMC11533675.