Allogeneic HCT Outcomes in Patients With MDS and High-Risk Genetics

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In a genetic analysis from the Blood and Marrow Transplant Clinical Trials Network 1102 Study reported in the Journal of Clinical Oncology, Versluis et al found that allogeneic hematopoietic cell transplantation (HCT) improved overall survival compared with non-HCT treatment in patients with myelodysplastic syndromes (MDS) and TP53 mutations. In addition, patients with molecular International Prognostic Scoring System (IPSS-M) very high–risk disease without a TP53 mutation had improved survival when a HCT donor was available.

The study involved data from targeted sequencing in 309 study patients aged 50 to 75 years with IPSS intermediate-2 or high-risk MDS. Patients with TP53 mutations were classified as TP53-multihit if two alleles were altered (point mutation, deletion, or copy-neutral loss of heterozygosity). The impact of MDS genetics on the benefit of HCT was assessed in a donor vs no-donor fashion.

Key Findings

Distribution of genetic mutations was similar in the donor group (n = 229) and no-donor group (n = 80). TP53 (28% vs 29%, P = .89), ASXL1 (23% vs 29%, P = .37), and SRSF2 (16% vs 16%, P = .99) were the most common mutations.

Overall survival at 3 years was 52% ± 4% in patients without a TP53 mutation vs 21% ± 5% among those with a TP53 mutation (P < .001). Among patients with a TP53 mutation, 3-year overall survival did not differ between those with TP53–single-hit vs TP53-multihit alterations (22% ± 8% vs 20% ± 6%, P = .31).

In analysis with HCT as a time-dependent covariate, patients with a TP53 mutation who underwent HCT had improved 3-year overall survival vs those who received non-HCT treatment (23% ± 7% vs 11% ± 7%, P = .04). In analysis adjusting for covariates, the hazard ratio favoring HCT was 3.89 (95% confidence interval [CI] = 1.87–8.12, P < .001). Among patients with IPSS-M very high–risk disease without a TP53 mutation, 3-year overall survival was significantly improved among those with an available HCT donor vs those with no available donor (68% ± 10% vs 0% ± 12%, P = .001).

The investigators concluded, “HCT improved overall survival compared with non-HCT treatment in patients with TP53 mutations irrespective of TP53 allelic status. Patients with IPSS-M very high–risk [disease] without a TP53 mutation had favorable outcomes when a donor was available."

R. Coleman Lindsley, MD, PhD, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Heart, Lung, and Blood Institute and National Cancer Institute. For full disclosures of the study authors, visit

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