Prognostic significance of serial molecular annotation in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML)
Open accessAbstract
The implementation of next-generation sequencing (NGS) has influenced diagnostic, prognostic, and therapeutic decisions in myeloid malignancies. However, the clinical relevance of serial molecular annotation in patients with myelodysplastic syndrome (MDS) undergoing active treatment is unknown. MDS or secondary acute myeloid leukemia (sAML) patients who had at least two NGS assessments were identified. Outcomes according to mutation clearance (NGS-) on serial assessment were investigated. Univariate and multivariate Cox regression models were used to evaluate the prognostic impact of NGS trajectory on overall survival (OS). A total of 157 patients (MDS [n = 95]; sAML [n = 52]; CMML [n = 10]) were identified, with 93% of patients receiving treatment between NGS assessments. Magnitude of VAF delta from baseline was significantly associated with quality of response to treatment. Patients achieving NGS- had significantly improved OS compared to patients with mutation persistence (median OS not reached vs. 18.5 months; P = 0.002), which was confirmed in multivariate analysis (HR,0.14; 95%CI = 0.03-0.56; P = 0.0064). Serial TP53 VAF evaluation predicts outcomes with TP53 clearance representing an independent covariate for superior OS (HR,0.22; 95%CI = 0.05-0.99; P = 0.048). Collectively, our study highlights the clinical value of serial NGS during treatment and warrants prospective validation of NGS negativity as a biomarker for treatment outcome.
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The 5% cutoff was chosen based on prior data identifying TP53 VAF clearance to <5% as a robust predictor of OS by multivariate analysis.
“The 5% cutoff was also chosen based on prior data identifying TP53 VAF clearance to <5% as a robust predictor of OS by multivariate analysis.”
From Long‐term follow‐up and combined Phase 2 results of eprenetapopt and azacitidine in patients with <i>TP53</i> mutant MDS/AML (2025) · cites this paper as [30]
Our study validates prior work identifying TP53 VAF clearance to <5% as a predictor for OS in this molecular subgroup.
“notably validates prior work identifying TP53 VAF clearance to <5% as a predictor for OS in this molecular subgroup.”
From Long‐term follow‐up and combined Phase 2 results of eprenetapopt and azacitidine in patients with <i>TP53</i> mutant MDS/AML (2025) · cites this paper as [30]
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“17,30 Median OS for these patients was 26 months with a 2 ‐ year OS of 54%, which historically is around 20%.”
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- Authors
- Yun, S., Geyer, S. M., Komrokji, R. S., Al Ali, N. H., Song, J., Hussaini, M., Sweet, K. L., Lancet, J. E., List, A. F., Padron, E., & Sallman, D. A.
- Affiliations
- Moffitt Cancer Center (US)
- University of South Florida (US)
- Corresponding author
- Sallman, David A.
- ORCID
- Venue
- Leukemia
- Published
- 2020-07-29
- Volume
- 35
- Issue
- 4
- Pages
- 1145-1155
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- PMC
- PMC7854836
- OpenAlex
- W3045698646
- Cited by
- 49
- References
- 41
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 10 · 2023: 12 · 2022: 4 · 2021: 10 · 2020: 3
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Leukemia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (CA237627)
- ASH RTAF award USF GME grant
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Keywords
- myelodysplastic syndrome, secondary acute myeloid leukemia, chronic myelomonocytic leukemia, next-generation sequencing, variant allele frequency, TP53, overall survival, prognostic factors, treatment response monitoring
- MeSH terms
- Adult, Aged, Aged, 80 and over, Disease Susceptibility, Female, Humans, Male, Middle Aged, Mutation, Myelodysplastic Syndromes, Prognosis, Retrospective Studies, Biomarkers, Tumor, Leukemia, Myeloid, Acute, Survival Analysis, Computational Biology, Genetic Predisposition to Disease, Molecular Sequence Annotation, High-Throughput Nucleotide Sequencing
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