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Cited by 35Acute Myeloid Leukemia ResearchHematopoietic Stem Cell TransplantationChronic Myeloid Leukemia Treatments

TP53-mutant variant allele frequency and cytogenetics determine prognostic groups in MDS/AML for transplantation

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Lontos, Konstantinos, Saliba, Rima M., Kanagal-Shamanna, Rashmi, Özcan, Gonca, Ramdial, Jeremy, Chen, George, Kadia, Tapan, Short, Nicholas James +8 more·2025·Blood Advances
DOI 10.1182/bloodadvances.2024014499PMC PMC12198588
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Abstract

Results after hematopoietic stem cell transplantation (HSCT) for TP53-mutated myeloid malignancies are disappointing. Several HSCT centers decline to perform HSCT for patients with TP53 mutation because of poor outcomes. In this study, we analyzed 240 patients with TP53-mutated myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who underwent HSCT. We aimed to identify the patients who benefit most from HSCT. The primary outcome was progression-free survival (PFS). Of the cohort, 52% had AML and the median age was 62 years. AML and MDS outcomes were similar. We identified several favorable prognostic factors for PFS, including absence of complex cytogenetics/5q deletion/7q deletion, a lower variant allele frequency (VAF), a monohit status, and use of a matched-related donor. Using classification and regression tree analysis, we identified VAF and cytogenetics as the 2 most important prognostic factors. Patients with TP53mut VAF ≥ 50% had a 2-year PFS of 3%, and patients with TP53mut VAF < 50% and complex/5q/7q cytogenetic abnormalities had 2-year PFS of 22%. Patients with TP53mut VAF < 50% and without complex/5q/7q cytogenetics had 2-year PFS of 60%. These data inform clinical practice and help patients decide whether to pursue HSCT.

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  • In that cohort, 2-year PFS was 3% for patients with VAF ≥ 50%; 22% for VAF < 50% + CK [±5/7 abnormalities]; 60% if VAF < 50% and absence of CK.

    “(3% for patients with VAF ≥ 50%; 22% for VAF < 50% + CK [±5/7 abnormalities]; 60% if VAF < 50% and absence of CK).”

    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 [45]

    The Results (HSCT outcomes) report the stated 2-year PFS values of 3%, 22%, and 60%. The cytogenetic groups are less accurately described: the 22% group had complex cytogenetics OR 5q/7q abnormalities, while the 60% group had neither complex cytogenetics NOR 5q/7q abnormalities. Absence of complex karyotype alone does not define the 60% group. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • A recent large cohort of 240 patients identified cytogenetic complexity and VAF as the strongest predictive factors of 2-year PFS.

    “a recent large cohort of 240 patients identified both cytogenetic complexity and VAF to be the strongest predictive factors of 2‐year PFS”

    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 [45]

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Authors
Lontos, K., Saliba, R. M., Kanagal-Shamanna, R., Özcan, G., Ramdial, J., Chen, G., Kadia, T., Short, N. J., Daver, N. G., Kantarjian, H., Marin, D., Kebriaei, P., Popat, U., Champlin, R., Shpall, E., & Oran, B.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • 2Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
  • 3Department of Hematology Oncology, National Institutes of Health, Bethesda, MD
Corresponding author
Oran, Betül
ORCID
Venue
Blood Advances
Publisher
American Society of Hematology
Published
2025-06-10
Volume
9
Issue
11
Pages
2845-2854
ISSN
  • 2473-9529 (ISSN-L)
  • 2473-9537
DOI
10.1182/bloodadvances.2024014499
PMC
PMC12198588
OpenAlex
W4406798090
Cited by
35
References
26
Citations by year
2026: 20 · 2025: 15
FWCI
25.70
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Blood Advances (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
Keywords
TP53 mutation, variant allele frequency, myelodysplastic syndrome, acute myeloid leukemia, hematopoietic stem cell transplantation, prognostic factors, cytogenetics, 5q deletion, 7q deletion, monosomy 7, matched related donor, progression-free survival, classification and regression trees
MeSH terms
Adult, Aged, Female, Gene Frequency, Humans, Male, Middle Aged, Mutation, Myelodysplastic Syndromes, Prognosis, Leukemia, Myeloid, Acute, Tumor Suppressor Protein p53, Hematopoietic Stem Cell Transplantation, Young Adult

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