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Cited by 78Acute Myeloid Leukemia ResearchHematopoietic Stem Cell TransplantationRetinoids in leukemia and cellular processes

Allogeneic Hematopoietic Cell Transplantation Improves Outcome in Myelodysplastic Syndrome Across High-Risk Genetic Subgroups: Genetic Analysis of the Blood and Marrow Transplant Clinical Trials Network 1102 Study

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Versluis, Jurjen, Saber, Wael, Tsai, Harrison K., Gibson, Christopher J., Dillon, Laura W., Mishra, Asmita, McGuirk, Joseph, Maziarz, Richard T. +11 more·2023·Journal of Clinical Oncology
DOI 10.1200/jco.23.00866PMC PMC10552956
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Abstract

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndrome (MDS) improves overall survival (OS). We evaluated the impact of MDS genetics on the benefit of HCT in a biological assignment (donor v no donor) study. METHODS: We performed targeted sequencing in 309 patients age 50-75 years with International Prognostic Scoring System (IPSS) intermediate-2 or high-risk MDS, enrolled in the Blood and Marrow Transplant Clinical Trials Network 1102 study and assessed the association of gene mutations with OS. Patients with TP53 mutations were classified as TP53 multihit if two alleles were altered (via point mutation, deletion, or copy-neutral loss of heterozygosity). RESULTS: The distribution of gene mutations was similar in the donor and no donor arms, with TP53 (28% v 29%; P = .89), ASXL1 (23% v 29%; P = .37), and SRSF2 (16% v 16%; P = .99) being most common. OS in patients with a TP53 mutation was worse compared with patients without TP53 mutation (21% ± 5% [SE] v 52% ± 4% at 3 years; P < .001). Among those with a TP53 mutation, OS was similar between TP53 single versus TP53 multihit (22% ± 8% v 20% ± 6% at 3 years; P = .31). Considering HCT as a time-dependent covariate, patients with a TP53 mutation who underwent HCT had improved OS compared with non-HCT treatment (OS at 3 years: 23% ± 7% v 11% ± 7%; P = .04), associated with a hazard ratio of 3.89; 95% CI, 1.87 to 8.12; P < .001 after adjustment for covariates. OS among patients with molecular IPSS (IPSS-M) very high risk without a TP53 mutation was significantly improved if they had a donor (68% ± 10% v 0% ± 12% at 3 years; P = .001). CONCLUSION: HCT improved OS compared with non-HCT treatment in patients with TP53 mutations irrespective of TP53 allelic status. Patients with IPSS-M very high risk without a TP53 mutation had favorable outcomes when a donor was available.

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Crossref · 10.1200/jco.23.00866

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  • In the BMT CTN 1102 study, there were no predictor factors for long-term survival (e.g., no difference in single vs. multihit mTP53).

    “although without predictor factors for patients with long‐term survival (e.g., no difference in single vs. multihit mTP53).”

    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 [44]

    The Results section, “Genetic Determinants of Outcomes,” reports similar three-year overall survival for patients with single-hit and multihit TP53 mutations, supporting the example. But the same section identifies TP53 and other mutations as associated with survival, so the broader claim that there were no predictive factors is overstated. Page numbers were not supplied in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In the BMT CTN 1102 study, mTP53 MDS patients had a 3-year OS of around 20% with transplant versus 7% without transplant.

    “prospective evaluation of mTP53 MDS patients from the BMT CTN 1102 study showed a 3‐year OS of around 20% (vs. 7% without transplant)”

    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 [44]

    The Results section reports three-year overall survival of 23% ± 7% for patients with TP53-mutated MDS who received transplant, supporting 'around 20%.' The paper reports 11% ± 7%, not 7%, for the non-transplant comparison; 7% is the reported standard error. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Historically, 2-year OS for this population is around 20%.

    “which historically is around 20%.”

    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 [44]

    The Results section (Genetic Determinants of Outcomes; page unavailable) reports approximately 20% overall survival for patients with TP53-mutated MDS, but at three years, not two. It reports an outcome in the study cohort rather than a historical two-year survival estimate. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Authors
Versluis, J., Saber, W., Tsai, H. K., Gibson, C. J., Dillon, L. W., Mishra, A., McGuirk, J., Maziarz, R. T., Westervelt, P., Hegde, P., Mukherjee, D., Martens, M. J., Logan, B., Horowitz, M., Hourigan, C. S., Nakamura, R., Cutler, C., Lindsley, R. C., & on behalf of the Blood and Marrow Transplant Clinical Trials Network
Affiliations
  • Harvard University (US)
  • Medical College of Wisconsin (US)
  • National Institutes of Health (US)
  • Moffitt Cancer Center (US)
  • The University of Kansas Cancer Center (US)
  • Oregon Health & Science University (US)
  • Washington University in St. Louis (US)
  • City Of Hope National Medical Center (US)
Corresponding author
Lindsley, R. Coleman
ORCID
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2023-10-01
Volume
41
Issue
28
Pages
4497-4510
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.23.00866
PMC
PMC10552956
OpenAlex
W4386054608
Cited by
78
References
34
Citations by year
2026: 19 · 2025: 35 · 2024: 19 · 2023: 4
FWCI
15.91
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of Clinical Oncology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by-nc-nd)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
Funders
  • National Heart, Lung, and Blood Institute (U01HL069294, UG1HL109137, UG1HL069278, U24HL138660)
  • National Cancer Institute (P01CA229092, U24CA076518)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
Keywords
myelodysplastic syndrome, allogeneic hematopoietic stem cell transplantation, TP53 mutation, ASXL1, SRSF2, overall survival, high-risk MDS, targeted sequencing, copy-neutral loss of heterozygosity
MeSH terms
Aged, Bone Marrow, Humans, Middle Aged, Mutation, Myelodysplastic Syndromes, Prognosis, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation

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