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Barriers to allogeneic stem cell transplantation in responding patients with TP53-mutated acute myeloid leukemia

Bone Marrow Transplantation volume 60, pages 910–913 (2025)Cite this article

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Despite the improvement in overall outcomes of patients with acute myeloid leukemia (AML), some high-risk disease subsets continue to fare dismally. AML with TP53 aberrations (mutations, deletions) is one such subset of high-risk AML with a median survival of about 6–9 months [1,2,3]. Long-term survival of these patients is highly contingent upon a successful allogeneic hematopoietic stem cell transplantation (HSCT) as consolidation after the achievement of at least a morphological remission, but preferably a measurable residual disease (MRD) negative remission [4]. While venetoclax-based therapies have not led to improvement in survival in AML with TP53 aberrations, response rates (composite complete response [CRc] and overall/objective response [OR]) are higher with venetoclax-based therapy [5, 6]. However, a significant proportion of patients with TP53 mutated AML are unable to undergo an HSCT despite achieving a response, being young, and having a potential donor [7]. In a recent retrospective analysis of TP53 mutated AML from MD Anderson (291 patients, treated during 2013–2021), only 20% patients could be transplanted with a median OS of 14 months in transplanted patients compared to 9.4 months in the non -transplanted landmarked comparator arm of responding patients [1]. In another large multicenter analysis, HSCT was the only factor associated with improved survival in TP53 mutated AML on multivariate analysis (Hazard ratio 0.25, 95% CI 0.15–0.42) [8]. While short duration of responses (DORs) remains an important barrier to HSCT consolidation, often patients with TP53 mutated AML have poor performance status (PS), infections, or other comorbidities precluding an HSCT. In the present analysis, we evaluate a large cohort of patients with newly-diagnosed TP53 mutated AML and interrogate outcomes with HSCT and barriers to HSCT.

We retrospectively reviewed patients with newly-diagnosed AML treated at MD Anderson Cancer Center from Jan 2017-Jan 2024 and included all patients with TP53 mutation(s) and selected patients who had achieved at least an overall response (OR) with frontline therapy. TP53 mutation(s) were identified in diagnostic bone marrow (BM) with next-generation sequencing (NGS) using our clinically validated myeloid panels, interrogating the entire exonic or hotspot regions of 81 genes (including TP53) frequently mutated in myeloid malignancies, with a lower limit of detection of ≥2% variant allelic frequency (VAF) [9]. Baseline characteristics including age, cytogenetics, treatment intensity, use of venetoclax, response and MRD status were captured from electronic health records. MRD was assessed using multiparameter flow cytometry at a level of sensitivity up to 10−4 [10]. Response was captured as CRc (complete remission [CR] or CR with incomplete counts recovery [CRi]) while OR included CRc + morphological leukemia free state (MLFS). Relapse free survival (RFS) was defined as time from best response to relapse or death, and overall survival (OS) from treatment initiation to death, and both were censored at last follow up. At our institution all patients up to 75 years of age with high-risk AML are eligible for referral for HSCT. Individual chart review was done to understand barriers to HSCT in responding patients of this age group.

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Fig. 1: Proprtion of patients with TP53 mutated AML who could be transplanted and barriers to HSCT.

Data availability

Data available from corresponding author on reasonable request.

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Funding

The study was supported by University of Texas MD Anderson Cancer Center Grant (CA016672) and University of Texas MD Anderson SPORE (C1100632).

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Authors and Affiliations

  1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jayastu Senapati, Guillermo Garcia-Manero, Courtney D. DiNardo, Indraneel Deshmukh, Gautam Borthakur, Tapan M. Kadia, Elias Jabbour, Nicholas J. Short, Hussein A. Abbas, Naveen Pemmaraju, Nitin Jain, Fadi G. Haddad, Ghayas C. Issa, Abhishek Maiti, Musa Yilmaz, Yesid Alvarado, Guillermo Montalban-Bravo, Farhad Ravandi, Hagop M. Kantarjian & Naval G. Daver

  2. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Elizabeth Shpall & Uday Popat

  3. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Sanam Loghavi & Guilin Tang

Authors
  1. Jayastu Senapati
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  2. Guillermo Garcia-Manero
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  18. Guilin Tang
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  23. Hagop M. Kantarjian
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  24. Naval G. Daver
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Contributions

JS and NGD designed the study. JS and ID collected the data. JS analyzed the data and wrote the first draft. JS, GGM, CDD, GB, TMK, EJ, NJS, HAA, NP, NJ, FGH, GCI, AM, ES, UP, SL, GT, MY, YA, GMB, FR, HMK and NGD provided patients. All authors reviewed the final draft and approved the manuscript.

Corresponding authors

Correspondence to Jayastu Senapati or Naval G. Daver.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Informed consent to participate in outcomes research retrospective studies was procured for all patients on this study. The study was approved by the Institutional review board umbrella protocol for retrospective studies (PA11-0788) and the study was conducted as per the Declaration of Helsinki and other relevant guidelines and regulations.

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Senapati, J., Garcia-Manero, G., DiNardo, C.D. et al. Barriers to allogeneic stem cell transplantation in responding patients with TP53-mutated acute myeloid leukemia. Bone Marrow Transplant 60, 910–913 (2025). https://doi.org/10.1038/s41409-025-02590-6

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