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Impact of induction intensity and transplantation on outcomes of patients with complex karyotype and TP53-mutated acute myeloid leukemia

Bone Marrow Transplantation volume 58, pages 823–825 (2023)Cite this article

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Acute myeloid leukemia (AML) with both TP53 alterations and complex karyotype (CK) is associated with a poor response to conventional chemotherapy, high risk of relapse and short overall survival (OS). The presence of TP53 mutation is linked to refractoriness to intensive induction and the most effective induction regimen for this entity is unclear [1]. Many centers still use 7 days of cytarabine and 3 days of an anthracycline (7 + 3) as upfront therapy in patients fit to receive intensive chemotherapy. Venetoclax with hypomethylating agent (HMA/Ven), CPX-351 and various high-dose cytarabine containing regimens are also used as front-line therapy in this high-risk population, with variable results [2,3,4]. Furthermore, the role of consolidation with allogeneic stem cell transplantation (allo-SCT) is controversial in this population because of the very high risk of post-transplant relapse. However, as allo-SCT remains the only potentially curative treatment option for a subset of these patients, its role needs further investigation [5, 6]. Within this context, we conducted a retrospective analysis to investigate the impact of various induction regimens, along with consolidation with allo-SCT, on the outcomes of patients with CK and TP53-mutated AML, treated at our institution between January 2013 and May 2020. Institutional Review Board (IRB) approval was obtained.

We identified patients with TP53/CK (Both CK and TP53) AML through electronic medical records. Variables captured included age, gender, race, AML subtype (de novo, therapy-related, secondary), TP53 variant allelic frequency (VAF), TP53 single vs. double mutation, additional mutations, and treatment details. Outcomes of interest included composite complete remission (CR) rate (CR + CR with incomplete hematological recovery (CRi)) and OS. Measurable residual disease (MRD) was assessed using flow cytometry validated to a sensitivity level of 0.1%. Summary statistics, including the median and range for continuous variables and frequencies and percentages for categorical variables, were calculated. The OS rate was determined using Kaplan-Meier estimates. The χ2 test was used to compare the categorical values, and the Student t test was used to compare continuous variables. The log-rank test was used for univariate analysis, and the adjusted multiple logistic regression model was used for multivariate analysis. Variables with 2-tailed P < 0.05 on univariate analysis were selected for the multivariable models. Statistical analyses were performed using SAS, version 9.4 (SAS Institute, Inc, Cary, NC).

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Fig. 1: Survival outcomes.

Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Omer Jamy, Kendall Diebold, Kimo Bachiashvili, Sravanti Rangaraju, Pankit Vachhani, Kelly N. Godby, Donna Salzman & Ravi Bhatia

  2. School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Kenneth Davis

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Contributions

OJ contributed towards the conception of the presented study. OJ and KD contributed towards data collection and analysis. OJ, KD, KD, KB, SR, PV, KG, DS, and RB contributed towards drafting, revising, and approving the manuscript.

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Correspondence to Omer Jamy.

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Competing interests

PV has received consulting fees from AbbVie, Amgen, Blueprint Medicines, CTI biopharma, Genentech, Incyte, Novartis, and Pfizer. All other authors have no relevant conflict of interest to disclose.

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Jamy, O., Diebold, K., Davis, K. et al. Impact of induction intensity and transplantation on outcomes of patients with complex karyotype and TP53-mutated acute myeloid leukemia. Bone Marrow Transplant 58, 823–825 (2023). https://doi.org/10.1038/s41409-023-01977-7

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