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Flow cytometry-based measurable residual disease (MRD) analysis identifies AML patients who may benefit from allogeneic hematopoietic stem cell transplantation

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Abstract  

Measurable residual disease (MRD) monitoring independently predicts long-term outcomes in patients with acute myeloid leukemia (AML). Of the various modalities available, multiparameter flow cytometry–based MRD analysis is widely used and relevant for patients without molecular targets. In the transplant (HCT) setting, the presence of MRD pre-HCT is associated with adverse outcomes. MRD-negative remission status pre-HCT was also associated with longer overall (OS) and progression-free survival and a lower risk of relapse. We hypothesize that the combination of disease risk and MRD at the time of first complete remission (CR1) could identify patients according to the benefit gained from HCT, especially for intermediate-risk patients. We performed a retrospective analysis comparing the outcomes of HCT versus non-HCT therapies based on MRD status in AML patients who achieved CR1. Time-dependent analysis was applied considering time-to-HCT as a time-dependent covariate and compared HCT versus non-HCT outcomes according to MRD status at CR1. Among 336 patients assessed at CR1, 35.1% were MRD positive (MRDpos) post-induction. MRDpos patients benefitted from HCT with improved OS and relapse-free survival (RFS), while no benefit was observed in MRDneg patients. In adverse-risk patients, HCT improved OS (HR for OS 0.55; p = 0.05). In intermediate-risk patients, HCT benefit was not significant for OS and RFS. Intermediate-risk MRDpos patients were found to have benefit from HCT with improved OS (HR 0.45, p = 0.04), RFS (HR 0.46, p = 0.02), and CIR (HR 0.41, p = 0.02). Our data underscore the benefit of HCT in adverse risk and MRDpos intermediate-risk AML patients.

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Data availability

The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada

    Josephine Lucero, Igor Novitzky-Basso, Vikas Gupta, Aniket Bankar, Steven Chan, Andre C. Schuh, Mark Minden, Jonas Mattsson, Rajat Kumar, Hassan Sibai & Dennis D. H. Kim

  2. King Saud Medical City, Riyadh, Saudi Arabia

    Muhned Alhumaid

  3. Advanced Molecular Diagnostics Laboratory, Princess Margaret Cancer Centre, Toronto, ON, Canada

    Jose-Mario Capo-Chichi

  4. Division of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada

    Tracy Stockley

  5. Division of Hematology and Transfusion Medicine, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada

    Anne Tierens

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Contributions

JL and MA acquired data, interpreted results, drafted, and revised the manuscript. VG, ACS, and JM provided feedback on data analysis and the manuscript. INB revised the manuscript. JMC, TS, AB, SC, MM, RK, HS, and AT approved the final version. DDK acquired data, interpreted results, revised, and approved the final manuscript.

Corresponding authors

Correspondence to Josephine Lucero or Dennis D. H. Kim.

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Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Informed consent was not obtained due to the retrospective nature of the review of data. All personal health information has been de-identified.

Conflict of interest

JL, MA, INB, JMC, TS, AB, SC, ACS, MM, JM, RK, HS, AT, and DDK declare that they have no conflict of interest. VG reports consulting fees from AbbVie, Bristol Myers Squibb/Celgene, Constellation Biopharma, Novartis, Pfizer, and Sierra Oncology; honoraria from Bristol Myers Squibb/Celgene, Constellation Biopharma, and Novartis; and participation in the data safety monitoring board or advisory board for AbbVie, Bristol Myers Squibb/Celgene, Pfizer, and Roche.

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On behalf of the PMH MRD working group.

JL and MA contributed to the work equally as co-first authors.

HS, AT, and DDK contributed to the work equally as co-senior authors.

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Lucero, J., Alhumaid, M., Novitzky-Basso, I. et al. Flow cytometry-based measurable residual disease (MRD) analysis identifies AML patients who may benefit from allogeneic hematopoietic stem cell transplantation. Ann Hematol 103, 1187–1196 (2024). https://doi.org/10.1007/s00277-024-05639-6

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