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Significance of measurable residual disease in adults with secondary acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation volume 57, pages 1732–1734 (2022)Cite this article

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Many studies, including from our institution, have demonstrated an association between measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) and increased relapse risk/shorter survival in adults with acute myeloid leukemia (AML) [1,2,3]. While many of these studies have included patients with secondary AML, most have not focused on potential differences in the prognostic significance of MRD for patients with de novo AML relative to those with secondary disease. However, in a recent analysis from the Acute Leukemia Working Party of the European Society of Blood and Marrow Transplantation that encompassed 318 adults age 18–75 years with secondary AML, Maffini and colleagues reported no difference in post-HCT outcomes between patients with and without MRD at the time of allografting [4, 5]. An acknowledged limitation of such registry-based data is the heterogeneity in the MRD testing across the study cohort with lacking information regarding quality and performance characteristics of the MRD assays [4]. We therefore sought to determine the relative prognostic significance of MRD in adults with de novo or secondary AML who had pre-HCT MRD assessed uniformly.

To this end, we studied all adults ≥18 years with AML who underwent allografting while in first or second remission between 4/2006 and 5/2021 and had bone marrow MRD testing by multiparameter flow cytometry (MFC) before HCT [6]. The MRD assay was essentially unchanged throughout the study period, detecting MRD in most cases to a level of 0.1% and in progressively smaller subsets of patients as the level of MRD decreases below that level [7]. Following our previous approach, any detectable level of MRD was considered positive [6, 7]. The refined MRC/NCRI criteria [8] were used to assign cytogenetic risk at diagnosis. Secondary AML was defined as disease following an antecedent hematologic disorder or treatment with systemic chemotherapy and/or radiotherapy for a different disorder [6, 7]. Treatment response was categorized via 2017 European LeukemiaNet (ELN) criteria [9] except that relapse was defined as emergence of >5% blasts in blood or marrow, emergence of cytogenetic abnormalities seen previously, or presence/emergence of any level of disease if therapeutically intervened on [6, 7]. Data follow-up was current as of February 10, 2022.

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Fig. 1: Post-HCT outcomes for 257 adults with secondary AML and 722 adults with de novo AML undergoing allogeneic HCT, stratified by pre-HCT MRD status.

Data availability

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

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Acknowledgements

The authors acknowledge the excellent care provided by the physicians and nurses of the HCT teams, the staff in the Long-Term Follow-up office at the Fred Hutchinson Cancer Center, and the patients for participating in our research protocols.

Funding

Research reported in this publication was supported by grants P01-CA078902, P01-CA018029, and P30-CA015704 from the National Cancer Institute/National Institutes of Health (NCI/NIH), Bethesda, MD, USA.

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Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA

    Eduardo Rodríguez-Arbolí, Corentin Orvain & Roland B. Walter

  2. Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS/CSIC/CIBERONC), University of Seville, Seville, Spain

    Eduardo Rodríguez-Arbolí

  3. Public Health Science Division, Fred Hutchinson Cancer Center, Seattle, WA, USA

    Megan Othus

  4. Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA

    Roland B. Walter

  5. Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA

    Roland B. Walter

  6. Department of Epidemiology, University of Washington, Seattle, WA, USA

    Roland B. Walter

Authors
  1. Eduardo Rodríguez-Arbolí
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  2. Corentin Orvain
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  3. Megan Othus
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  4. Roland B. Walter
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Contributions

ERA and RBW conceptualized and designed this study and participated in data analysis and interpretation and drafting of the manuscript. CO and MO conducted statistical analyses and participated in data interpretation and drafting of the manuscript. All authors revised the manuscript critically and gave final approval to submit for publication.

Corresponding author

Correspondence to Roland B. Walter.

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The authors declare no competing interests.

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Rodríguez-Arbolí, E., Orvain, C., Othus, M. et al. Significance of measurable residual disease in adults with secondary acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 57, 1732–1734 (2022). https://doi.org/10.1038/s41409-022-01794-4

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