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Acute myeloid leukemia

Pre- and post-transplant quantification of measurable (‘minimal’) residual disease via multiparameter flow cytometry in adult acute myeloid leukemia

Leukemia volume 30, pages 1456–1464 (2016)Cite this article

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Abstract

Measurable (‘minimal’) residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRDneg/MRDneg patients had excellent outcomes, whereas both MRDneg/MRDpos patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRDpos patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies.

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Acknowledgements

Research reported in this publication was supported by a grant from the National Cancer Institute/National Institutes of Health (NCI/NIH: P30-CA015704) and a fellowship training grant from the National Heart, Lung, and Blood Institute/NIH (T32-HL007093; to ABH). RBW is a Leukemia & Lymphoma Society Scholar in Clinical Research. The authors thank the physicians and nurses of the HCT teams, the staff in the Long Term Follow-Up Program at the Fred Hutchinson Cancer Research Center, the Hematopathology Laboratory at the University of Washington, and our patients for assisting with our research protocols.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Division of Hematopathology, University of Washington, Seattle, WA, USA

    Y Zhou & B L Wood

  2. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    M Othus

  3. Department of Medicine, Residency Program, University of Washington, Seattle, WA, USA

    D Araki

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

    J P Radich, M Mielcarek, E H Estey, F R Appelbaum & R B Walter

  5. Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA

    J P Radich & M Mielcarek

  6. Hematology/Oncology Fellowship Program, University of Washington, Seattle, WA

    A B Halpern & F R Appelbaum

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

    E H Estey & R B Walter

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

    R B Walter

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  1. Y Zhou
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Correspondence to R B Walter.

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Zhou, Y., Othus, M., Araki, D. et al. Pre- and post-transplant quantification of measurable (‘minimal’) residual disease via multiparameter flow cytometry in adult acute myeloid leukemia. Leukemia 30, 1456–1464 (2016). https://doi.org/10.1038/leu.2016.46

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