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Early achievement of measurable residual disease (MRD)-negative complete remission as predictor of outcome after myeloablative allogeneic hematopoietic cell transplantation in acute myeloid leukemia

Bone Marrow Transplantation volume 55, pages 669–672 (2020)Cite this article

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Myeloablative allogeneic hematopoietic cell transplantation (HCT) is commonly used for acute myeloid leukemia (AML) in first morphologic remission [1]. Pre-HCT measurable (“minimal”) residual disease (MRD) is a major, independent indicator of relapse in this situation [2]. However, not all MRDpos patients relapse, and not all MRDneg patients are cured. Thus, there is interest in additional predictors to inform more accurately on expected outcomes and, possibly, develop risk-stratified therapies. We previously reported the number of induction courses required to enter remission adds prognostic information for post-HCT outcome independent of that provided by pre-HCT MRD testing [3]. Here, we examined whether achievement of an MRDneg complete remission (CR) after one course of chemotherapy (“early MRDneg CR”) is associated with better post-HCT outcomes than seen in patients who do not achieve this response (“no early MRDneg CR”).

We studied adults ≥ 18 years who received a first myeloablative allogeneic HCT with peripheral blood or bone marrow as a stem cell source while in first MRDneg CR or CR with incomplete hematologic recovery (CRi) and were evaluated for MRD by multiparameter flow cytometry (MFC) performed on bone marrow specimens obtained after the first cycle of induction chemotherapy and before HCT. We included patients regardless of how many cycles of chemotherapy were necessary to obtain morphologic remission and regardless of whether or not postremission chemotherapy was administered before allografting. Any measurable level of MRD was considered positive [4,5,6,7,8]; MRD test results were available to treating physicians. All patients were treated on institutional review board (IRB)-approved protocols or standard treatment protocols. Our retrospective analysis was approved by the Fred Hutchinson Cancer Research Center IRB. Follow-up was current as of April 29, 2019.

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Acknowledgements

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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Author notes

  1. Linde M. Morsink

    Present address: Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands

Authors and Affiliations

  1. Medical School, University of Washington, Seattle, WA, USA

    Alexander P. Hoffmann & Ashley L. Besch

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

    Megan Othus

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

    Linde M. Morsink, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum & Roland B. Walter

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

    Brent L. Wood

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

    Marco Mielcarek & Frederick R. Appelbaum

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

    Elihu H. Estey & Roland B. Walter

  7. Department of Pathology, University of Washington, Seattle, WA, USA

    Roland B. Walter

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

    Roland B. Walter

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  1. Alexander P. Hoffmann
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Contributions

APH collected and analyzed/interpreted data and drafted the manuscript. ALB and LMM collected data and revised the manuscript. MO analyzed/interpreted data, performed statistical analyses, and revised the manuscript. BLW, MM, EHE, and FRA contributed to the provision of study material and patient recruitment, analyzed/interpreted data, and revised the manuscript. RBW designed the study, collected and analyzed/interpreted data, performed statistical analyses, and drafted the manuscript.

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Correspondence to Roland B. Walter.

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Hoffmann, A.P., Besch, A.L., Othus, M. et al. Early achievement of measurable residual disease (MRD)-negative complete remission as predictor of outcome after myeloablative allogeneic hematopoietic cell transplantation in acute myeloid leukemia. Bone Marrow Transplant 55, 669–672 (2020). https://doi.org/10.1038/s41409-019-0739-2

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  • DOI: https://doi.org/10.1038/s41409-019-0739-2

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