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Acute myeloid leukemia

Impact of pretransplant measurable residual disease on the outcome of allogeneic hematopoietic cell transplantation in adult monosomal karyotype AML

Leukemia volume 34, pages 1577–1587 (2020)Cite this article

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Abstract

Allogeneic hematopoietic cell transplantation (HCT) is often unsuccessful for monosomal karyotype (MK) acute myeloid leukemia (AML). To what degree failures are associated with pretransplant measurable residual disease (MRD)—a dominant adverse-risk factor—is unknown. We therefore studied 606 adults with intermediate- or adverse-risk AML in morphologic remission who underwent allogeneic HCT between 4/2006 and 1/2019. Sixty-eight (11%) patients had MK AML, the majority of whom with complex cytogenetics. Before HCT, MK AML patients more often tested MRDpos by multiparameter flow cytometry (49 vs. 18%; P < 0.001) and more likely had persistent cytogenetic abnormalities (44 vs. 13%; P < 0.001) than non-MK AML patients. Three-year relapse/overall survival estimates were 46%/43% and 72%/15% for MRDneg and MRDpos MK AML patients, respectively, contrasted to 20%/64% and 64%/38% for MRDneg and MRDpos non-MK AML patients, respectively. After multivariable adjustment, MRDpos remission status but not MK remained statistically significantly associated with shorter survival and higher relapse risk. Similar results were obtained in several patient subsets. In summary, while our study confirms higher relapse rates and shorter survival for MK-AML compared with non-MK AML patients, these outcomes are largely accounted for by the presence of other adverse prognostic factors, in particular higher likelihood of pre-HCT MRD.

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Fig. 1: Association between pretransplant MRD status and posttransplant outcome for 68 adults with MK AML and 538 adults with non-MK AML undergoing allogeneic HCT while in first or second morphologic remission.
Fig. 2: Posttransplant outcomes for distinct subsets of patients with MK AML and non-MK AML, stratified by pretransplant MRD status.

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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 Research Center, the Hematopathology Laboratory at the University of Washington, and the patients for participating in our research protocols. This work was supported by grants P01-CA078902, P01-CA018029, and P30-CA015704 from the National Cancer Institute/National Institutes of Health (NCI/NIH).

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Author notes

  1. Linde M. Morsink

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

  2. Evandro D. Bezerra

    Present address: Division of Hematology, Mayo Clinic, Rochester, MN, USA

Authors and Affiliations

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

    Linde M. Morsink, Min Fang, Brenda M. Sandmaier, Marco Mielcarek, Gary Schoch, Rainer Storb, H. Joachim Deeg, Frederick R. Appelbaum & Roland B. Walter

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

    Megan Othus

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

    Evandro D. Bezerra

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

    Brent L. Wood

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

    Min Fang & Roland B. Walter

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

    Brenda M. Sandmaier, Marco Mielcarek, Rainer Storb, H. Joachim Deeg & Frederick R. Appelbaum

  7. Division of Hematology, Department of Medicine, 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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Morsink, L.M., Othus, M., Bezerra, E.D. et al. Impact of pretransplant measurable residual disease on the outcome of allogeneic hematopoietic cell transplantation in adult monosomal karyotype AML. Leukemia 34, 1577–1587 (2020). https://doi.org/10.1038/s41375-020-0717-0

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