Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: A meta-analysis

Sarah A. Buckley, Brent L. Wood, Megan Othus, Christopher S. Hourigan, Celalettin Ustun, Michael A. Linden, Todd E. Defor, Michele Malagola, Chloe Anthias, Veronika Valkova, Christopher G. Kanakry, Bernd Gruhn, Francesco Buccisano, Beth Devine, Roland B. Walter

Research output: Contribution to journalReview articlepeer-review

120 Scopus citations


Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multipara-metric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (hazard ratio=2.76 [1.90-4.00]), overall survival (hazard ratio=2.36 [1.73-3.22]), and cumulative incidence of relapse (hazard ratio=3.65 [2.53-5.27]), but not non-relapse mortality (hazard ratio=1.12 [0.81-1.55]). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than WT1 polymerase chain reaction-based detection (I2=75.1% vs. <0.1% for leukemia-free survival, 67.8% vs. <0.1% for overall survival, and 22.1% vs. <0.1% for cumulative incidence of relapse). These results demonstrate a strong relationship between pre-transplant minimal residual disease and post-transplant relapse and survival. Outcome heterogeneity among studies using flow-based methods may underscore site-specific methodological differences or differences in test performance and interpretation.

Original languageEnglish (US)
Pages (from-to)865-873
Number of pages9
Issue number5
StatePublished - Apr 30 2017

Bibliographical note

Funding Information:
SAB is supported by a fellowship training grant from the National Heart, Lung, and Blood Institute/National Institutes of Health (NHLBI/NIH: T32-HL007093). R.B.W. is a Leukemia & Lymphoma Society Scholar in Clinical Research. This work was supported in part by the Intramural Research Programs of the National Heart, Lung, and Blood Institute and the National Cancer Institute of the National Institutes of Health.

Publisher Copyright:
© 2017 Ferrata Storti Foundation.


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