title: Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease-Based Definition of Complete Remission?
abstract: OBJECTIVE
  Patients with acute myeloid leukemia (AML) who are in morphologic complete remission are typically considered separately from patients with active disease (ie, ≥ 5% marrow blasts by morphology) in treatment algorithms for allogeneic hematopoietic cell transplantation (HCT), which implies distinct outcomes for these two groups. It is well recognized that the presence of minimal residual disease (MRD) at the time of transplantation is associated with adverse post-HCT outcome for those patients in morphologic remission. This effect of pre-HCT MRD prompted us to compare outcomes in consecutive patients in MRD-positive remission with patients with active AML who underwent myeloablative allogeneic HCT at our institution.
  
  
  METHODS
  We retrospectively studied 359 consecutive adults with AML who underwent myeloablative allogeneic HCT from a peripheral blood or bone marrow donor between 2006 and 2014. Pre-HCT disease staging included 10-color multiparametric flow cytometry on bone marrow aspirates in all patients. Any level of residual disease was considered to be MRD positive.
  
  
  RESULTS
  Three-year relapse estimates were 67% in 76 patients in MRD-positive morphologic remission and 65% in 48 patients with active AML compared with 22% in 235 patients in MRD-negative remission. Three-year overall survival estimates were 26%, 23%, and 73% in these three groups, respectively. After multivariable adjustment, MRD-negative remission status remained statistically significantly associated with longer overall and progression-free survival as well as lower risk of relapse compared with MRD-positive morphologic remission status or having active disease, with similar outcomes between the latter two groups.
  
  
  CONCLUSIONS
  The similarities in outcomes between patients in MRD-positive morphologic remission and those with active disease at the time of HCT support the use of treatment algorithms that use MRD- rather than morphology-based disease assessments.
authors.affiliation: Daisuke Araki, Brent L. Wood, Jerald P. Radich, Anna B. Halpern, Yi Zhou, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, University of Washington; and Megan Othus, Jerald P. Radich, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Araki
authors.affiliation: Daisuke Araki, Brent L. Wood, Jerald P. Radich, Anna B. Halpern, Yi Zhou, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, University of Washington; and Megan Othus, Jerald P. Radich, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Brent L
authors.initials: BL
authors.lastname: Wood
authors.affiliation: Daisuke Araki, Brent L. Wood, Jerald P. Radich, Anna B. Halpern, Yi Zhou, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, University of Washington; and Megan Othus, Jerald P. Radich, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Megan
authors.initials: M
authors.lastname: Othus
authors.affiliation: Daisuke Araki, Brent L. Wood, Jerald P. Radich, Anna B. Halpern, Yi Zhou, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, University of Washington; and Megan Othus, Jerald P. Radich, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.affiliation: Daisuke Araki, Brent L. Wood, Jerald P. Radich, Anna B. Halpern, Yi Zhou, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, University of Washington; and Megan Othus, Jerald P. Radich, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Anna B
authors.initials: AB
authors.lastname: Halpern
authors.affiliation: Daisuke Araki, Brent L. Wood, Jerald P. Radich, Anna B. Halpern, Yi Zhou, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, University of Washington; and Megan Othus, Jerald P. Radich, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Daisuke Araki, Brent L. Wood, Jerald P. Radich, Anna B. Halpern, Yi Zhou, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, University of Washington; and Megan Othus, Jerald P. Radich, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Marco
authors.initials: M
authors.lastname: Mielcarek
authors.affiliation: Daisuke Araki, Brent L. Wood, Jerald P. Radich, Anna B. Halpern, Yi Zhou, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, University of Washington; and Megan Othus, Jerald P. Radich, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Elihu H
authors.initials: EH
authors.lastname: Estey
authors.affiliation: Daisuke Araki, Brent L. Wood, Jerald P. Radich, Anna B. Halpern, Yi Zhou, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, University of Washington; and Megan Othus, Jerald P. Radich, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.affiliation: Daisuke Araki, Brent L. Wood, Jerald P. Radich, Anna B. Halpern, Yi Zhou, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, University of Washington; and Megan Othus, Jerald P. Radich, Marco Mielcarek, Elihu H. Estey, Frederick R. Appelbaum, and Roland B. Walter, Fred Hutchinson Cancer Research Center, Seattle, WA. rwalter@fredhutch.org.
authors.forename: Roland B
authors.initials: RB
authors.lastname: Walter
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D012074:Remission Induction; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult