title: Pre- and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia.
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 MRD(neg)/MRD(neg) patients had excellent outcomes, whereas both MRD(neg)/MRD(pos) 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 MRD(pos) 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.
authors.affiliation: Department of Laboratory Medicine, Division of Hematopathology, University of Washington, Seattle, WA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Othus
authors.affiliation: Department of Medicine, Residency Program, University of Washington, Seattle, WA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Araki
authors.affiliation: Department of Laboratory Medicine, Division of Hematopathology, University of Washington, Seattle, WA, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Wood
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Radich
authors.affiliation: Hematology/Oncology Fellowship Program, University of Washington, Seattle, WA.
authors.forename: A B
authors.initials: AB
authors.lastname: Halpern
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mielcarek
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Estey
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Hematology/Oncology Fellowship Program, University of Washington, Seattle, WA.
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA.|Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Walter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001856:Bone Marrow Examination; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000401:mortality; D011184:Postoperative Period; D057234:Preoperative Period; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D055815:Young Adult