title: Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission.
abstract: Minimal residual disease (MRD) before myeloablative hematopoietic cell transplantation (HCT) is associated with adverse outcome in acute myeloid leukemia (AML) in first complete remission (CR1). To compare this association with that for patients in second complete remission (CR2) and to examine the quantitative impact of MRD, we studied 253 consecutive patients receiving myeloablative HCT for AML in CR1 (n = 183) or CR2 (n = 70) who had pre-HCT marrow aspirates analyzed by 10-color flow cytometry. Three-year estimates of overall survival were 73% (64%-79%) and 32% (17%-48%) for MRDneg and MRDpos CR1 patients, respectively, and 73% (57%-83%) and 44% (21%-65%) for MRDneg and MRDpos CR2 patients, respectively. Similar estimates of relapse were 21% (14%-28%) and 58% (41%-72%) for MRDneg and MRDpos CR1 patients, respectively, and 19% (9%-31%) and 68% (41%-85%) for MRDneg and MRDpos CR2 patients, respectively. Among the MRDpos patients, there was no statistically significant evidence that increasing levels of MRD were associated with increasing risks of relapse and death. After multivariable adjustment, risks of death and relapse were 2.61 times and 4.90 times higher for MRD(pos) patients (P < .001). Together, our findings indicate that the negative impact of pre-HCT MRD is similar for AML in CR1 and CR2 with even minute levels (≤ 0.1%) as being associated with adverse outcome.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1924, USA. rwalter@fhcrc.org
authors.forename: Roland B
authors.initials: RB
authors.lastname: Walter
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Buckley
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.forename: Brent L
authors.initials: BL
authors.lastname: Wood
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.forename: Boglarka
authors.initials: B
authors.lastname: Gyurkocza
authors.forename: Colleen
authors.initials: C
authors.lastname: Delaney
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Elihu H
authors.initials: EH
authors.lastname: Estey
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003710:Demography; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018365:Neoplasm, Residual / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D012074:Remission Induction; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult