title: Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia.
abstract: Our aim was to improve outcome prediction after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia by combining cytogenetic and molecular data at diagnosis with minimal residual disease assessment by multicolor flow-cytometry at transplantation. Patients with acute myeloid leukemia in first complete remission in whom minimal residual disease was assessed at transplantation were included and categorized according to the European LeukemiaNet classification. The primary outcome was 1-year relapse incidence after transplantation. Of 152 patients eligible, 48 had minimal residual disease at the time of their transplant. Minimal residual disease-positive patients were older, required more therapy to achieve first remission, were more likely to have incomplete recovery of blood counts and had more adverse risk features by cytogenetics. Relapse incidence at 1 year was higher in patients with minimal residual disease (32.6% versus 14.4%, P=0.002). Leukemia-free survival (43.6% versus 64%, P=0.007) and overall survival (48.8% versus 66.9%, P=0.008) rates were also inferior in patients with minimal residual disease. In multivariable analysis, minimal residual disease status at transplantation independently predicted 1-year relapse incidence, identifying a subgroup of intermediate-risk patients, according to the European LeukemiaNet classification, with a particularly poor outcome. Assessment of minimal residual disease at transplantation in combination with cytogenetic and molecular findings provides powerful independent prognostic information in acute myeloid leukemia, lending support to the incorporation of minimal residual disease detection to refine risk stratification and develop a more individualized approach during hematopoietic stem cell transplantation.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA boran@mdanderson.org.
authors.forename: Betül
authors.initials: B
authors.lastname: Oran
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jeff L
authors.initials: JL
authors.lastname: Jorgensen
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: David
authors.initials: D
authors.lastname: Marin
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sa
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sairah
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Amin M
authors.initials: AM
authors.lastname: Alousi
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Borje S
authors.initials: BS
authors.lastname: Andersson
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Qaiser
authors.initials: Q
authors.lastname: Bashir
authors.affiliation: Department Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Bassett
authors.affiliation: Department Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Lyons
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Julianne
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Katy
authors.initials: K
authors.lastname: Rezvani
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Uday
authors.initials: U
authors.lastname: Popat
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.affiliation: Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D020732:Cytogenetic Analysis; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D018365:Neoplasm, Residual / Q000175:diagnosis*; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D019172:Transplantation Conditioning; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor