title: Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome-negative acute lymphoblastic leukemia in the era of minimal residual disease.
abstract: The introduction of novel prognostic factors such as minimal residual disease (MRD) and genomic profiling has led to the reevaluation of the role of cytogenetics and other conventional factors in risk stratification for acute lymphoblastic leukemia (ALL).
  
  
  
  This study assessed the impact of baseline cytogenetics on the outcomes of 428 adult patients with Philadelphia chromosome-negative ALL who were receiving frontline chemotherapy. Three hundred thirty patients (77%) were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone-based regimens, and 98 (23%) were treated with the augmented Berlin-Frankfurt-Munster regimen.
  
  
  
  The median age was 40 years (range, 13-86 years). One hundred eighty-six patients (43%) had diploid cytogenetics, 32 (7%) had complex cytogenetics (defined as ≥ 5 chromosomal abnormalities), 27 (6%) had low hypodiploidy/near-triploidy (Ho-Tr), 24 (6%) had high hyperdiploidy, and 24 (6%) had a mixed-lineage leukemia (MLL) rearrangement. Patients with an MLL rearrangement, Ho-Tr, or a complex karyotype had significantly worse relapse-free survival (RFS) and overall survival (OS) than the diploid group. According to a multivariate analysis including all the baseline characteristics and MRD status, Ho-Tr and a complex karyotype were independent predictive factors for worse RFS and OS. Furthermore, survival among all cytogenetic groups was similar, regardless of the treatment received.
  
  
  
  A complex karyotype and Ho-Tr are adverse prognostic factors for adults with ALL independently of the MRD status. These findings suggest that pretreatment cytogenetics remain a valuable prognostic tool in this population. Cancer 2017;123:459-467. © 2016 American Cancer Society.
authors.affiliation: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ghayas C
authors.initials: GC
authors.lastname: Issa
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: C Cameron
authors.initials: CC
authors.lastname: Yin
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Wei
authors.initials: W
authors.lastname: Qiao
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Short
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Koji
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Tapan M
authors.initials: TM
authors.lastname: Kadia
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Naval
authors.initials: N
authors.lastname: Daver
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nitin
authors.initials: N
authors.lastname: Jain
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
authors.affiliation: Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Issa
authors.initials: I
authors.lastname: Khouri
authors.affiliation: Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.affiliation: Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.affiliation: Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, California.
authors.forename: Susan M
authors.identifier: 0000-0003-3386-6540
authors.initials: SM
authors.lastname: O'Brien
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003561:Cytarabine / Q000008:administration & dosage; D003581:Cytodiagnosis; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000235:genetics / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D012074:Remission Induction; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D014750:Vincristine; D004317:Doxorubicin
keywords: acute lymphoblastic leukemia (ALL); complex; cytogenetics; hypodiploidy; minimal residual disease; prognosis