title: Prognostic significance of day 14 bone marrow evaluation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia.
abstract: BACKGROUND
  The role of day 14 (D14) bone marrow (BM) assessment in detecting increased blasts in patients undergoing induction for acute lymphoblastic leukemia (ALL) is not well defined.
  
  
  METHODS
  This study evaluated 389 adolescent and adult patients with previously untreated Philadelphia chromosome-negative ALL who received frontline induction chemotherapy and for whom a D14 BM assessment was performed.
  
  
  RESULTS
  A D14 BM blast proportion < 10% (including blast-free aplastic BM) was observed in 319 patients (82%), 10% to 29% was observed in 31 patients (8%), and ≥30% was observed in 39 patients (10%). The composite complete remission (CR)/complete remission with inadequate platelet recovery (CRp) rates for these groups were 99.7%, 87%, and 79%, respectively. The median event-free survival (EFS) was 49, 33, and 9 months, respectively (P < .001). The median overall survival (OS) was 88, 37, and 21 months, respectively (P < .001). The D14 BM blast group was the only factor predictive for the achievement of CR/CRp (P < .001). According to a multivariate analysis, the D14 BM blast group was independently prognostic for both EFS (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.12-1.85; P = .004) and OS (HR, 1.45; 95% CI, 1.14-1.85; P = .003). However, when minimal residual disease (MRD) assessment at the time of CR was added to the model, the D14 BM blast group was no longer prognostic for EFS or OS.
  
  
  CONCLUSIONS
  An assessment of residual D14 BM blasts in patients with ALL is highly predictive of the achievement of CR with induction chemotherapy and of EFS and OS. However, the D14 BM blast assessment is less prognostic of long-term outcomes when an MRD assessment is also available. Cancer 2016;122:3812-3820. © 2016 American Cancer Society.
authors: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Nicholas J
authors: NJ
authors: Short
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Hagop M
authors: HM
authors: Kantarjian
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Koji
authors: K
authors: Sasaki
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Jorge E
authors: JE
authors: Cortes
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Farhad
authors: F
authors: Ravandi
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Deborah A
authors: DA
authors: Thomas
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Guillermo
authors: G
authors: Garcia-Manero
authors: Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Issa
authors: I
authors: Khouri
authors: Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Partow
authors: P
authors: Kebriaei
authors: Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Richard E
authors: RE
authors: Champlin
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Sherry
authors: S
authors: Pierce
authors: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Ghayas C
authors: GC
authors: Issa
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Marina
authors: M
authors: Konopleva
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Tapan M
authors: TM
authors: Kadia
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Carlos
authors: C
authors: Bueso-Ramos
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Joseph D
authors: JD
authors: Khoury
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Nitin
authors: N
authors: Jain
authors: Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, California.
authors: Susan M
authors: http://orcid.org/0000-0003-3386-6540
authors: SM
authors: O'Brien
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Elias
authors: E
authors: Jabbour
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology*; D001856:Bone Marrow Examination / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018365:Neoplasm, Residual / Q000235:genetics / Q000473:pathology; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D012074:Remission Induction / Q000379:methods; D055815:Young Adult
keywords: acute lymphoblastic leukemia; blasts; day 14; minimal residual disease; prognosis