Prognostic significance of day 14 bone marrow evaluation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia

Cancer. 2016 Dec 15;122(24):3812-3820. doi: 10.1002/cncr.30262. Epub 2016 Aug 10.

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.

Keywords: acute lymphoblastic leukemia; blasts; day 14; minimal residual disease; prognosis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow / pathology*
  • Bone Marrow Examination / methods
  • Disease-Free Survival
  • Female
  • Humans
  • Induction Chemotherapy / methods
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm, Residual / genetics
  • Neoplasm, Residual / pathology
  • Philadelphia Chromosome
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Prognosis
  • Proportional Hazards Models
  • Remission Induction / methods
  • Young Adult