Measurable residual disease after the first consolidation predicts the outcomes of patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

Int J Hematol. 2020 Sep;112(3):349-360. doi: 10.1007/s12185-020-02911-z. Epub 2020 Jun 10.

Abstract

We stratified patients with newly diagnosed acute promyelocytic leukemia (APL) according to a white blood cell (WBC) count of ≥ 3 × 109/L (high risk) or < 3 × 109/L (low risk) before administering risk-adapted chemotherapy in combination with all-trans retinoic acid (ATRA). In total, 27 low-risk and 23 high-risk patients were assigned to receive induction and three courses of consolidation with ATRA and anthracycline, followed by 2-year maintenance regimen. High-risk group additionally received cytarabine during 1st consolidation and another one-shot idarubicin treatment during 3rd consolidation. We prospectively monitored measurable residual disease (MRD) after induction and each consolidation. In the low-risk and high-risk groups, 5-year disease-free survival (DFS) rates were 86.5% and 81.2% (p = 0.862), and 5-year overall survival rates were 100% and 84.8% (p = 0.062), respectively. In the MRD-negative and MRD-positive groups, 5-year DFS rates were 91.7% and 78.4% (p = 0.402) and 84.7% and 60.0% (p = 0.102) after induction and 1st consolidation, respectively. Relapse rates were 8.3% and 13.3% (p = 0.570) and 9.0% and 40.0% (p = 0.076) after induction and 1st consolidation, respectively. Achieving MRD-negativity after 1st consolidation, rather than after induction, was a potential predictor of relapse and DFS in patients with APL treated with ATRA + chemotherapy.

Keywords: APL; ATRA; MRD; PML–RARA; Stratification.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Consolidation Chemotherapy*
  • Cytarabine / administration & dosage
  • Female
  • Forecasting
  • Humans
  • Idarubicin / administration & dosage
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / mortality
  • Male
  • Middle Aged
  • Neoplasm, Residual / diagnosis
  • Neoplasm, Residual / mortality*
  • Prognosis
  • Prospective Studies
  • Recurrence
  • Survival Rate
  • Treatment Outcome
  • Tretinoin / administration & dosage
  • Tretinoin / therapeutic use*
  • Young Adult

Substances

  • Cytarabine
  • Tretinoin
  • Idarubicin