Prognostic stratification of molecularly and clinically distinct subgroup in children with acute monocytic leukemia

Cancer Med. 2020 Jun;9(11):3647-3655. doi: 10.1002/cam4.3023. Epub 2020 Mar 26.

Abstract

Background: The prognosis of children with acute monocytic leukemia (AML-M5) remains unsatisfactory and the risk profile is still controversial. We aim to investigate the prognostic value of clinical and cytogenetic features and propose a new risk stratification in AML-M5 children.

Methods: We included 132 children with AML-M5. Overall survival (OS) and progression-free survival (PFS) were documented. Cox regression was performed to evaluate the potential risk factors of prognosis.

Results: The 5-year-OS was 46.0% (95% confidence intervals, 41.6%-50.4%) in all patients. There was significantly lower OS in the age ≤ 3 years old (P = .009) and hyperleukocytosis (P < .001). The FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) and MLL-rearrangement carriers were associated with fewer survivors in all patients (37.1% and 36.7%) and chemotherapy-only group (19.0% and 35.0%). Notably, the number of survivor with MLL-rearrangement did not increase in hematopoietic stem cell transplant (HSCT) group. According to the Cox regression analysis, HSCT was a significantly favorable factor (P = .001), while hyperleukocytosis, age ≤ 3 years old, and BM blast ≥ 70% adversely affected the OS in all patients (all P < .05). Additionally, FLT3-ITD was a risk factor for OS in the chemotherapy-only group (P = .023), while hyperleukocytosis and age ≤ 3 years independently contributed to poor PFS (both P < .05). In comparison to the standard-risk group, significant poorer outcome was found in the high-risk group (both P < .005).

Conclusions: We propose that AML-M5 children with any of MLL-rearrangement, FLT3-ITD, hyperleukocytosis, BM blast ≥ 70%, or age ≤ 3 years old are classified into the high-risk group, and HSCT is beneficial especially in patients with FLT3-ITD mutation, hyperleukocytosis, and age ≤ 3 years old. Importantly, the choice of HSCT should be made more carefully in children with MLL-rearrangement for its suboptimal performance.

Keywords: acute monocytic leukemia; children; clinical characteristics; gene mutation; prognostic factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Infant
  • Leukemia, Monocytic, Acute / classification
  • Leukemia, Monocytic, Acute / genetics
  • Leukemia, Monocytic, Acute / pathology*
  • Leukemia, Monocytic, Acute / therapy
  • Male
  • Mutation*
  • Prognosis
  • Survival Rate

Substances

  • Biomarkers, Tumor