Prognostic significance of flow-cytometry evaluation of minimal residual disease in children with acute myeloid leukaemia treated according to the AIEOP-AML 2002/01 study protocol

Br J Haematol. 2017 Apr;177(1):116-126. doi: 10.1111/bjh.14523. Epub 2017 Feb 27.

Abstract

In children with acute myeloid leukaemia (AML), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. We report on the measurement of minimal residual disease (MRD), by multicolour flow-cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica-AML 2002/01 trial. At the end of the first induction course, MRD was <0·1% in 69, 0·1-1% in 16 and >1% in 51 patients. The 8-year disease-free survival (DFS) of 125 children in morphological complete remission and with MRD <0·1%, 0·1-1% and ≥1% was 73·1 ± 5·6%, 37·8 ± 12·1% and 34·1 ± 8·8%, respectively (P < 0·01). MRD was also available after the second induction course in 92/142 patients. MRD was ≥0·1% at the end of the first induction course in 36 patients; 13 reached an MRD <0·1% after the second one and their DFS was 45·4 ± 16·7% vs. 22·8 ± 8·9% in patients with persisting MRD ≥0·1% (P = 0·037). Multivariate analysis demonstrated that MRD ≥0·1% after first induction course was, together with a monosomal karyotype, an independent adverse prognostic factor for DFS. Our results show that MRD detected by flow-cytometry after induction therapy predicts outcome in patients with childhood AML and can help stratifying post-remission treatment.

Keywords: Acute myeloid leukaemia; Flow-cytometry; Minimal residual disease; Paediatric; Risk group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Immunophenotyping
  • Infant
  • Infant, Newborn
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / mortality*
  • Male
  • Multivariate Analysis
  • Neoplasm, Residual / diagnosis*
  • Prognosis
  • Survival Analysis
  • Treatment Outcome