Prognostic value of minimal residual disease measured by fusion-gene transcript in infants with KMT2A-rearranged acute lymphoblastic leukaemia treated according to the MLL-Baby protocol

Br J Haematol. 2021 Jun;193(6):1151-1156. doi: 10.1111/bjh.17304. Epub 2021 Feb 14.

Abstract

The prognostic value of minimal residual disease (MRD) measured by fusion-gene transcript (FGT) detection was investigated in 76 infants (aged ≤1 year) with acute lymphoblastic leukaemia (ALL) with lysine methyltransferase 2A (KMT2A) rearrangements. Either at the end of induction or at later time-points, FGT-MRD-positivity was associated with poor outcome. FGT-MRD-positivity after first consolidation or first high-risk block detected 46·5% of infants with extremely poor outcome [disease-free survival (SE) 0·06 (0·06), cumulative incidence of relapse (SE) 0·91 (0·05)], which was also confirmed in multivariable analysis. Thus, FGT-MRD measurement at a single time-point clearly identifies infants with ALL who are curable with conventional chemotherapy and those who would benefit only from other treatment approaches.

Keywords: KMT2A; acute lymphoblastic leukaemia; fusion-gene transcripts; infants; minimal residual disease.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Disease-Free Survival
  • Female
  • Histone-Lysine N-Methyltransferase* / blood
  • Histone-Lysine N-Methyltransferase* / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Myeloid-Lymphoid Leukemia Protein* / blood
  • Myeloid-Lymphoid Leukemia Protein* / genetics
  • Neoplasm, Residual
  • Oncogene Proteins, Fusion* / blood
  • Oncogene Proteins, Fusion* / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Survival Rate

Substances

  • KMT2A protein, human
  • Oncogene Proteins, Fusion
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase