Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations

Br J Haematol. 2010 Apr;149(1):84-92. doi: 10.1111/j.1365-2141.2009.08058.x. Epub 2010 Jan 18.

Abstract

Acute leukaemias of ambiguous lineage (ALAL) represent a rare type of leukaemia, expressing both myeloid and lymphoid markers. This study retrospectively analyzed data from 92 children (biphenotypic n = 78, bilineal n = 6, lineage switch n = 8) with ALAL registered in the Berlin-Frankfürt-Münster (BFM) acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) studies between 1998 and 2006 (2.4% of all cases with acute leukaemia). Our cohort of ALAL patients was characterized by comparatively high median age (8.9 years), high median white blood cell count (14.9 x 10(9)/l), as well as frequent hyperleucocytosis (18.5%) and central nervous system involvement (24.1%). The most frequent cytogenetic abnormalities were ETV6/RUNX1 fusion (16%) and trisomy 8 (14.6%). Complete remission rate was significantly lower than in ALL-BFM patients (91.8% vs. 99.1%, P < 0.001), but comparable to AML-BFM patients (87.9%). Event-free survival (EFS) and overall survival (OS) of ALAL patients were low, at 62 +/- 5%. 5-year probability of EFS was significantly worse than in ALL patients (80 +/- 1%, P < 0.001), but better than for AML patients (49 +/- 2%, P = 0.027). Our data suggest that an intensive therapy regimen including stem cell transplantation may be favourable for bilineal or lineage switch cases, whereas patients with ETV6/RUNX1 fusion, lymphoid morphology and patients with expression of cyCD22 and cyCD79a should be treated with an ALL-directed therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Child, Preschool
  • Chromosome Aberrations
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunophenotyping
  • Infant
  • Leukemia / diagnosis*
  • Leukemia / genetics
  • Leukemia / therapy
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome