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

P>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-Frankfurt-Munster (BFM) acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) studies between 1998 and 2006 (2 center dot 4% of all cases with acute leukaemia). Our cohort of ALAL patients was characterized by comparatively high median age (8 center dot 9 years), high median white blood cell count (14 center dot 9 x 109/l), as well as frequent hyperleucocytosis (18 center dot 5%) and central nervous system involvement (24 center dot 1%). The most frequent cytogenetic abnormalities were ETV6/RUNX1 fusion (16%) and trisomy 8 (14 center dot 6%). Complete remission rate was significantly lower than in ALL-BFM patients (91 center dot 8% vs. 99 center dot 1%, P < 0 center dot 001), but comparable to AML-BFM patients (87 center dot 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 center dot 001), but better than for AML patients (49 +/- 2%, P = 0 center dot 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.