title: Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations.
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.
authors.affiliation: Department of Paediatric Haematology/Oncology, Hannover Medical School, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Gerr
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Michael
authors.initials: M
authors.lastname: Dworzak
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Ludwig
authors.forename: Jutta
authors.initials: J
authors.lastname: Bradtke
authors.forename: Anja
authors.initials: A
authors.lastname: Moericke
authors.forename: Richard
authors.initials: R
authors.lastname: Schabath
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007938:Leukemia / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome