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

Abstract

SummaryAcute 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 (2AE4% of all cases with acute leukaemia). Our cohort of ALAL patients was characterized by comparatively high median age (8AE9 years), high median white blood cell count (14AE9 · 10 9 /l), as well as frequent hyperleucocytosis (18AE5%) and central nervous system involvement (24AE1%). The most frequent cytogenetic abnormalities were ETV6/RUNX1 fusion (16%) and trisomy 8 (14AE6%). Complete remission rate was significantly lower than in ALL-BFM patients (91AE8% vs. 99AE1%, P < 0AE001), but comparable to AML-BFM patients (87AE9%). 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 < 0AE001), but better than for AML patients (49 ± 2%, P = 0AE027). 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.

Lineage switch in childhood acute leukemia: An unusual event with poor outcome

“…In our experience, even when chemotherapy was administered based on immunophenotype findings, this strategy has not overcome the dismal prognosis in any of our patients. However, our cases are somewhat different from those reported by Gerr et al [37], mainly regarding cytogenetics and age. The authors reported that only the three cases with trisomy 8 remained alive following HSCT.…”

“…The mostly single case pediatric reports in the literature also support this notion, describing switches from Bcp to myelo-monocytic lineages [5,6,9,25,26,[31][32][33][34][35][36][37]. Conversions from AML (or bilineal) to ALL are even more rare [38][39][40][41][42][43], also involve mostly Bcp and myelo-monocytic lineages, as was the case with the 2 patients from our own series that switched from myeloid to Pro-B.…”

“…Treatment recommendations for lineage switch leukemia have been proposed in a recent publication: these patients should be initially treated according to phenotype and the therapy changed to the respectively other treatment following the lineage conversion [37]. In our experience, even when chemotherapy was administered based on immunophenotype findings, this strategy has not overcome the dismal prognosis in any of our patients.…”

“…However, there are also few communications involving T and myeloid lineages in adults [44][45][46]. A recent report by Gerr et al [37] about ambiguous lineage leukemias in children included eight cases of lineage conversion. However, these cases were not described in detail.…”

“…However, these cases were not described in detail. The authors pointed out that seven switched from lymphoid Bcp to myeloid and one from T to myeloid lineage; that three of them disclosed trisomy 8 and only one case had alterations involving the MLL gene [37]. Several hypotheses have been proposed for explaining lineage conversions.…”