Outcome of Adult ALL Patients with Fusion Transcript E2A-PBX1: Results from the GMALL Therapy Trials 5/93 and 6/99.

The chromosomal translocation t(1;19) with fusion transcript E2A-PBX1 is the third most prevalent recurrent translocation in adult ALL (after t(9;22) and t(4;11)), accounting for about 3% of all cases. It’s prognostic impact in adults has been controversially discussed and it has been suggested that this aberration might define a high risk patient group. However, this would be in contrast to the situation in pediatric ALL, where E2A-PBX1/t(1;19) meanwhile defines a patient group with a better than average outcome. We have investigated retrospectively by RT-PCR 337 B-precursor BCR-ABL-/MLL-AF4-negative ALL patients enrolled in the GMALL 5/93 and 6/99 therapy trials for the presence of this mRNA fusion transcript. This represents the largest cohort of adult BCR-ABL-negative patients investigated for E2A-PBX1 by RT-PCR thus far. We assessed the clinical characteristics of the E2A-PBX1-positive patients and their overall survival.

Results: Eighteen patients were E2A-PBX1-positive by RT-PCR (5.8% of the investigated group, roughly 3% of the total of all ALL patients). Fourteen had a pre B (cyIg+), and 4 a common immunophenotype. Twenty-two percent of all pre B ALL patients were E2A-PBX1-positive. The median age of the positive patients at diagnosis was 27 (15–60) years and the median leukocyte count was 36.700/μl (N=17) with 7 of 17 patients presenting with an initial leukocyte count >30.000/nl (59% vs 27% in the negative group, p=0.005). Compared to the E2A-PBX1-negative group (239 common, 49 pre B, 31 pro B, median age 32 years, median leukocyte count 11.900 (N=312) the E2A-PBX1-positive patients had a lower overall survival rate (0.33 vs. 0.36). The CR rate did not differ significantly between E2A-PBX1-positive and -negative patients.

These results support the assumption that in contrast to the situation in pediatric ALL E2A-PBX1 defines a relatively unfavourable genetic subgroup in adult ALL. It is strongly correlated with high leukocyte count (>30.000/μl) at diagnosis which is a highly significant poor prognostic factor in B-precursor ALL. It remains to be established whether E2A-PBX1 can be confirmed as an independent prognostic factor within standard risk B-precursor ALL. E2A-PBX1 may be useful to separate in so called standard risk ALL a patient group which may benefit from stem cell transplantation in first CR.