ABSTRACT
INTRODUCTION: Worldwide, the B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) treatment protocols are based on risk-adaptive therapy, that is on the search for biological markers for stratification by risk groups for optimal management. Depending on the treatment protocol, deletions and overexpression of non-functional IKZF1 isoforms act as relapse predictors in ALL. We investigated the IKZF1 gene aberrations as the substantive marker for predicting the development of relapse or adverse events when using risk stratification from ALL-MB-2002/2008 protocols. METHODS: We retrospectively analysed the bone marrow samples collected from 202 newly diagnosed patients with BCP-ALL harbouring IKZF1 aberrations. RESULTS: In patients of intermediate- and high-risk the presence of IKZF1 aberrations contributed to the delayed clearance of blast cells on the 15th and 36th day of induction therapy, but there was not a significant effect on relapse rate. The comparative analysis demonstrated that standard-risk patients with IKZF1 aberrations have a much higher 5-years cumulative incidence of relapse (66.7 ± 22.7% vs. 11.6 ± 2.9% in the group with normal gene status, p < 0.001) in contrast to intermediate- and high-risk groups. In the competing risk model of relapse, IKZF1 aberrations determine a high risk of relapse only in standard-risk patients (p = 0.025), and it was not significant for patients of other risk groups (p = 0.284 for intermediate, and 0.408 for high-risk groups). CONCLUSION: Our findings support that IKZF1 aberrations are a crucial relapse predictor in standard-risk patients with BCP-ALL, who practically have no significant markers to assess the prognosis during the primary diagnosis.
