Prognosis of pediatric BCP-ALL with IKZF1 deletions and impact of intensive chemotherapy: Results of SCCLG-2016 study

Background

IKZF1 deletion (IKZF1^del) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1^del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined.

Methods

A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1^del patients were further divided based on chemotherapy intensity for outcome assessments.

Results

The BCP-ALL pediatric patients with IKZF1^del in south China showed poorer early response. Notably, the DFS and OS for IKZF1^del patients were markedly lower than IKZF1^wt group (3-year DFS: 88.7% [95% CI: 83.4%–94.0%] vs. 93.5% [95% CI: 92.0%–94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%–10.5%] vs. 2.9% [95% CI: 1.9%–3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%–9.5%] vs. 3.7% [95% CI: 2.6%–4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1^del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1^del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026).

Conclusions

Pediatric BCP-ALL patients with IKZF1^del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1^del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1^del subset, particularly in IKZF^del patients with BCR::ABL positive.