Prognostic significance and treatment strategies for IKZF1 deletion in pediatric B-cell precursor acute lymphoblastic leukemia

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The predictive importance of IKZF1 del in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has shown variability across different studies. Thus, the optimal treatment approach for children with IKZF1 del BCP-ALL remains contentious, with the ongoing debate surrounding the use of IKZF1 del -based high-risk stratification versus a minimal residual disease (MRD)-guided protocol. IKZF1 status was reliably determined in 804 patients using multiplex ligation-dependent probe amplification (MLPA) data obtained from four hospitals in Fujian, a province of China. In the Chinese Children Leukemia Group (CCLG)-ALL 2008 cohort, IKZF1 status was included in the risk assignment, with all IKZF1 del patients receiving a high-risk regimen. Conversely, in the Chinese Children’s Cancer Group (CCCG)-ALL 2015 cohort, IKZF1 del was not incorporated into the risk assignment, and patients were treated based on an MRD-guided risk stratification protocol. IKZF1 del was found in 86 patients (86/804, 10.7%) overall and in 30 (30/46, 65.2%) BCR::ABL1 -positive patients. Overall, IKZF1 del was a poor prognostic predictor for patients, though the significance diminished upon age adjustment, white blood cell (WBC) count at diagnosis, treatment group, and MRD status. In the CCLG-ALL 2008 cohort, IKZF1 del conferred a notably lower 5-year overall survival (OS) and event-free survival (EFS) and a significantly higher 5-year cumulative incidence of relapse (CIR) than IKZF1 wt . In the CCLG-ALL 2015 cohort, IKZF1 del conferred a lower 5-year OS and EFS and a higher 5-year CIR than IKZF1 wt , but the differences were insignificant. The IKZF1 del patients treated with higher intensity chemotherapy (CCLG-ALL 2008 high-risk regimen) had a markedly lower 5-year OS and EFS compared with those treated with the MRD-guided protocol (CCCG-ALL 2015 protocol). Furthermore, patients treated with the CCLG-ALL 2008 high-risk regimen experienced a higher frequency of serious adverse events (SAEs), especially infection-related SAEs, compared with those treated with the CCCG-ALL 2015 MRD-guided protocol. The prognostic effect of IKZF1 del may vary in different protocols. Compared with higher intensity chemotherapy, the MRD-guided protocol may be a more effective approach to treating BCP-ALL with IKZF1 del in children.

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