Background: IKZF1deletion is an unfavorable factor in Philadelphia negative (Ph ‐) B‐cell acute lymphoblastic leukemia. However, the effects of IKZF1 deletions co‐existing genetic alterations in Ph (‐) ALL have not been extensively studied.Methods: Bone marrow samples from 368 children with Ph (‐) ALL were analyzed by using multiplex ligation‐dependent probe amplification kit for detection of gene deletions and Sanger sequencing for mutational analysis of RAS pathway genes. The outcome was analyzed on 215 patients treated with Taiwan Pediatric Oncology Group‐ALL‐2002 protocol.Results: IKZF1 deletions were present in 12.8% and IKZF1^plus in 6.3% of patients. Mutations of RAS pathway genes were detected in 25.0% of IKZF1‐deleted patients. The 10‐year event‐free survival (EFS) of IKZF1‐undeleted patients was significantly better compared with IKZF1‐deleted patients (80.0% vs. 47.8%, p = 0.001). Compared with outcome of patients harboring IKZF1 deletion alone, no difference in EFS was observed in patients with IKZF1^plus, whereas three patients carried both IKZF1 and ERG deletions had a superior 10‐year EFS (100%). The 10‐year EFS of patients with any gene mutation of RAS pathway was worse than that of patients with wild‐type genes (79.1% vs. 61.6%, p = 0.033). In multivariate analysis, RAS pathway mutations and IKZF1 deletion were independent predictors of inferior EFS. Co‐existence of IKZF1 deletion with RAS pathway mutations had a worst 10‐year EFS (11.1 ± 10.5%) and 10‐year OS (53.3 ± 17.6%).Conclusions: Our results showed that RAS pathway mutation is an added‐value biomarker in pediatric IKZF1‐deleted Ph (‐) ALL patients.

Pediatric extracranial germ cell tumors (GCTs) are rare, accounting for approximately 3.5% of childhood cancers. Since the introduction of platinum-based chemotherapy, the survival rate of patients has improved to more than 80%. However, poor-risk subtypes of pediatric extracranial GCTs do not respond well to chemotherapy, leading to refractory or relapsed (R/R) diseases. For example, long-term survival rates of mediastinal GCTs or choriocarcinoma are less than 50%. According to reports in recent years for adult patients with R/R GCTs, the use of high-dose chemotherapy (HDCT) combined with autologous stem cell transplantation (ASCT) has clinical advantages; however, HDCT combined with ASCT has rarely been reported in pediatric GCTs. The R/R and poor-risk groups of pediatric GCTs could benefit from HDCT and ASCT.