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Purpose   Although IKZF1 deletion ( IKZF1 del ) confers a higher risk of relapse in childhood B-cell acute lymphoblastic leukemia (B-ALL), it is uncertain whether treatment intensification will reverse this risk and improve outcomes. The Malaysia-Singapore ALL 2010 study (MS2010) prospectively upgraded the risk assignment of patients with IKZF1 del  to the next highest level and added imatinib to the treatment of all patients with BCR- ABL1 fusion.Patients and Methods   In total, 823 patients with B-ALL treated in the Malyasia-Singapore ALL 2003 study (MS2003; n = 507) and MS2010 (n = 316) were screened for IKZF1 del  using the multiplex ligation-dependent probe amplification assay. The impact of IKZF1 del  on the 5-year cumulative incidence of relapse (CIR) was compared between the two studies.Results   Patient characteristics were similar in both cohorts, including IKZF1 del  frequencies (59 of 410 [14.4%] v 50 of 275 [18.2%]; P = .2). In MS2003, where IKZF1 del  was not used in risk assignment, IKZF1 del  conferred a significantly higher 5-year CIR (30.4% v 8.1%; P = 8.7 × 10 −7 ), particularly in the intermediate-risk group who lacked high-risk features (25.0% v 7.5%; P = .01). For patients with BCR-ABL1–negative disease, IKZF1 del  conferred a higher 5-year CIR (20.5% v 8.0%; P = .01). In MS2010, the 5-year CIR of patients with IKZF1 del  significantly decreased to 13.5% ( P = .05) and no longer showed a significant difference in patients with BCR-ABL1-negative disease (11.4% v 4.4%; P = .09). The 5-year overall survival for patients with IKZF1 del  improved from 69.6% in MS2003 to 91.6% in MS2010 ( P = .007).Conclusion   Intensifying therapy for childhood B-ALL with IKZF1 del  significantly reduced the risk of relapse and improved overall survival. Incorporating IKZF1 del  screening significantly improved treatment outcomes in contemporary ALL therapy.

journal of clinical oncology

Intensifying Treatment of Childhood B-Lymphoblastic Leukemia With <i>IKZF1</i> Deletion Reduces Relapse and Improves Overall Survival: Results of Malaysia-Singapore ALL 2010 Study

Intensifying Treatment of Childhood B-Lymphoblastic Leukemia With IKZF1 Deletion Reduces Relapse and Improves Overall Survival: Results of Malaysia-Singapore ALL 2010 Study