• 1 Allen Eng Juh Yeoh, Yi Lu, Winnie Hui Ni Chin, Edwynn Kean Hui Chiew, Evelyn Huizi Lim, Zhenhua Li, Shirley Kow Yin Kham, Yiong Huak Chan, Poh Lin Tan, and Thuan Chong Quah, National University of Singapore; Allen Eng Juh Yeoh, Edwynn Kean Hui Chiew, Poh Lin Tan, and Thuan Chong Quah, National University Health System; Joyce Ching Mei Lam and Ah Moy Tan, KK Women's & Children's Hospital, Singapore; Wan Ariffin Abdullah and Hany Ariffin, University of Malaya, Kuala Lumpur; and Hai Peng Lin and Lee Lee Chan, Sime Darby Medical Centre Subang Jaya, Subang Jaya, Malaysia
J. Clin. Oncol., 2018 09 10;36(26):2726-2735.
PMID: 30044693 DOI: 10.1200/JCO.2018.78.3050


Purpose Although IKZF1 deletion ( IKZF1del) 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 IKZF1del 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 IKZF1del using the multiplex ligation-dependent probe amplification assay. The impact of IKZF1del on the 5-year cumulative incidence of relapse (CIR) was compared between the two studies. Results Patient characteristics were similar in both cohorts, including IKZF1del frequencies (59 of 410 [14.4%] v 50 of 275 [18.2%]; P = .2). In MS2003, where IKZF1del was not used in risk assignment, IKZF1del 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, IKZF1del conferred a higher 5-year CIR (20.5% v 8.0%; P = .01). In MS2010, the 5-year CIR of patients with IKZF1del 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 IKZF1del improved from 69.6% in MS2003 to 91.6% in MS2010 ( P = .007). Conclusion Intensifying therapy for childhood B-ALL with IKZF1del significantly reduced the risk of relapse and improved overall survival. Incorporating IKZF1del screening significantly improved treatment outcomes in contemporary ALL therapy.

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