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 Sep 10;36(26):2726-2735. doi: 10.1200/JCO.2018.78.3050. Epub 2018 Jul 25.
Purpose Although IKZF1 deletion ( IKZF1) 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 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 using the multiplex ligation-dependent probe amplification assay. The impact of IKZF1 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 frequencies (59 of 410 [14.4%] v 50 of 275 [18.2%]; P = .2). In MS2003, where IKZF1 was not used in risk assignment, IKZF1 conferred a significantly higher 5-year CIR (30.4% v 8.1%; P = 8.7 × 10), 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 conferred a higher 5-year CIR (20.5% v 8.0%; P = .01). In MS2010, the 5-year CIR of patients with IKZF1 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 improved from 69.6% in MS2003 to 91.6% in MS2010 ( P = .007). Conclusion Intensifying therapy for childhood B-ALL with IKZF1 significantly reduced the risk of relapse and improved overall survival. Incorporating IKZF1 screening significantly improved treatment outcomes in contemporary ALL therapy.
目的
尽管 IKZF1 缺失（IKZF1）会增加儿童 B 细胞急性淋巴细胞白血病（B-ALL）复发的风险，但尚不确定强化治疗是否会逆转这种风险并改善预后。马来西亚-新加坡 ALL 2010 研究（MS2010）前瞻性地将 IKZF1 患者的风险分配升级到下一个更高的水平，并在所有 BCR-ABL1 融合患者中添加伊马替尼。
患者和方法
共有 823 名接受马来西亚-新加坡 ALL 2003 研究（MS2003；n = 507）和 MS2010（n = 316）治疗的 B-ALL 患者接受了 IKZF1 的多重连接依赖性探针扩增检测。比较了这两项研究中 IKZF1 对 5 年累积复发率（CIR）的影响。
结果
两个队列的患者特征相似，包括 IKZF1 频率（410 例中的 59 例[14.4%]与 275 例中的 50 例[18.2%]；P =.2）。在 MS2003 中，未将 IKZF1 用于风险分配，IKZF1 导致 5 年 CIR 显著升高（30.4%比 8.1%；P =.7×10），尤其是在缺乏高危特征的中危组（25.0%比 7.5%；P =.01）。对于 BCR-ABL1 阴性疾病患者，IKZF1 导致 5 年 CIR 更高（20.5%比 8.0%；P =.01）。在 MS2010 中，IKZF1 患者的 5 年 CIR 显著下降至 13.5%（P =.05），而在 BCR-ABL1 阴性疾病患者中，差异不再显著（11.4%比 4.4%；P =.09）。IKZF1 患者的 5 年总生存率从 MS2003 的 69.6%提高到 MS2010 的 91.6%（P =.007）。
结论
强化治疗儿童 B-ALL 伴 IKZF1 显著降低了复发风险，提高了总生存率。纳入 IKZF1 筛查显著改善了当代 ALL 治疗的疗效。
