Key Points• Childhood B-ALL patients, including those with VHR features, had favorable outcomes on DFCI 05-001 riskstratified therapy.• IKZF1 deletion was an independent predictor of inferior outcome, including among patients with low end-induction MRD. CI,[77][78][79][80][81][82][83][84][85][86][87][88], and VHR (N 5 65) was 79% (95% CI, 67-87). IKZF1 deletion was present in 62 of 385 (16%) assessed patients and was associated with inferior 5-year EFS (63%; 95% CI, 49%-74% vs 88%; 95% CI, 84%-91%; P , .001), and higher 5-year cumulative incidence of relapse, including among those with low MRD (24% vs 8%, P = .001). In multivariable analysis, age $15 years, WBC $50 3 10 9 /L, IKZF1 deletion, and MRD $10 24 was each associated with inferior outcome. In conclusion, risk-stratified therapy on DFCI 05-001 resulted in favorable outcomes for B-ALL patients, including those with VHR features. IKZF1deletion was an independent predictor of inferior outcome. This trial was registered at www.clinicaltrials.gov as #NCT00400946.

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Variants in SYNE2, MRPL47 and BAHD1 genes are putative new risk factors for VIPN in childhood acute lymphoblastic leukemia.