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The effect of prolonged pulse therapy with vincristine and dexamethasone (VD) during maintenance therapy on the outcome of paediatric patients with TCF3-PBX1 positive acute lymphoblastic leukaemia (ALL) remains uncertain. We conducted non-inferiority analysis of 263 newly diagnosed TCF3-PBX1 positive ALL children who were stratified and randomly assigned (1:1) to receive seven additional VD pulses (the control group) or not (the experimental group) in the CCCG-ALL-2015 clinical trial from January 2015 to December 2019 (ChiCTR-IPR-14005706). There was no significant difference in baseline characteristics between the two groups. With a median follow-up of 4.2 years, the 5-year event-free survival (EFS) and 5-year overall survival (OS) in the control group were 90.1% (95% confidence interval [CI] 85.1-95.4) and 94.7% (95% CI, 90.9-98.6) comparable to those in the experimental group 89.2% (95% CI 84.1-94.7) and 95.6% (95% CI 91.8-99.6), respectively. Non-inferiority was established as a one-sided 95% upper confidence bound for the difference in probability of 5-year EFS was 0.003, and that for 5-year OS was 0.01 by as-treated analysis. Thus, omission of pulse therapy with VD beyond one year of treatment did not affect the outcome of children with TCF3-PBX1 positive ALL.

Summary We report the outcome of 92 non-high risk children with acute lymphoblastic leukaemia (ALL) following a Berlin-Frankfurt-Munster (BFM) Intercontinental ALL -based protocol. Compared with a matched historical control group, we found a lower incidence of treatment-related early death (1·2% vs. 10·9%, P = 0·015), a higher 6-year event-free survival (75·4 ± 4·9% vs. 58·2 ± 6·7%, P = 0·02), reduced total in-hospital costs per person (US $) (10267·0 vs. 18331·0, P

Cytosine arabinoside (ara-C) is irreversibly deaminated to a non-toxic metabolite by cytidine deaminase (CDA). A common polymorphism, A79C, in the gene encoding cytidine deaminase (CDA) changes a lysine residue to glutamine resulting in decreased enzyme activity. CDA A79C genotypes were determined in 457 children with acute myeloid leukaemia (AML) treated on the Children's Cancer Group (CCG) 2941 and 2961 protocols and analyzed the impact of CDA genotype on therapy outcomes. Postinduction treatment-related mortality (TRM) was significantly elevated in children with the CC genotype (5-year TRM 17 +/- 13% CC vs. 7 +/- 4% AA, 5 +/- 4% AC, P = 0.05). This was more notable in children who received idarubicin, fludarabine, ara-C, and granulocyte colony-stimulating factor (IDA-FLAG; ara-C = 7590 mg/m2) (5-year TRM 24 +/- 21% CC vs. 6 +/- 6% AA, 6 +/- 7% AC, P = 0.07) as consolidation therapy compared to idarubicin, dexamethasone, cytarabine, thioguanine, etoposide and daunomycin (IDA-DCTER; ara-C = 800 mg/m2) (5-year TRM 15 +/- 20% CC vs. 8 +/- 6% AA, 4 +/- 6% AC; P = 0.29). Relapse-free survival was non-significantly increased in children with the CC genotype treated with IDA-FLAG (76 +/- 20% CC vs. 59 +/- 12% AA and 55 +/- 14% AC; P = 0.40). These data indicate that children with a low activity CDA genotype are at increased risk of TRM with ara-C based therapy for AML.