Li and colleagues report the genomic landscape of over 100 patients with relapsed acute lymphoblastic leukemia. Analysis of diagnosis-relapse-remission trios suggest that whereas early relapse is mediated by retained subclones, late relapse is driven by mutations induced by and conferring resistance to chemotherapy.

IMPORTANCEA randomized clinical trial is needed to determine whether the second-generation Abl-tyrosine kinase inhibitor dasatinib is more effective than the first-generation inhibitor imatinib mesylate for childhood Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).OBJECTIVE To determine whether dasatinib given at a daily dosage of 80 mg/m 2 is more effective than imatinib mesylate at a daily dosage of 300 mg/m 2 to improve event-free survival of children with Philadelphia chromosome-positive ALL in the context of intensive chemotherapy without prophylactic cranial irradiation. DESIGN, SETTING, AND PARTICIPANTSThis open-label, phase 3 randomized clinical trial was conducted at 20 hospitals in China. Enrollment occurred from January 1, 2015, through September 18, 2018, and randomization was stopped on October 4, 2018, when the early stopping criterion of the trial was met. Patients aged 0 to 18 years were recruited. Of the 225 patients with the diagnosis, 35 declined participation and 1 died before treatment, leaving 189 patients available for analysis. Data were analyzed from January 1 through August 4, 2019. INTERVENTIONS Patients were randomized to receive daily dasatinib (n = 92) or imatinib (n = 97) continuously for the entire duration of ALL therapy from the time of diagnosis made during remission induction to the end of continuation therapy. MAIN OUTCOMES AND MEASURESThe primary outcome was event-free survival, analyzed based on intention to treat. The secondary outcomes were relapse, death due to toxic effects, and overall survival. RESULTS Among the 189 participants (136 male [72.0%]; median age, 7.8 [interquartile range (IQR), 5.2-11.3] years) and a median follow-up of 26.4 (IQR,) months, the 4-year event-free survival and overall survival rates were 71.0% (95% CI, 56.2%-89.6%) and 88.4% (95% CI, 81.3%-96.1%), respectively, in the dasatinib group and 48.9% (95% CI, 32.0%-74.5%; P = .005, log-rank test) and 69.2% (95% CI, 55.6%-86.2%; P = .04, log-rank test), respectively, in the imatinib group. The 4-year cumulative risk of any relapse was 19.8% (95% CI, 4.2%-35.4%) in the dasatinib group and 34.4% (95% CI, 15.6%-53.2%) in the imatinib group (P = .01, Gray test), whereas the 4-year cumulative risk of an isolated central nervous system relapse was 2.7% (95% CI, 0.0%-8.1%) in the dasatinib group and 8.4% (95% CI, 1.2%-15.6%) in the imatinib group (P = .06, Gray test). There were no significant differences in the frequency of severe toxic effects between the 2 treatment groups.CONCLUSIONS AND RELEVANCE Intensive chemotherapy including dasatinib at a dosage of 80 mg/m 2 per day yielded superior results in the treatment of Philadelphia chromosome-positive ALL compared with imatinib mesylate at a dosage of 300 mg/m 2 per day and provided excellent control of central nervous system leukemia without the use of prophylactic cranial irradiation.

ObjectivesBefore 2003, most children with acute lymphoblastic leukaemia (ALL) abandoned treatment, with only approximately 30% treated in China. With the development of national insurance for underprivileged patients, we assessed the current frequency and causes of treatment abandonment among patients with ALL who were enrolled in the Chinese Children’s Cancer Group ALL protocol between 2015 and 2016.MethodsDemographic, clinical and laboratory data on patients who abandoned treatment, as well as economic and sociocultural data of their families were collected and analysed. General health-related statistics were retrieved from publicly accessible databanks maintained by the Chinese government.ResultsAt a median follow-up of 119 weeks, 83 (3.1%, 95% CI 2.5% to 3.8%) of the 2641 patients abandoned treatment. Factors independently associated with abandonment included standard/high-risk ALL (OR 2.62, 95% CI 1.43 to 4.77), presence of minimal residual disease at the end of remission induction (OR 3.57, 95% CI 1.90 to 6.74) and low-income economic region (OR 3.7, 95% CI 1.89 to 7.05). According to the family members, economic constraints (50.6%, p=0.0001) were the main reason for treatment abandonment, followed by the belief of incurability, severe side effects and concern over late complications.ConclusionsThe rate of ALL treatment abandonment has been greatly reduced in China. Standard/high-risk ALL, residence in a low-income region and economic difficulties were associated with treatment abandonment.Clinical trial registration numberChiCTR-IPR-14005706, pre-results.