Key Points

  • Isolated CNS relapse was associated with male sex and BCR-ABL1 fusion in B-ALL and high presenting leukocyte count in T-ALL.

  • Upfront dexamethasone, delayed initial intrathecal therapy, anesthesia for procedure, and flow cytometry exam of CSF reduced CNS relapse.

To identify the prognostic factors that are useful to improve CNS control in children with acute lymphoblastic leukemia (ALL), we analyzed the outcome of 7640 consecutive patients treated on China Children's Cancer Group ALL-2015 protocol between 2015 and 2019. This protocol featured prephase dexamethasone treatment before conventional remission induction and subsequent risk-directed therapy, including 16 to 22 triple intrathecal treatments, without prophylactic cranial irradiation. The 5-year event-free survival was 80.3% (95% CI, 78.9%-81.7%), and overall survival 91.1% (95% CI, 90.1%-92.1%). The cumulative risk of isolated CNS relapse was 1.9% (95% CI, 1.5%-2.3%), and any CNS relapse 2.7% (95% CI, 2.2%-3.2%). The isolated CNS relapse rate was significantly lower in patients with B-ALL than in those with T-ALL (1.6%; 95% CI,1.2%-2.0% vs 4.6%; 95% CI 2.9%-6.3%; P <0.001). Independent risk factors for isolated CNS relapse included male sex (hazard ratio [HR], 1.8; 95% CI, 1.1%-3.0%; P=0.03), the presence of BCR-ABL1 fusion (HR, 3.8; 95% CI, 2.0%-7.3%; P <0.001) in B-ALL, and presenting leukocyte count ≥50×109/L (HR, 4.3; 95% CI, 1.5%-12.2%; P=0.007) in T-ALL. Significantly lower isolated CNS relapse was associated with the use of total intravenous anesthesia during intrathecal therapy (HR, 0.2; 95% CI, 0.04%-0.7%; P=0.02) and flow cytometry examination of diagnostic cerebrospinal fluid (HR, 0.2; 95% CI, 0.06%-0.6%; P=0.006) among patients with B-ALL. Prephase dexamethasone treatment, delayed intrathecal therapy, use of total intravenous anesthesia during intrathecal therapy, and flow cytometry examination of diagnostic cerebrospinal fluid may improve CNS control in childhood ALL.

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