Treatment Timing and Other Prognostic Factors Associated With Reduction in CNS Relapse Risk for Pediatric ALL

Prognostic factors including treatment timing, total intravenous anesthesia, and flow cytometry were associated with a reduced risk of central nervous system (CNS) relapse for pediatric patients with acute lymphoblastic leukemia (ALL), according to data published in Blood.

More, beginning chemotherapy several days prior to the first lumbar puncture for diagnosis and treatment of ALL could also reduce the risk of CNS relapse for this cohort of patients.

“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,” wrote the investigative team in their assessment of the data.

The investigators analyzed the outcomes of 7640 consecutive patients treated between 2015 and 2019 on China Children's Cancer Group ALL-2015 protocol. They worked to identify prognostic factors associated with improvements in CNS control.

The investigators found the 5-year event-free survival was 80.3% (95% CI, 78.9%-81.7%), with an overall survival rate of 91.1% (95% CI, 90.1%-92.1%) for the main cohort of patients.

Looking at CNS relapse risk for patients, the cumulative risk of isolated CNS relapse was 1.9% (95% CI, 1.5%-2.3%), with an any CNS relapse rate of 2.7% (95% CI, 2.2-3.2). More, this isolated CNS relapse rate was found to be significantly lower for patients with B-cell ALL (1.6%; 95% CI, 1.2%-2.0%) compared with patients with T-cell ALL (4.6%; 95% CI, 2.9%-6.3%; P < .001).

Independent risk factors that were associated with isolated CNS relapse included male sex (HR, 1.8; 95% CI, 1.1-3.0; P = .03), BCR-ABL1 fusion presence in B-cell ALL (HR, 3.8; 95% CI, 2.0-7.3; P < .001), and a presenting leukocyte count of 50 × 109/L or more in T-cell ALL (HR, 4.3; 95% CI, 1.5-12.2; P = .007).

Specifically, among patients with B-cell ALL, total intravenous anesthesia use during intrathecal therapy (HR, 0.2; 95% CI, 0.04-0.7; P = .02) and examining flow cytometry of diagnostic cerebrospinal fluid (HR, 0.2; 95% CI, 0.06-0.6; P = .006) were both associated with significantly lower isolated CNS relapse.

The research design adapted the treatment protocol seen in recent St. Jude clinical trials. The cohort of patients were treated across 20 different medical centers and hospitals across China with widely different technologies and clinical resources available.

Understanding the increase in pediatric patients with ALL who become long-term survivors requires knowledge of CNS relapse risk and how to prevent it, according to the corresponding author of the research, Ching-Hon Pui, MD, chair of the St. Jude Department of Oncology.

Reference:

Tang J, Yu J, Cai J, et al. Prognostic Factors for CNS Control in Children with Acute Lymphoblastic Leukemia Treated Without Cranial Irradiation. Blood. Published March 8, 20201. doi:10.1182/blood.2020010438