What is the best intrathecal therapy for children with acute lymphoblastic leukemia?

This study aimed to investigate if postinduction central nervous system (CNS; brain and spine) protection with intrathecal (injection into the spine) triple therapy (ITT) would improve the outcomes for pediatric patients with acute lymphoblastic leukemia (ALL) when compared to intrathecal methotrexate (MTX; Otrexup) treatment.  

This study concluded that ITT did not improve outcomes for these patients when compared to intrathecal MTX therapy.  

Children with ALL are at risk of cancer returning to the brain. This is mainly because standard chemotherapy cannot get into the CNS and kill cancer cells that may be hiding in there. Therefore, after first therapy (induction therapy), CNS protection therapy is given by intrathecal (IT) injection. IT involves injecting drugs into the spinal canal. 

Standard CNS protection therapy involves either MTX-IT injection or intrathecal triple therapy (ITT). ITT involves MTX, cytarabine (Cytosar-U), and hydrocortisone (Hydrocort). Both therapies have reduced CNS relapse rates in children with standard-risk (SR) ALL. However, it was unknown if ITT provided better outcomes for children with high-risk (HR) ALL when compared to IT-MTX.  

This study involved 1734 pediatric patients with newly diagnosed HR B-cell ALL (B-ALL). Patients received postinduction IT MTX (868) or ITT (866) for a total of 21 to 26 doses.  

The 5-year disease-free survival (DFS) rate for the IT MTX group was 93.2% compared to 90.6% for the ITT group. The 5-year overall survival (OS) rate was 96.3% for the IT MTX group compared to 96.7% for the ITT group.  

There were no differences in isolated bone marrow relapse, isolated CNS relapse, combined bone marrow, and CNS relapse rates between the IT MTX and ITT groups.  

There were no significant differences in the neurological side effects and neurocognitive (related to thinking and reasoning) outcomes for patients receiving IT MTX compared with ITT. 

This study concluded that ITT did not improve outcomes for children with HR ALL. The authors suggested that the standard of care treatment for these patients should remain IT MTX.