Delaying intrathecal therapy in leukemia may preclude need for cranial radiotherapy

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1. Delaying the first round of triple intrathecal therapy (TIT) until peripheral blasts were cleared improved CNS control in children with newly diagnosed acute lymphoblastic leukemia (ALL) and made cranial radiotherapy unnecessary.

Evidence rating level: 2 (Good)

Study Rundown: As the CNS provides a refuge for recurrent acute lymphoblastic leukemia (ALL), treatment of the CNS with cranial irradiation (CrRT) or triple intrathecal chemotherapy (TIT) is a key component in the management of these patients. However, both CrRT and traumatic lumbar puncture with TIT present significant risks to patients, both in the short and long-term picture. The purpose of this study was to examine the outcomes from a modified CNS-directed therapy in ALL, in which TIT is delayed until peripheral blasts are cleared.

At the conclusion of this prospective study, the authors found that the 5-year event-free survival and overall survival rates were >80% and >90%, respectively. There were two cases of combined CNS relapses and the 7-year cumulative risk of CNS relapse was 1.4%. Based on these results, the authors suggest that delaying the first round of TIT until peripheral blasts have been cleared may improve CNS control and preclude any need for CrRT. It should be noted that while this study benefits from a prospective design, it did not include a comparison group.

Click to read the study in JCO

Relevant Reading: Traumatic lumbar puncture at diagnosis and outcome in childhood acute lymphoblastic leukemia

In-Depth [prospective cohort]: This was a prospective cohort of 152 children with recently diagnosed ALL. All were treated with triple intrathecal therapy alone without CrRT. The first TIT was delayed until blasts had disappeared from peripheral blood for up to 10 days of multi-drug induction. TIT was performed if blasts persisted on treatment day 10. 5-year event-free survival and overall survival rates were 84.2% and 90.6%, respectively. Two patients experienced combined CNS relapses and no patients experienced an isolated CNS relapse. The 7-year cumulative risk of any CNS relapse was 1.4%.

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