Evaluating outcomes after higher doses of PEG-asparaginase and intense intrathecal therapy in children with high-risk acute lymphoblastic leukemia

This study investigated if a higher dose of PEG-asparaginase (Oncaspar) with early induction and additional triple intrathecal therapy (TIT) can prevent relapse in the brain in children with acute lymphoblastic leukemia (ALL). The authors found that additional TIT during early induction improved the outcomes of these patients, without added side effects.

Around 10% of children with ALL experience relapse after conventional chemotherapy. Standard treatment for children with ALL and high risk for relapse in the brain was radiotherapy at the head area. However, this was associated with long-term side effects. Recent studies have shown a reduction of brain leukemia relapse in these patients after using TIT. TIT involves injecting medications into the spinal canal. TIT with methotrexate (Otrexup), hydrocortisone (Hydrocort) and cytarabine (Cytosar-U) is used to kill any cancer cells spread to the brain.

PEG-asparaginase is a chemotherapy drug that blocks the growth of cancer cells. Previous studies showed that the conventional dose of PEG-asparaginase can only prevent the relapse of cancer in blood but not in the brain. It is still unknown if higher doses of PEG-asparaginase and more intense TIT would improve the outcomes of children with ALL and high risk of brain relapse.

598 patients aged 18 years or younger with newly diagnosed ALL were included in this study. Patients were divided into three groups based on the risk of relapse (low-risk, standard-risk and high-risk). Patients were given during induction treatment (the first treatment given to kill leukemia cells) either the conventional dose of PEG-asparaginase (2,500 U/m²) or a higher dose (3,500 U/m²) among other standard chemotherapy drugs. High-risk patients received two additional doses of TIT during induction treatment. Patients were followed up for an average of 6.26 years.

For all patients, the rate of survival without any complications from the disease was 88.2% at 5 years. The 5-year overall survival was 94.1%, with a 1.5% risk of relapse in the brain.

98.66% of all patients were in remission after induction treatment. Among patients who received the standard PEG-asparaginase dose, 90.4% were in complete remission after 5 years. This was compared to 91.2% in the higher PEG-asparaginase group.

High-risk patients who received more intense TIT had a significantly lower risk of relapse in brain (1.8%) compared to those in a previous study where two extra doses of intrathecal treatment were avoided (5.7%). There were no differences in side effects between patients who received standard and intensified TIT.

The study concluded that higher doses of PEG-asparaginase did not add more benefit to the outcomes of children with ALL in children. However, the early induction and additional TIT safely reduced the relapse of ALL in the brain of high-risk patients.

This study compared TIT among patients in two different studies. This might have affected the results. More studies are needed for stronger evidence.