High-dose methotrexate improved EFS in children, adolescents with ALL

Issue: July 25, 2011

2011 ASCO Annual Meeting

CHICAGO — Compared with the standard treatment for high-risk acute lymphoblastic leukemia in children and young adults, high-dose methotrexate improved event-free survival and did not increase the number of significant side effects, according to data from a Children’s Oncology Group study presented here today.

“Pediatric ALL was once a deadly form of leukemia, and now it’s one of the most curable,” Eric C. Larsen, MD, director of the Maine Children’s Cancer Program at the Division of Pediatric Hematology/Oncology at the Barbara Bush Children’s Hospital at Maine Medical Center, and corresponding author, said in a press release. “This trial helps us address an important need for patients with this disease. With these results, we now have an approach that will raise cure rates even higher,” he said. “Based on the findings from this trial all current and upcoming treatment protocols for children with newly diagnosed high-risk B-precursor ALL will use this regimen.”

Larsen and colleagues conducted AALL0232, a phase 3 study to examine the safety and efficacy of interventions designed to enhance CNS control in these patients. The researchers compared high-dose methotrexate with Capizzi escalating methotrexate plus PEG asparaginase during interim maintenance-1 and dexamethasone vs. prednisone during induction.

The study included 2,426 patients aged from 1 to 30 years with newly diagnosed NCI high-risk B-precursor ALL. Patients were randomly assigned to dexamethasone vs. prednisone during induction and methotrexate 5 gm/m² biweekly x 4 vs. Capizzi methotrexate plus asparaginase during interim maintenance-1.

Five-year event-free survival was superior in the high-dose methotrexate group (82 + 3.4%) compared with the Capizzi methotrexate plus asparaginase group (75.4 + 3.6%; P=.006). Based on these data, enrollment was halted and patients in the C-MTX/ASNase group were crossed over to the high-dose methotrexate group when possible.

Marrow and CNS relapses occurred less often in the methotrexate group compared with the C-MTX/ASNase groups (42 and 22 events vs. 68 and 32 events). In addition, febrile neutropenia incidence was lower in the methotrexate group vs. C-MTX group (5.2% vs. 8.2%; P=.005). Clinically relevant toxicities, including acute neurotoxicity and osteonecrosis, were not statistically significantly different between the two groups, according to the researchers. – by Stacey L. Fisher

Disclosure: Dr. Larsen reports no relevant financial disclosures.

For more information:

Larsen EC. #3. Presented at: 2011 ASCO Annual Meeting; Chicago; June 3-7, 2011.

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