Chemotherapy Regimen Positively Impacts Survival for Children and Adolescents with Leukemia

Study establishes new treatment standard for patients with the most common form of children's cancer.   

Bethesda, MD – Findings released today at the American Society for Clinical Oncology conference establish new treatment standards for patients with acute lymphoblastic leukemia (ALL), a fast growing cancer of white blood cells diagnosed in more than 4,000 children and adolescents each year.

The randomized Phase III trial demonstrated improved five year, relapse-free survival when using a chemotherapy agent called methotrexate in high doses in children and young adults.  Methotrexate is delivered intravenously and for more than 50 years, has been an essential component in treating children with ALL.  However, the optimal dose and when in treatment it is administered has been a matter of debate and clinical research.  

For the last 20 years, increasing intravenous methotrexate based on the patient's tolerance, followed by a second chemotherapy drug called asparaginase, has been the standard treatment for ALL.  While the current treatment of methotrexate and asparaginase has led to improved cure rates for ALL, relapse rates in the central nervous system (CNS) have not declined as significantly, representing an ongoing need for better treatment options.

To reduce these CNS relapses, the study findings released today tested a methotrexate regimen which delivers a dose 50 times the starting dose of the escalating regimen.  The hypothesis was that doing so would increase the chance that methotrexate would infiltrate the central nervous system.

"Pediatric ALL was once a deadly form of leukemia, and now it's one of the most curable. 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," said Eric C. Larsen, MD, principal investigator of the study and director of the Maine Children's

Cancer Program and the Division of Pediatric Hematology/Oncology at the Barbara Bush Children's Hospital at Maine Medical Center. "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."

The Phase III study, conducted by the Children's Oncology Group and funded by CureSearch for Children's Cancer and the National Cancer Institute, randomized 2,426 patients ages 1 to 30 with newly diagnosed high-risk B-precursor ALL to high-dose methotrexate versus escalating methotrexate plus asparaginase during a two-month interim maintenance phase of therapy following standard induction and consolidation chemotherapy.
At a planned interim analysis, the five-year, event-free survival for patients who received high-dose methotrexate was 82%, compared to 75% for patients on the escalating methotrexate regimen. There were also significantly fewer bone marrow and CNS relapses in the high-dose group. Enrollment was halted early as a result, and certain patients were eligible to then receive the high dose methotrexate regimen off protocol.

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About CureSearch for Children's Cancer
CureSearch for Children's Cancer is a not-for-profit foundation which funds the lifesaving, collaborative research of the Children's Oncology Group, the largest children's cancer research organization in the world. With more than 210 member hospitals world wide and 6,500 physicians, nurses and researchers, member hospitals treat more than 90 percent of children with cancer in the U.S.  For more information, visit

Study Information
83893 (Larsen, Plenary): High dose methotrexate (HD-MTX) as compared to Capizzi methotrexate plus asparaginase (C-MTX/ASNase) improves event-free survival (EFS) in children and young adults with high-risk acute lymphoblastic leukemia (HR-ALL):  a report from the Children's Oncology Group study AALL0232


Christine Bork
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