Higher Doses of Chemotherapy Drug Could Reduce Relapse Rates of Childhood Leukemia

In a new study, researchers found that higher doses of methotrexate increase survival and decrease relapse in high-risk patients with acute lymphoblastic leukemia (ALL).

Patients classified as high risk for relapse have a high white blood count or are over 10-years-old, according to the study published by the Journal of Clinical Oncology.

These patients are currently being treated with methotrexate in gradual, escalating doses.

"One of the improvements in outcome for ALL overall has been using methotrexate in a more intense fashion, by giving higher doses," said senior researcher William L. Carroll, MD. "We designed this study to compare high dose and escalating methotrexate to determine the best way to use this drug to increase the survival of high-risk ALL patients."

The randomized clinical trial included more than 3000 high-risk ALL patients.

Researchers found that patients receiving the higher dosage of methotrexate had a better outcome by 5 to 6%, which means these patients had a decreased relapse rate compared with patients receiving standard treatment.

The study also evaluated how to use the steroid decadron effectively to treat these high-risk patients. According to the study, decadron prevented relapse in the spinal fluid and in the bone marrow, but can also increase infection rate in high-risk ALL patients during the 28-day induction period.

Researchers decreased the duration of this drug from 28 to 14 days in order to see if patients would avoid the side effects, but also benefit from the drug.

Patients 10 years and older did not benefit from decadron and were at a higher risk of developing osteonecrosis.

Patients under 10 years old did benefit from the drug with no increased side effects, according to the study.

"The improvement in cure rates for ALL over the last few decades, for the most part, has not come through the introduction of new medications, but through using existing medications in new ways, in terms of their dose and schedule," Dr. Carroll concluded. "This clinical trial illustrates that despite what seem to be remarkable outcomes for kids with ALL, we have not reached a plateau. The outcomes are getting better and better."