"With a cure rate approaching  percent acute lymphoblastic leukemia ALL  the most common type of childhood cancer  is often hailed as one of the success stories of modern cancer treatment. But up to  percent of patients with a high risk of relapse are not cured. That could change with the results from a clinical trial coled by investigators from NYU Langone Medical Center which shows giving high doses of a commonlyused chemotherapy drug increases the survival rate for these patients.  The highdose methotrexate protocol outlined in the study  along with a parallel finding that the steroid decadron is beneficial for younger but not older patients  has quickly become the standard practice for the treatment of highrisk ALL patients in North America the researchers report in the April XX issue of the Journal of Clinical Oncology. For more than  years ALL patients have been treated with a combination of steroids and methotrexate among other agents. Patients classified as high risk for relapsethose with a high white blood cell count or who are more than  years oldare treated with a standard phase of therapy where methotrexate is given in a gradual escalating dosage. The current study showed that an alternative schedule of highdose methotrexate was superior. Prior to the release of the initial study results which were first presented last year at the annual meeting of the American Society of Clinical Oncology ASCO the standard of care for highrisk ALL patients in North America was escalating methotrexate. One of the improvements in outcome for ALL overall has been using methotrexate in a more intense fashion by giving higher doses said senior investigator William L. Carroll MD the Julie and Edward J. Minskoff Professor of Pediatrics director of the Stephen D. Hassenfeld Childrens Center for Cancer and Blood Disorders at NYU Langone and director emeritus of NYU Langones Perlmutter Cancer Center. 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 highrisk ALL patients. This was a largescale study involving pediatric cancer centers across the country. More than  patients with highrisk ALL were enrolled in the randomized clinical trial which was run by the Childrens Oncology Group a multiinstitutional clinical trials consortium supported by the National Cancer Institute. The investigators found that patients in either arm responded very well overall to treatments but those in the high dose group had a significantly better outcome by  to  percent which translated into a significantly decreased relapse rate for these patients. The clinical protocol also examined how to best use a steroid formulation called decadron to treat highrisk ALL patients. Steroids as a class of drugs are one of the most effective medications in the treatment of ALL. Previous studies by the Childrens Oncology Group showed that in standard risk ALL patientsthose with low white blood cell counts or under  years of agedecadron prevented relapse in both the spinal fluid and in the bone marrow. Decadron however can increase the infection rate particularly in highrisk ALL patients when given for the full day induction period. During this clinical trial the investigators decreased the duration of decadron from  days to  to determine if patients could avoid the side effect of increased infection while still benefiting from the steroids antileukemic effects. They found that patients  years and older saw no benefit from decadron and in fact were at much higher risk for a debilitating bone condition called osteonecrosis. Patients under  years of age however did benefit from the shorter decadron exposure with no increased side effects. 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 said. 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. Dr. Carrolls coauthors are Eric C. Larsen at Maine Childrens Cancer Program Scarborough ME Meenakshi Devidas and Si Chen at the University of Florida Wanda L. Salzer at the U.S. Army Medical Research and Materiel Command Fort Detrick MD James B. Nachman at the University of Chicago Elizabeth A. Raetz at the University of Utah Mignon L. Loh at the Benioff Childrens Hospital and the University of California San Francisco Leonard A. Mattano Jr. at HARP Pharma Consulting Catherine Cole at Princess Margaret Hospital for Children and University of Western Australia Alisa Eicher at Doernbecher Childrens Hospital Portland OR Maureen Haugan at Ann and Robert H. Lurie Childrens Hospital of Chicago Mark Sorenson at University of Iowa Hospitals and Clinics Nyla A. Heerema and Julie M. GastierFoster at The Ohio State University School of Medicine Andrew A. Carroll at the University of Alabama at Birmingham Michael J. Borowitz at Johns Hopkins Medical Institutions Brent L. Wood at University of Washington Cheryl L. Willman at University of New Mexico Naomi J. Winick at University of Texas Southwestern Medical Center Dallas and Stephen P. Hunger at Childrens Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania. The research was supported by the National Institutes of Health and the National Cancer Institute."