title: Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: POG 9406: a report from the Children's Oncology Group.
abstract: OBJECTIVE
  To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy.
  
  
  RESULTS
  Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase.
  
  
  CONCLUSIONS
  Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.
authors.affiliation: *MACC Fund Center for Cancer and Blood Disorders, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, WI †Department of Biostatistics, Colleges of Medicine and Public Health and Health Professions ††Department of Health Outcomes and Policy and Clinical and Translational Science Institute, College of Medicine, University of Florida ¶Children's Oncology Group, Department of Biostatistics, Gainesville, FL ‡Department of Pediatrics, Golisano Children's Hospital at University of Rochester Medical Center, Rochester #New York Medical College, Valhalla, NY §Department of Pediatrics, Georgia Health Sciences University, Augusta, GA ∥Department of Pediatrics, Charleston Division, West Virginia University, Charleston, WV **Department of Pediatric Hematology/Oncology, University of Mississippi Medical Center, Jackson, MS ‡‡Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX §§Pediatric Blood and Marrow Transplant Program, Duke University Medical Center, Durham, NC.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Tower
authors.forename: Tamekia L
authors.initials: TL
authors.lastname: Jones
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Camitta
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Asselin
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Bell
authors.forename: Allen
authors.initials: A
authors.lastname: Chauvenet
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Edward C
authors.initials: EC
authors.lastname: Halperin
authors.forename: Jeanette
authors.initials: J
authors.lastname: Pullen
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: Naomi
authors.initials: N
authors.lastname: Winick
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D002648:Child; D003561:Cytarabine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D013713:Teniposide / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D013713:Teniposide; D001215:Asparaginase; D008727:Methotrexate