title: Augmented therapy improves outcome for pediatric high risk acute lymphocytic leukemia: results of Children's Oncology Group trial P9906.
abstract: BACKGROUND
  The augmented BFM regimen improves outcome for children with NCI high acute lymphoblastic leukemia (ALL). Patient age, sex, and presenting white blood cell count (WBC) can be used to identify a subset of approximately 12% of children with B-precursor ALL that had a 5-year continuous complete remission (CCR) rate of only about 50% on earlier Pediatric Oncology Group (POG) trials.
  
  
  METHODS
  Children's Oncology Group trial P9906 evaluated a modified augmented BFM regimen in 267 patients with particularly high risk B-precursor ALL. Minimal residual disease (MRD) was assessed in blood at day 8 and in marrow at day 29 of induction and correlated with outcome.
  
  
  RESULTS
  The 5-year CCR probability for patients in P9906 was significantly better than that observed for similar patients on POG trials 8602/9006 (62.2 ± 3.7% vs. 50.6 ± 2.4%; P = 0.0007) but similar to POG 9406 (63.5 ± 2.4%; P = 0.81). Interim analysis showed poor central nervous system (CNS) control, especially in patients with initial WBC ≥ 100,000/microliter. Day 29 marrow MRD positive (≥ 0.01%) vs. negative patients had 5 year CCR rates of 37.1 ± 7.4% vs. 72.6 ± 4.3%; day 8 blood MRD positive vs. negative patients had 5 year CCR rates of 57.1 ± 4.6% vs.83.6 ± 6.3%. End induction marrow MRD predicted marrow but not CNS relapse. In multivariate analysis, day 29 MRD > 0.01%, initial WBC ≥ 100,000/µl, male gender, and day 8 blood MRD > 0.01% were significant prognostic factors.
  
  
  CONCLUSIONS
  Augmented BFM therapy improved outcome for children with higher risk ALL. Day 8 blood and day 29 marrow MRD were strong prognostic factors in these patients.
authors.affiliation: Cook Children's Hospital, Fort Worth, Texas, USA.
authors.forename: W Paul
authors.initials: WP
authors.lastname: Bowman
authors.forename: Eric L
authors.initials: EL
authors.lastname: Larsen
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Linda
authors.forename: Laurie
authors.initials: L
authors.lastname: Blach
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: D Jeanette
authors.initials: DJ
authors.lastname: Pullen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shuster
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Willman
authors.forename: Naomi
authors.initials: N
authors.lastname: Winick
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Camitta
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Borowitz
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D013866:Thioguanine / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D003520:Cyclophosphamide; D015122:Mercaptopurine; D001215:Asparaginase; D013866:Thioguanine; D011241:Prednisone; D008727:Methotrexate; D003630:Daunorubicin