title: Long-term results of the AIEOP-ALL-95 Trial for Childhood Acute Lymphoblastic Leukemia: insight on the prognostic value of DNA index in the framework of Berlin-Frankfurt-Muenster based chemotherapy.
abstract: OBJECTIVE
  Between May 1995 and August 2000 the Associazione Italiana di Ematologia Oncologia Pediatrica conducted the ALL-95 study for risk-directed, Berlin-Frankfurt-Muenster (BFM) -oriented therapy of childhood acute lymphoblastic leukemia, aimed at exploring treatment reduction in standard-risk patients (SR) and intensification during continuation therapy in intermediate-risk patients (IR) as randomized questions and treatment intensification in high-risk patients (HR). The prognostic value of DNA index was explored in this setting.
  
  
  METHODS
  A total of 1,744 patients were enrolled (115, SR; 1,385, IR; and 244, HR). SR patients (DNA index >/= 1.16 and < 1.60; age, 1 to 5 years; and WBC < 20,000, non-T-immunophenotype, with no high-risk features) received a reduced induction therapy (no anthracyclines); IR patients were randomly assigned to receive or not receive vincristine and dexamethasone pulses during maintenance; HR therapy was based on a conventional BFM schedule intensified with three chemotherapy blocks followed by a double reinduction phase.
  
  
  RESULTS
  The event-free survival and overall survival probabilities at 10 years for the entire group were 72.5% (SE, 1.3) and 83.6% (SE, 0.9); 85.0% (SE, 3.4) and 95.5% (SE, 2.0) in SR, 75.1% (SE, 1.5) and 87.5% (SE, 0.9) in IR, and 51.0% (SE, 3.2) and 57.2% (SE, 3.3) in HR patients, respectively. Patients with a favorable DNA index had superior EFS in both IR (83.8% [2.7%] v 73.9% [1.7%]) and in HR (67.8% [9.4%] and 49.6% [3.5%]). Of the six patients with DNA index less than 0.8, only one remained in remission.
  
  
  CONCLUSIONS
  Favorable DNA index was associated with a better prognosis in IR and HR patients defined by presenting clinical criteria and treatment with a BFM-oriented chemotherapy.
authors.affiliation: Pediatric Hematology Oncology, Ospedale dei Bambini G. Di Cristina, Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rizzari
authors.forename: Elena
authors.initials: E
authors.lastname: Barisone
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Fiorina
authors.initials: F
authors.lastname: Casale
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Luca
authors.initials: L
authors.lastname: Lo Nigro
authors.forename: Matteo
authors.initials: M
authors.lastname: Luciani
authors.forename: Chiara
authors.initials: C
authors.lastname: Messina
authors.forename: Concetta
authors.initials: C
authors.lastname: Micalizzi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Parasole
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Nicola
authors.initials: N
authors.lastname: Santoro
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Testi
authors.forename: Daniela
authors.initials: D
authors.lastname: Silvestri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Masera
authors.forename: Valentino
authors.initials: V
authors.lastname: Conter
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000627:therapeutic use; D016009:Chi-Square Distribution; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000032:analysis; D003630:Daunorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D004273:DNA, Neoplasm; D003561:Cytarabine; D014750:Vincristine; D003520:Cyclophosphamide; D015122:Mercaptopurine; D001215:Asparaginase; D011241:Prednisone; D008727:Methotrexate; D003630:Daunorubicin