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

J Clin Oncol. 2008 Jan 10;26(2):283-9. doi: 10.1200/JCO.2007.12.3927.

Abstract

Purpose: 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.

Patients and 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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / therapeutic use
  • Chi-Square Distribution
  • Child, Preschool
  • Combined Modality Therapy
  • Cranial Irradiation
  • Cyclophosphamide / therapeutic use
  • Cytarabine / therapeutic use
  • DNA, Neoplasm / analysis
  • Daunorubicin / therapeutic use
  • Female
  • Humans
  • Infant
  • Italy
  • Male
  • Mercaptopurine / therapeutic use
  • Methotrexate / therapeutic use
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Prednisone / therapeutic use
  • Prognosis
  • Remission Induction
  • Survival Rate
  • Treatment Outcome
  • Vincristine / therapeutic use

Substances

  • DNA, Neoplasm
  • Cytarabine
  • Vincristine
  • Cyclophosphamide
  • Mercaptopurine
  • Asparaginase
  • Prednisone
  • Methotrexate
  • Daunorubicin

Supplementary concepts

  • AIEOP acute lymphoblastic leukemia protocol