Lineage classification of childhood acute lymphoblastic leukemia according to the EGIL recommendations: results of the ALL-BFM 2000 trial

Klin Padiatr. 2013 May:225 Suppl 1:S34-9. doi: 10.1055/s-0033-1337961. Epub 2013 May 22.

Abstract

Background: Flow cytometry immunophenotyping (FCM) is an undispensable tool for the diagnosis and for the treatment stratification of childhood acute lymphoblastic leukemia. The correlation of the EGIL-classification with prognostically relevant parameters like age, prednisone response and risk group is analyzed.

Patients: Between March 2000 and June 2009 12 patients less than 1 year of age, 1 836 patients with 1 to less than 6 years, 620 patients with 6 to less than 10 years, 615 patients with 10 to less than 15 years and 275 patients with 15 to less than 19 years were analyzed with a comprehensive 4-color antibody panel and classified according to the EGIL recommendations.

Methods: Bone marrow or peripheral blood mononuclear cells were isolated by ficoll gradient centrifugation, washed and stained with fluorochrome-conjugated antigen-specific monoclonal antibodies. Cell preparations were acquired and analyzed on a flow cytometer.

Results: Centralized FCM was performed for 2 775 patients (82.6%) with B-cell precursor acute lymphoblastic leukemia, 493 patients (14.7%) with T-cell acute lymphoblastic leukemia and 90 patients (2,7%) with biphenotypic acute leukemia. There was a slight overall predominance of male (56.1%) over female (43.9%) patients. Patients with B-cell precursor ALL had a slightly more favourable outcome with a 10 y pEFS of 78 ± 1.0%, compared to patients with a T-ALL or BAL (biphenotypic acute leukemia) phenotype with a 10 y pEFS of 74 ± 1.8% (n.s.) or 69 ± 9.0% (p<0.009), respectively.

Conclusions: FCM according to the EGIL recommendations not only provides diagnostic lineage determination and subclassification but also enables an initial prognostic orientation before MRD (minimal residual disease)-based risk stratification becomes available.

Publication types

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

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / adverse effects
  • Asparaginase / therapeutic use
  • Cell Lineage / genetics*
  • Child
  • Child, Preschool
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Cytarabine / adverse effects
  • Cytarabine / therapeutic use
  • Daunorubicin / adverse effects
  • Daunorubicin / therapeutic use
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Infant
  • Leukemia, Biphenotypic, Acute / classification
  • Leukemia, Biphenotypic, Acute / drug therapy*
  • Leukemia, Biphenotypic, Acute / genetics*
  • Leukemia, Biphenotypic, Acute / mortality
  • Male
  • Mercaptopurine / adverse effects
  • Mercaptopurine / therapeutic use
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use
  • Neoplasm, Residual / classification
  • Neoplasm, Residual / drug therapy
  • Neoplasm, Residual / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / classification
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / classification
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Prognosis
  • Survival Analysis
  • Vincristine / adverse effects
  • Vincristine / therapeutic use

Substances

  • Cytarabine
  • Vincristine
  • Cyclophosphamide
  • Mercaptopurine
  • Asparaginase
  • Prednisone
  • Methotrexate
  • Daunorubicin

Supplementary concepts

  • AIEOP acute lymphoblastic leukemia protocol