Prediction of outcome by early response in childhood acute lymphoblastic leukemia

Klin Padiatr. 2013 May:225 Suppl 1:S50-6. doi: 10.1055/s-0033-1337964. Epub 2013 May 22.

Abstract

Background: In the ALL-BFM studies for treatment of acute lymphoblastic leukemia, reduction of leukemic blasts in peripheral blood after a one-week prednisone pre-phase - the so-called prednisone response - has been used for risk stratification since the 1980s and has been one of the most relevant factors for identification of high-risk patients. In the trial ALL-BFM 95, early cytomorphological marrow response on day 15 of induction therapy was prospectively evaluated and its prognostic value was analyzed in comparison to the prednisone response and other established prognostic factors.

Results: Compared to prednisone response, day 15 marrow response was superior in outcome prediction - yet with differential effect depending on blast lineage. Outcome was poor in T cell leukemia patients with prednisone poor-response independent of day 15 marrow response, whereas among patients with prednisone good-response different risk groups could be identified by day 15 marrow response. In contrast, prednisone response lost prognostic significance in precursor B cell leukemia when stratified by day 15 marrow response.

Conclusions: Selective addition of day 15 marrow response to conventional stratification criteria applied on ALL-BFM 95 may significantly improve risk-adapted treatment delivery. Even though cutting-edge trial risk stratification is meanwhile dominated by minimal residual disease evaluation, an improved conventional risk assessment, as presented here, could be of great importance to countries lacking the technical and/or financial resources associated with the application of minimal residual disease analysis.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / adverse effects
  • Asparaginase / therapeutic use
  • Biopsy
  • Bone Marrow / drug effects
  • Bone Marrow / pathology
  • Cell Lineage / drug effects
  • Child
  • Child, Preschool
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Cytarabine / adverse effects
  • Cytarabine / therapeutic use
  • Daunorubicin / adverse effects
  • Daunorubicin / therapeutic use
  • Disease-Free Survival
  • Female
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Mercaptopurine / adverse effects
  • Mercaptopurine / therapeutic use
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use
  • Patient Outcome Assessment*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Prognosis
  • Prospective Studies
  • Remission Induction
  • Risk Assessment
  • Vincristine / adverse effects
  • Vincristine / therapeutic use

Substances

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

Supplementary concepts

  • AIEOP acute lymphoblastic leukemia protocol