Clinical sensitivity to anthracyclines in PH/BCR+ acute lymphoblastic leukemia

Adv Exp Med Biol. 1999:457:489-99. doi: 10.1007/978-1-4615-4811-9_53.

Abstract

Translocation t(9;22) or Philadelphia chromosome (Ph)/BCR-ABL rearrangement positive acute lymphoblastic leukemia (Ph/BCR+ ALL) is associated with a very short survival of about one year in most patients. We analyzed long-term outcome of 76 adults with Ph/BCR+ ALL, in order to detect which factors were associated with longer survival. Modifiable prognostic factors included type of treatment, allogeneic marrow transplant (allo-BMT), and early anthracycline dose intensity (high = H/A, low = L/A); unmodifiable factors were age, gender, FAB morphology, phenotype, blast count, P190/210 transcript, hepatospleno-lymphadenopathy, LDH level. Median patient age was 43 years (range 15-71). Four favorable prognostic factors (FPF) were found associated with greater likelihood of complete remission (blast count < 50 x 10(9)/l, p = 0.08), longer remission duration (age < 50 years, p < 0.001; H/A, p < 0.05), and lower relapse rate (allo-BMT, p = 0.017). Age and anthracycline dose intensity exerted a synergistic prognostic effect. According to the cumulative incidence of FPF in each patient (FPF 0-1 = 29, 2-3 = 42, 4 = 5), the probability of survival increased from nil to 0.22 to 0.60 at 5 years (p < 0.005). Adult Ph/BCR+ ALL is relatively sensitive to anthracyclines, which therefore should be prescribed at full dosage to patients not eligible to allo-BMT or in the waiting list for unrelated donor transplantation.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Blast Crisis / immunology
  • Blast Crisis / pathology
  • Chromosomes, Human, Pair 22
  • Chromosomes, Human, Pair 9
  • Female
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / genetics
  • Gene Rearrangement
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prognosis
  • Survival Rate
  • Time Factors
  • Translocation, Genetic

Substances

  • Fusion Proteins, bcr-abl