Escalated daunorubicin dosing as an induction treatment for Philadelphia-negative adult acute lymphoblastic leukemia

Ann Hematol. 2013 Aug;92(8):1101-10. doi: 10.1007/s00277-013-1728-y. Epub 2013 Apr 5.

Abstract

The dose intensity of daunorubicin (DNR) delivered during the induction period represented the major prognostic factor for the outcome of adult acute lymphoblastic leukemia (ALL). The aim of this study was to determine the survival or toxicity of escalated doses of DNR in induction treatment of adult patients with acute lymphoblastic leukemia who are at least 15 years of age. For induction chemotherapy, all patients were given 90 mg/m(2)/day of DNR by continuous intravenous (IV) infusion over 24 h daily on days 1-3, 2 mg of vincristine IV push on days 1 and 8, and 60 mg/m(2)/day of prednisolone per oral (PO) on days 1-14 in conjunction with 4,000 units/m(2)/day of L-asparaginase intramuscular or subcutaneous on days 17-28. The median patient age was 32 years (range, 15-69). Complete remission (CR) was achieved in 169 (88.5 %) patients, while 4 died before CR was reached. Additionally, 11 patients died from leukemia progression, 4 had refractory disease, and 3 had follow-up loss. The median follow-up time was 697 days (range, 12-2,270). The 3-year cumulative incidence of relapse was 49.3 %. The probabilities of disease-free survival and overall survival at 3 years were 46.1 and 43.1 %, respectively. The dose of DNR was 100 % of the target dose, and there were no additional specific toxicities. The results show that escalated doses of DNR in induction chemotherapy are similar with the standard dose in response and toxicities. Our study indicates that a more effective regimen or better chemotherapy agents are needed to improve the CR rate and prolong survival in Philadelphia-negative adult ALL.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / administration & dosage
  • Asparaginase / adverse effects
  • Central Nervous System / pathology
  • Consolidation Chemotherapy
  • Cranial Irradiation
  • Daunorubicin / administration & dosage
  • Daunorubicin / adverse effects
  • Disease Progression
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / drug therapy*
  • Leukemic Infiltration / prevention & control
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Prednisolone / administration & dosage
  • Prednisolone / adverse effects
  • Recurrence
  • Remission Induction
  • Survival Rate
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Vincristine / adverse effects
  • Young Adult

Substances

  • Vincristine
  • Prednisolone
  • Asparaginase
  • Daunorubicin