Arsenic trioxide during consolidation for patients with previously untreated low/intermediate risk acute promyelocytic leukaemia may eliminate the need for maintenance therapy

Br J Haematol. 2014 May;165(4):497-503. doi: 10.1111/bjh.12775. Epub 2014 Feb 14.

Abstract

Aa total of 105 patients (age ≥18 years) with newly diagnosed low or intermediate risk acute promyelocytic leukaemia (APL) were treated with a standard induction and consolidation regimen including arsenic trioxide (ATO). Sixty-eight patients who were polymerase chain reaction (PCR) negative for PML-RARA post-consolidation were randomized to either 1 year of maintenance with tretinoin, mercaptopurine and methotrexate, or observation. Enrollment in this non-inferiority trial was stopped prematurely due to slow accrual. With a median follow up of 36·1 months, the overall survival of the 105 patients was 93%, and there have been no relapses in the patients randomized to maintenance or observation. These results demonstrate that cures can be expected in >90% of patients with low and intermediate risk APL and suggest that maintenance therapy may not be needed if patients are treated with an intensive post-remission regimen including ATO. This trial was registered at clinicaltrials.gov as #NCT00492856.

Keywords: acute promyelocytic leukaemia; leukaemia clinical; leukaemia trials; malignant haematology.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aminoglycosides / administration & dosage
  • Aminoglycosides / adverse effects
  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Arsenic Trioxide
  • Arsenicals / administration & dosage
  • Arsenicals / adverse effects
  • Biomarkers, Tumor
  • Consolidation Chemotherapy*
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Daunorubicin / administration & dosage
  • Daunorubicin / adverse effects
  • Disease-Free Survival
  • Dogs
  • Female
  • Gemtuzumab
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Maintenance Chemotherapy
  • Male
  • Mercaptopurine / administration & dosage
  • Mercaptopurine / adverse effects
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Middle Aged
  • Oncogene Proteins, Fusion / blood
  • Oxides / administration & dosage
  • Oxides / adverse effects
  • Platelet Count
  • Remission Induction
  • Risk
  • Treatment Outcome
  • Tretinoin / administration & dosage
  • Tretinoin / adverse effects
  • Young Adult

Substances

  • Aminoglycosides
  • Antibodies, Monoclonal, Humanized
  • Arsenicals
  • Biomarkers, Tumor
  • Oncogene Proteins, Fusion
  • Oxides
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • Cytarabine
  • Tretinoin
  • Gemtuzumab
  • Mercaptopurine
  • Arsenic Trioxide
  • Methotrexate
  • Daunorubicin

Associated data

  • ClinicalTrials.gov/NCT00492856

Grants and funding