Arsenic trioxide at conventional dosage does not aggravate hemorrhage in the first-line treatment of adult acute promyelocytic leukemia

Eur J Haematol. 2018 Apr;100(4):344-350. doi: 10.1111/ejh.13018. Epub 2018 Feb 9.

Abstract

Objectives: The arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) therapy has demonstrated a tremendous success in the first-line treatment of acute promyelocytic leukemia (APL). Actually, early death (ED) is currently thought as a major challenge in APL. ATO has been reported to inhibit platelet function in vitro, and whether it increases the ED rate by exacerbating the hemorrhagic symptoms remains to be investigated.

Methods: Effects of ATO on platelet aggregation and adhesion were evaluated in vitro and in thirty-two complete remission (CR) and four newly diagnosed APL patients. Furthermore, concentrations of plasma total arsenic were monitored in APL patients via ICP-MS.

Results: The inhibition of platelet function, either aggregation or adhesion, did occur in vitro when the concentration of ATO reached 2 μmol/L. However, in CR APL patients receiving ATO with normal platelet count, the platelets responded normally when being activated and so did those in the newly diagnosed patients with thrombocytopenia. Our data further showed that the conventional dosage of ATO reached a plasma concentration substantially below the required concentration to inhibit platelets.

Conclusions: In the first-line treatment of APL, the use of ATO is safe and effective and does not compromise the hemostatic potential that may eventually increase ED rate.

Keywords: acute promyelocytic leukemia; arsenic trioxide; early death; platelet function.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Arsenic Trioxide
  • Arsenicals / administration & dosage*
  • Arsenicals / adverse effects
  • Arsenicals / pharmacokinetics
  • Blood Coagulation / drug effects
  • Female
  • Hemorrhage / etiology*
  • Hemorrhage / mortality
  • Humans
  • Leukemia, Promyelocytic, Acute / blood
  • Leukemia, Promyelocytic, Acute / complications*
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Oxides / administration & dosage*
  • Oxides / adverse effects
  • Oxides / pharmacokinetics
  • Platelet Adhesiveness / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Function Tests
  • Remission Induction
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Arsenicals
  • Oxides
  • Arsenic Trioxide