United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia

J Clin Oncol. 2001 Sep 15;19(18):3852-60. doi: 10.1200/JCO.2001.19.18.3852.


Purpose: To determine the safety and efficacy of arsenic trioxide (ATO) in patients with relapsed acute promyelocytic leukemia (APL).

Patients and methods: Forty patients experiencing first (n = 21) or > or = second (n = 19) relapse were treated with daily infusions of ATO to a maximum of 60 doses or until all leukemic cells in bone marrow were eliminated. Patients who achieved a complete remission (CR) were offered one consolidation course of ATO that began 3 to 4 weeks later. Patients who remained in CR were eligible to receive further cycles of ATO therapy on a maintenance study.

Results: Thirty-four patients (85%) achieved a CR. Thirty-one patients (91%) with CRs had posttreatment cytogenetic tests negative for t(15;17). Eighty-six percent of the patients who were assessable by reverse transcriptase polymerase chain reaction converted from positive to negative for the promyelocytic leukemia/retinoic acid receptor-alpha transcript by the completion of their consolidation therapy. Thirty-two patients received consolidation therapy, and 18 received additional ATO as maintenance. Eleven patients underwent allogeneic (n = 8) or autologous (n = 3) transplant after ATO treatment. The 18-month overall and relapse-free survival (RFS) estimates were 66% and 56%, respectively. Twenty patients (50%) had leukocytosis (> 10,000 WBC/microL) during induction therapy. Ten patients developed signs or symptoms suggestive of the APL syndrome and were effectively treated with dexamethasone. Electrocardiographic QT prolongation was common (63%). One patient had an absolute QT interval of > 500 msec and had an asymptomatic 7-beat run of torsades de pointe. Two patients died during induction, neither from drug-related causes.

Conclusion: This study establishes ATO as a highly effective therapy for patients with relapsed APL.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Arsenic Trioxide
  • Arsenicals / adverse effects
  • Arsenicals / therapeutic use*
  • Electrocardiography
  • Female
  • Humans
  • Leukemia, Promyelocytic, Acute / blood
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / pathology
  • Leukocytosis / chemically induced
  • Male
  • Middle Aged
  • Nervous System Diseases / chemically induced
  • Oxides / adverse effects
  • Oxides / therapeutic use*
  • Pilot Projects
  • Platelet Count
  • Remission Induction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Syndrome


  • Antineoplastic Agents
  • Arsenicals
  • Oxides
  • Arsenic Trioxide