Long-term efficacy of low-dose all-trans retinoic acid plus minimal chemotherapy induction followed by the addition of intravenous arsenic trioxide post-remission therapy in newly diagnosed acute promyelocytic leukaemia

Hematol Oncol. 2014 Mar;32(1):40-6. doi: 10.1002/hon.2076. Epub 2013 Aug 20.

Abstract

We evaluated the efficacy of low-dose all-trans retinoic acid (ATRA) plus minimal chemotherapy for induction in newly diagnosed acute promyelocytic leukaemia (APL). Furthermore, we compared its long-term outcome with or without the addition of intravenous arsenic trioxide (ATO) in post-remission therapy. From January 2004 to September 2011, a total of 109 patients with a median age of 41 years (range 14-73) were enrolled in the study. Two arms were assigned according to post-remission protocols: ATO group cases were subsequently treated with intravenous ATO, standard chemotherapy, and ATRA. No-ATO group cases were subsequently treated with chemotherapy and ATRA only. Patients were monitored of minimal residual disease (MRD) by reverse-transcriptase polymerase chain reaction. The haematologic complete remission (CR) rate was 96.3%. The early death rate was 0.9%. At a median follow-up of 49 months (range 8-102 months), the Kaplan-Meier estimates of 5-year relapse-free survival were significantly better for patients in the ATO group than in the no-ATO group, 94.4% vs 54.8% (p = 0.0001), and the 5-year overall survival rate was 95.7% vs 64.1%, in the two groups (p = 0.003). Our data show that low-dose ATRA plus minimal chemotherapy exhibits efficacy in induction therapy for untreated APL and suggest that the addition of ATO to post-remission therapy significantly improves the long-term outcome.

Keywords: acute promyelocytic leukaemia; all-trans retinoic acid; arsenic trioxide; long-term survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Arsenic Trioxide
  • Arsenicals / administration & dosage
  • China
  • Consolidation Chemotherapy
  • Cytarabine / administration & dosage
  • Daunorubicin / administration & dosage
  • Dexamethasone / administration & dosage
  • Drug Evaluation
  • Female
  • Harringtonines / administration & dosage
  • Homoharringtonine
  • Humans
  • Idarubicin / administration & dosage
  • Infusions, Intravenous
  • Kaplan-Meier Estimate
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / genetics
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Neoplasm, Residual
  • Oncogene Proteins, Fusion / genetics
  • Oxides / administration & dosage
  • Recurrence
  • Remission Induction
  • Retrospective Studies
  • Salvage Therapy
  • Treatment Outcome
  • Tretinoin / administration & dosage
  • Young Adult

Substances

  • Arsenicals
  • Harringtonines
  • Oncogene Proteins, Fusion
  • Oxides
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • Cytarabine
  • Tretinoin
  • Homoharringtonine
  • Dexamethasone
  • Arsenic Trioxide
  • Methotrexate
  • Idarubicin
  • Daunorubicin