title: Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia.
abstract: OBJECTIVE
  Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patients with relapsed acute promyelocytic leukemia (APL). Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may strongly enhance the response to ATO.
  
  
  METHODS
  Between 1998 and 2001, we conducted a randomized study of ATO alone versus ATO plus ATRA in 20 patients with relapsed APL, all previously treated with ATRA-containing chemotherapy. The primary objective was to demonstrate a significant reduction in the time necessary to obtain a complete remission (CR) in the ATO/ATRA group compared with the ATO group. Secondary objectives were safety and molecular response.
  
  
  RESULTS
  The CR rate after one ATO with or without ATRA induction cycle was 80%. Clinical and pharmacokinetic observations indicated that the main mechanism of action of ATO in vivo was the induction of APL cell differentiation. Hematologic and molecular response, time necessary to reach CR, and outcome were comparable in both treatment groups. Of 16 CR patients, three patients who reached a molecular remission after one induction cycle had all received chemotherapy for a treatment-induced hyperleukocytosis. Three additional patients who received further additional ATO with or without ATRA cycles converted later to molecular negativity.
  
  
  CONCLUSIONS
  ATRA did not seem to significantly improve the response to ATO in patients relapsing from APL. Other potential combinations, including ATO plus chemotherapy, have to be tested.
authors.affiliation: Department and Institute of Hematology, Hôpital Saint-Louis, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Raffoux
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.forename: Jöel
authors.initials: J
authors.lastname: Poupon
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Daniel
authors.forename: Bruno
authors.initials: B
authors.lastname: Cassinat
authors.forename: Richard
authors.initials: R
authors.lastname: Delarue
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Taksin
authors.forename: Delphine
authors.initials: D
authors.lastname: Réa
authors.forename: Agnès
authors.initials: A
authors.lastname: Buzyn
authors.forename: Annick
authors.initials: A
authors.lastname: Tibi
authors.forename: Geneviève
authors.initials: G
authors.lastname: Lebbé
authors.forename: Patricia
authors.initials: P
authors.lastname: Cimerman
authors.forename: Christine
authors.initials: C
authors.lastname: Chomienne
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fermand
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
authors.forename: Laurent
authors.initials: L
authors.lastname: Degos
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage; D012008:Recurrence; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D001152:Arsenicals; D010087:Oxides; D014212:Tretinoin; D000077237:Arsenic Trioxide