title: United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia.
abstract: OBJECTIVE
  To determine the safety and efficacy of arsenic trioxide (ATO) in patients with relapsed acute promyelocytic leukemia (APL).
  
  
  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.
  
  
  CONCLUSIONS
  This study establishes ATO as a highly effective therapy for patients with relapsed APL.
authors.affiliation: Leukemia and Developmental Chemotherapy Services, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Joan and Sanford Weill Medical College of Cornell University, New York, NY 10021, USA. soignets@mskcc.org
authors.forename: S L
authors.initials: SL
authors.lastname: Soignet
authors.forename: S R
authors.initials: SR
authors.lastname: Frankel
authors.forename: D
authors.initials: D
authors.lastname: Douer
authors.forename: M S
authors.initials: MS
authors.lastname: Tallman
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
authors.forename: E
authors.initials: E
authors.lastname: Calleja
authors.forename: R M
authors.initials: RM
authors.lastname: Stone
authors.forename: M
authors.initials: M
authors.lastname: Kalaycio
authors.forename: D A
authors.initials: DA
authors.lastname: Scheinberg
authors.forename: P
authors.initials: P
authors.lastname: Steinherz
authors.forename: E L
authors.initials: EL
authors.lastname: Sievers
authors.forename: S
authors.initials: S
authors.lastname: Coutré
authors.forename: S
authors.initials: S
authors.lastname: Dahlberg
authors.forename: R
authors.initials: R
authors.lastname: Ellison
authors.forename: R P
authors.initials: RP
authors.lastname: Warrell
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects / Q000627:therapeutic use*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D007964:Leukocytosis / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D010087:Oxides / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D010976:Platelet Count; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013577:Syndrome
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide