United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia.
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.
Soignet
S L
SL
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
Frankel
S R
SR
Douer
D
D
Tallman
M S
MS
Kantarjian
H
H
Calleja
E
E
Stone
R M
RM
Kalaycio
M
M
Scheinberg
D A
DA
Steinherz
P
P
Sievers
E L
EL
Coutré
S
S
Dahlberg
S
S
Ellison
R
R
Warrell
R P
RP
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
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide