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


Authors: Soignet, S. L.; Frankel, S. R.; Douer, D.; Tallman, M. S.; Kantarjian, H.; Calleja, E.; Stone, R. M.; Kalaycio, M.; Scheinberg, D. A.; Steinherz, P.; Sievers, E. L.; Coutré, S.; Dahlberg, S.; Ellison, R.; Warrell, R. P. Jr
Article Title: United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia
Abstract: 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 ≥ 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/μL) 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. © 2001 by American Society of Clinical Oncology.
Keywords: adolescent; adult; cancer survival; clinical article; middle aged; survival analysis; unclassified drug; clinical trial; fatigue; diarrhea; dose response; drug efficacy; drug safety; antineoplastic agents; united states; reverse transcription polymerase chain reaction; peripheral neuropathy; relapse; cytogenetics; dexamethasone; allogenic bone marrow transplantation; coughing; rash; arsenic trioxide; chemotherapy induced emesis; hypokalemia; arsenicals; leukemia, promyelocytic, acute; oxides; reverse transcriptase polymerase chain reaction; pilot projects; syndrome; multicenter study; acute myeloblastic leukemia; remission; remission induction; seizure; headache; bone marrow cell; alitretinoin; electrocardiography; leukocytosis; electrocardiogram; retinoic acid; tachycardia; platelet count; lung hemorrhage; autologous bone marrow transplantation; retinoic acid receptor alpha; retinoic acid receptor; torsade des pointes; nervous system diseases; qt interval; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 19
Issue: 18
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2001-09-15
Start Page: 3852
End Page: 3860
Language: English
PUBMED: 11559723
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 21 May 2015 -- Source: Scopus