title: Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia.
abstract: We examined whether combining all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) might be an alternative to ATRA plus chemotherapy in untreated acute promyelocytic leukemia (APL). Twenty-five low-risk patients (white blood cell [WBC] count less than 10 x 10(9)/L [10,000/microL]) received ATRA (45 mg/m(2) daily) and ATO (0.15 mg/kg daily, beginning day 10 of ATRA), and in complete remission (CR) received ATO plus ATRA, without chemotherapy, unless they were reverse transcriptase-polymerase chain reaction (RT-PCR)-positive 3 months from CR date or had molecular relapse. Nineteen high-risk patients were treated identically, but received chemotherapy, generally 9 mg/m(2) gemtuzumab ozogamycin (GO) on day 1 of induction. The CR rate was 39 of 44 (24 of 25 in low-risk, 15 of 19 in high-risk). Disease recurred at 9, 9, and 15 months, respectively, in 3 high-risk patients. The median follow-up time from CR date in the 36 patients alive in first CR is 16 months (15 months in low-risk, 20 months in high-risk), with 9 patients followed for at least 24 months. Each of the 36 patients was PCR-negative at last follow-up. Thus, none of the low-risk patients has received chemotherapy, and only 3 high-risk patients (the 3 with relapsed disease) have received chemotherapy past induction. ATRA plus ATO may serve as an alternative to chemotherapy in low-risk untreated APL (eg, in older patients) and, when combined with GO, may improve outcome in high-risk patients.
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Box 428, Houston, 77030, USA. ehestey@mdanderson.org
authors.forename: Elihu
authors.initials: E
authors.lastname: Estey
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010087:Oxides / Q000008:administration & dosage* / Q000009:adverse effects; D016133:Polymerase Chain Reaction; D012074:Remission Induction; D014212:Tretinoin / Q000008:administration & dosage*
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001152:Arsenicals; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D010087:Oxides; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D000079982:Gemtuzumab; D000077237:Arsenic Trioxide