title: Thrombosis in patients with acute promyelocytic leukemia treated with and without all-trans retinoic acid.
abstract: Laboratory evidence of disseminated intravascular coagulation (DIC) and/or fibrinolysis is present in the majority of patients with acute promyelocytic leukemia (APL). Historically, early hemorrhagic death (EHD) occurred in 10% to 30% of patients treated with chemotherapy. All-trans retinoic acid (ATRA), a differentiating agent, has a CR rate above 80% in patients, with ATRA-associated leukocytosis. We studied thrombotic events in this population and compared it to patients treated with chemotherapy alone. The results of studies using ATRA in patients with APL were reviewed. Patients received ATRA 45-50 mg/m(2) orally in two divided doses daily until complete remission. In newly diagnosed patients, Idarubicin 12 mg/m(2)/day was given intravenously for 4 to 5 days beginning on the fifth day of ATRA therapy or when the white blood cell count (WBC) was over 10x 10(3)/mu l. Thrombotic complications were noted in 3 of 31 patients during induction. Two died from thrombotic events during therapy with multiple thromboses documented at autopsy. ATRA syndrome was suspected in 2 of the patients with thromboses and only 1 of the patients without thrombosis. In previous studies, 1 of 25 APL patients treated with chemotherapy alone had thrombotic events during therapy. In conclusion, treatment of APL with ATRA may decrease the incidence of hemorrhagic complications, but does not eliminate thrombosis. While thrombotic events were not significantly increased in patients treated with ATRA, they were more common in patients suspected of having ATRA syndrome.
authors.affiliation: Department of Hematology, Leukemia Section, University of Texas M.D. Anderson Cancer Center, Houston, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Escudier
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: E H
authors.initials: EH
authors.lastname: Estey
mesh_terms: D000328:Adult; D000677:Amsacrine / Q000008:administration & dosage; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000209:etiology; D015331:Cohort Studies; D003561:Cytarabine / Q000008:administration & dosage; D004211:Disseminated Intravascular Coagulation / Q000209:etiology / Q000517:prevention & control; D017809:Fatal Outcome; D005260:Female; D018237:Germinoma; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D015255:Idarubicin / Q000627:therapeutic use*; D015994:Incidence; D007238:Infarction / Q000209:etiology; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications* / Q000188:drug therapy; D007964:Leukocytosis / Q000139:chemically induced; D008297:Male; D008545:Melanoma; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D009378:Neoplasms, Multiple Primary / Q000150:complications / Q000188:drug therapy / Q000628:therapy; D012074:Remission Induction; D012189:Retrospective Studies; D013154:Spleen / Q000098:blood supply; D013927:Thrombosis / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D016896:Treatment Outcome; D014212:Tretinoin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000677:Amsacrine; D003561:Cytarabine; D014212:Tretinoin; D015255:Idarubicin