title: All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results.
abstract: Twenty-two patients with acute promyelocytic leukemia were treated with all-trans retinoic acid (RA, 45 mg/m2 per day) for 90 days. Of the 22, four patients were previously untreated, two were resistant after conventional chemotherapy, and 16 were in first (n = 11), second (n = 4), or third (n = 1) relapse. We observed 14 complete response, four transient responses, one failure, and three early deaths. Length of hospitalization and number of transfusions were notably reduced in complete responders. Correction of coagulation disorders and an increase of WBCs were the first signs of all-trans RA efficacy. Morphologic analysis performed at days 0, 15, 30, 45, 60, and 90 showed that complete remissions were obtained without bone marrow (BM) hypoplasia. Presence of Auer rods in the maturing cells confirmed the differentiation effect of the treatment. At remission, the t(15;17) initially present in 20 patients was not found. The in vitro studies showed a differentiation in the presence of all-trans RA in 16 of the 18 tested cases. The single nonresponder to all trans RA in vitro did not respond in vivo. Adverse effects of RA therapy--skin and mucosa dryness, hypertriglyceridemia, and increase of hepatic transaminases--were frequently noted. We also observed bone pain in 11 patients and hyperleukocytosis in four patients. Whether maintenance treatment consisted of low-dose chemotherapy or all-trans RA, early relapses were observed. Five patients are still in complete remission (CR) at 4 to 13 months. Our study confirms the major efficacy of all-trans RA in M3, even in relapsing patients. Remissions are obtained by a differentiation process.
authors.affiliation: Département d'Hématologie, Hôpital St Louis, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Castaigne
authors.forename: C
authors.initials: C
authors.lastname: Chomienne
authors.forename: M T
authors.initials: MT
authors.lastname: Daniel
authors.forename: P
authors.initials: P
authors.lastname: Ballerini
authors.forename: R
authors.initials: R
authors.lastname: Berger
authors.forename: P
authors.initials: P
authors.lastname: Fenaux
authors.forename: L
authors.initials: L
authors.lastname: Degos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D014212:Tretinoin