title: All-trans retinoic acid therapy for newly diagnosed acute promyelocytic leukemia: comparison with intensive chemotherapy. The Japan Adult Leukemia Study Group (JALSG).
abstract: We analyzed the results of treating patients with newly diagnosed acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) in the JALSG AML-92 study and compared them with those of the AML-87 and AML-89 studies, which consisted of standard chemotherapy. In the AML-92 study, patients were scheduled to receive 45 mg/ m2 oral ATRA daily until achievement of a complete remission (CR). If patients had initial leukocyte counts of > 3.0 x 10(9)/l, they received 40 mg/m2 daunorubicin (DNR) for 3 days and 200 mg/m2 behenoyl cytarabine (BHAC) for 5 days in addition to ATRA. During remission induction therapy, if the patients showed peripheral blood myeloblast and promyelocyte counts of > 1.0 x 10(9)/l, they received additional DNR and BHAC on the same schedule. After achievement of a CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy. Of 196 evaluable patients, 173 (88%) achieved a CR: 59 of 62 (95%) treated with ATRA alone, 41 of 49 (84%) treated with ATRA plus later chemotherapy, 63 of 73 (86%) treated with ATRA plus initial chemotherapy, and 10 of 12 (83%) treated with ATRA plus both initial and later chemotherapy. The CR rate in AML-92 was significantly higher than that in AML-89, but not than that achieved in AML-87. In addition, the early mortality and relapse rates in AML-92 were significantly lower than those in AML-89, but were not than those in AML-87. At a median follow-up of 36 months the predicted 4-year event-free survival (EFS) rate for 196 evaluable patients and the 4-year disease-free survival (DFS) rate for the CR cases were 54% and 62%, respectively. There was a significant difference in DFS between AML-92 and AML-87 (P = 0.0418) but not between AML-92 and AML-89 (P = 0.0687). In contrast, significant differences in EFS between AML-92 and both AML-87 (P = 0.0129) and AML-89 (P = 0.005) were observed. These results suggest that non-cross-resistant therapy combined with ATRA and intensive chemotherapy for APL contributes synergistically to the significant improvement in EFS.
authors.affiliation: Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Asou
authors.forename: K
authors.initials: K
authors.lastname: Adachi
authors.forename: J
authors.initials: J
authors.lastname: Tamura
authors.forename: A
authors.initials: A
authors.lastname: Kanamaru
authors.forename: S
authors.initials: S
authors.lastname: Kageyama
authors.forename: A
authors.initials: A
authors.lastname: Hiraoka
authors.forename: E
authors.initials: E
authors.lastname: Omoto
authors.forename: H
authors.initials: H
authors.lastname: Sakamaki
authors.forename: K
authors.initials: K
authors.lastname: Tsubaki
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: R
authors.initials: R
authors.lastname: Ohno
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007564:Japan; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D016896:Treatment Outcome; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D014212:Tretinoin