ALL-TRANS-RETINOIC ACID THERAPY FOR NEWLY-DIAGNOSED ACUTE PROMYELOCYTIC LEUKEMIA - COMPARISON WITH INTENSIVE CHEMOTHERAPY

We analyzed the results of treating patients with newly diagnosed acut e 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-9 2 study, patients were scheduled to receive 45 mg/ m(2) oral ATRA dail y until achievement of a complete remission (CR). If patients had init ial leukocyte counts of > 3.0 x 10(9)/l, they received 40 mg/m(2) daun orubicin (DNR) for 3 days and 200mg/m(2) behenoyl cytarabine (BHAC) fo r 5 days in addition to ATRA. During remission induction therapy, if t he patients showed peripheral blood myeloblast and promyelocyte counts of >1.0x10(9)/l, they received additional DNR and BHAC on the same sc hedule. After achievement of a CR, patients received three courses of consolidation and six courses of maintenance/intensification chemother apy. 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 chemother apy, 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 earl y 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 eventfree survival (EFS) rate fo r 196 evaluable patients and the 4-year disease-free survival (DFS) ra te for the CR cases were 54% and 62%, respectively. There was a signif icant 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 diffe rences 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-resista nt therapy combined with ATRA and intensive chemotherapy for APL contr ibutes synergistically to the significant improvement in EFS.