Treatment outcome with chemotherapy in acute promyelocytic leukemia: The Southwest Oncology Group (SWOG) experience

Because of interest in new approaches to treatment of patients with acute promyelocytic leukemia (APL), we analyzed APL treatment outcome in SWOG with chemotherapy from 1982-1991. To evaluate effects of change in nonspecific patient care factors over time we evaluated outcome in two temporal groups (1982-1986, 1986-1991), corresponding to two groups of treatment protocols encompassing all new de novo AML patients entered on acute myeloblastic leukemia (AML) protocols during those years. Surprisingly, APL patients in the 1982-1986 group (n = 45) had much better treatment outcome (complete remission (CR) rate 71%, median overall survival (OS) 106 months, median disease-free survival (DFS) > 105 months) than the later group (n = 96) (CR rate 47%, median OS 13 months, median DFS 26 months) (p = 0.0063, 0.0015, and 0.0001 respectively). All APL patients but two in the 1982-1986 time period were treated on SWOG protocol 8124, which included induction with total daunorubicin (DNR) 210 mg/m² i.v/course, consolidation with two courses with identical dosage of DNR, and intensification at 4 months including another course of identical dosage DNR. We analyzed factors affecting treatment outcome for all patients with APL treated from 1982 to 1991. In multivariate analysis, higher DNR induction dose was significantly associated with CR rate, OS, and DFS (p < 0.001, < 0.0001, and < 0.0001, respectively). Cytosine arabinoside (ARA-C) dose and inclusion of other agents did not correlate significantly with outcome. Because these studies were not randomized for DNR dosage, other factors contributing to outcome cannot be completely excluded, although none were found. Most deaths occurred within 3 months of initiation of therapy on 8124; there were no relapses with higher DNR dosage after 3 years. This excellent outcome should be considered in evaluating newer modalities of therapy such as all-trans retinoic acid (ATRA) for APL. If the high CR induction rate and minimal early deaths with ATRA therapy can be combined successfully with this chemotherapy, most patients with APL may be curable.