A 3-Year Follow-Up of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (As₂O₃) as Front Line Therapy for Newly Diagnosed Acute Promyelocytic Leukemia (APL).

PURPOSE: To confirm the potential benefit of front-line use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (As2O3) in patients with newly diagnosed acute promyelocytic leukemia (APL) with prolonged follow-up to median of 3-year and compared with historical control.

PATIENTS AND METHODS: Two groups of newly diagnosed patients with APL were included in the analysis. The study group received combination therapy of ATRA and As2O3 includes 56 patients since April 2001. The historical control groups included 56 patients from May 1998 to March 2001. No statistically significant differences of clinical characteristics such as sex, age and hematological data were documented between two groups. For the study group groups, all patients received 25mg/m2 ATRA orally and 0.16mg/kg As2O3 intravenously per day till CR. Once CR achieved, they were given 3 courses of consolidation chemotherapy and then 5 cycles of sequential treatment of ATRA, As2O3 and 6-MP/MTX. For the historical group, the induction therapy was ATRA given at 25mg/m2 daily till CR and chemotherapy was added in case of leukocytosis. The post-remission therapy consists of chemotherapy with ATRA.

RESULT: In study group, 52 (92.9%) patients achieved CR and the time to CR was 26.4±4.5 days. At last follow-up at February 2005, only two patients underwent extramedullary relapse and one died from CNS leukemia while all other patients were alive and remained in hematological remission. With a median follow-up of 34 months (21 to 46 months), the 3-year OS and EFS were estimated as 97.4% and 93.5%. For the historical control groups, the median follow-up was 56 months (12 to 79 months). The 3-year estimated OS and EFS was 83.2% and 57.7% (P=0.069 and 0.00001 respectively). Of notice, in the last follow-up, all evaluable patients in clinical remission maintained a complete molecular response (undetectable PML-RARa via both regular and real-time RT-PCR).

CONCLUSION: Our 3-year follow-up data demonstrate a solid clinical benefit of front-line combination of ATRA and As2O3 in terms of EFS. There was also a trend toward improvement in OS which might translate into better chance of curing the disease.