Abstract
PURPOSE: To determine the efficacy of front-line use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (As2O3) in patients with newly diagnosed acute promyelocytic leukemia (APL).
PATIENTS AND METHODS: Since 2001, 61 patients have received ATRA (25mg/m2) and As2O3 (0.16mg/kg) daily till CR and all patients received 3 consolidation chemotherapy and then received 5 cycles of sequential treatment of ATRA, As2O3 and 6-MP/MTX. The efficacy of treatment protocol in induction remission, molecular response and relapse-free survival were compared with our historical control.
RESULT: 58 (95.1%) patients achieved CR and all remain relapse free with the current protocol. Though ATRA/As2O3 duet did not improve the hematological/molecular remission rate and reduced the early mortality after induction, it did induce an early hematological response (26.1±4.1 days). During limited follow-up (20 to 39 months), both RFS and OS are significantly increased in patients who received the ATRA/As2O3/chemotherapy triad as post-remission therapy compared to the historical control. PML-RARa mRNA was retrospectively assessed by quantitative real-time reverse transcription-polymerase chain reaction (RQ-RT-PCR) before treatment, after CR, after consolidation and during follow-up period in 36 patients with ATRA and As2O3 combination treatment. PML-RARa normalized dose was found to be more significantly decreased after remission induction (median fold reduction: 335.8), and after consolidation (median fold reduction: 358362.2), as compared with ATRA or As2O3 mono-therapy. The addition of As2O3 into post-remission therapy can further increase the post-remission molecular response through either qualitative or quantitative RT-PCR measurement.
CONCLUSION: Our current follow-up data suggested a potential benefit of front-line combination of ATRA and As2O3, which might translate into better chance of curing the disease.
Author notes
Corresponding author
