Incorporation of arsenic trioxide in induction therapy improves survival of patients with newly diagnosed acute promyelocytic leukaemia

摘要

Objectives: For patients with acute promyelocytic leukaemia (APL), negative reading of a promyelocytic leukaemia/retinoic acid receptor-alpha (PML-RARα) transcript after induction therapy correlates with a good prognosis. However, in the majority of patients given all-trans retinoic acid (ATRA)/anthracycline-based induction therapy, PML-RARα transcript remains even when haematologic complete remission is achieved. To facilitate maximal therapeutic efficacy for patients with APL, this study tested whether the addition of arsenic trioxide (ATO) would increase the rate of molecular complete remission after ATRA/anthracycline-based induction therapy. Methods: Seventy-three patients with APL were induced with a regimen (designated 'AAA') consisting of ATO in combination with ATRA and daunorubicin. After this, a consolidation phase of daunorubicin-based chemotherapy and maintenance therapy with ATRA, ATO and methotrexate was administered. The noted outcomes were rates of complete remission, overall survival and disease-free survival. In addition, PML-RARα transcripts were monitored in 48 patients via RT-PCR. Results: Rates of complete remission, overall survival and 5-yr disease-free survival were 95.89%, 94.52% and 96.28%, respectively. At the preconsolidation checkpoint, 68.75% (33/48) of patients had a negative reading for the PML-RARα fusion transcript. These outcomes were not influenced by mutations in FLT3 (fms-related tyrosine kinase 3) or other prognostic factors. Conclusions: The addition of ATO in the induction regimen was associated with an improved overall outcome for patients with de novo APL, with rather low relapse rate and better long-term survival.