Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

“…In the updated results of the German-Italian trial of ATRA plus arsenic trioxide (n 5 122) versus AIDA (n 5 132), the CR rates were 100% versus 97% (p 5 0.12), the 2-year event-free survival rates 98% versus 85% (p 5 0.0002), the relapse rates 1.1% versus 9.4% (p 5 0.005), and the estimated 4-year survival rates 99% versus 94% (p 5 0.01) [9]. The Medical Research Council (MRC) also confirmed the noninferiority of ATRA plus arsenic trioxide compared with AIDA across APL categories [10].…”

“…In the MD Anderson studies, the use of fludarabine with high-dose cytarabine and GO (or idarubicin) during induction and consolidations, the application of 4-6 consolidation courses, and modifying therapy for persistent MRD resulted in cure rates of 80% in both inversion 16 and t(8;21) AML (Fig. 3) [10][11][12]. The MRC trials using the fludarabine, high-dose cytarabine, and idarubicin combination (FLAG-Ida regimen) have reported estimated cure rates of 80-90% in CBF AML [14,15].…”

Therapy-related myelodysplastic syndrome after successful treatment of acute promyelocytic leukemia: case report and literature review

“…These papers do not support the potential correlation between dose-intensity of topoisomerase II inhibitors and a higher prevalence of t-MNs in low risk patients who are generally treated with lower dose anthracycline regimens. The transition toward chemotherapyfree first-line treatment based on the association of ATRA + ATO in newly diagnosed low and intermediary risk cases comes as a solution in trying to lower the incidence of t-MNs [16,18].…”

“…The analysis of the AIDA study has shown an increase in the 6-year overall survival (OS) of 87.4% and a disease free survival (DFS) of 85.6% and cumulative incidence of relapse (CIR) 10.7% [14]. An analysis of an ATRA + ATO trial set between 2013 and 2016 has shown a 30,5-36 months OS of 93%-99,1%, event-free survival (EFS) 91%-98%, cumulative incidence of relapse (CIR) 1-1,1% [16,17,18]. The shift to first-line therapy of ATRA + ATO (chemotherapy free) still poses ATO related problems: dose calculation, induction and consolidation regimens, the cost of the drug, long term toxicity (neurologic effects, liver damage), ease of administration (advantages of a drug that may be administered orally as opposed to intravenously).…”

The role of targeted therapy in the management of patients with AML

“…Relapse of APL after frontline ATRA 1 arsenic trioxide 1 GO has been exceedingly unusual (4%) with long-term follow-up, including patients with presenting white blood cell count of .10 3 10 9 /L. 67,68 Summarizing all the available phase 3 data from 5 phase 3 trials in adults, a UK National Cancer Research Instiute meta-analysis studied 3325 patients treated in these studies. 69 The metaanalysis showed a statistically significant reduction in relapse rates and improved OS for GO-treated patients across these trials, without appreciable increases in toxicity.…”