Francesco Lo Coco, MD, from the University Tor Vergata, Rome, Italy, discusses the use of a chemo-free approach combining arsenic trioxide (ATO) with all-trans retinoic acid (ATRA), which is superior to a conventional approach in the treatment of acute promyelocytic leukemia (APL, APML). He describes how this will now be examined in a randomized study in high-risk APML patients comparing arsenic in combination with all-trans-retinoic acid to chemotherapy. Prof. Lo Coco explains that high-risk APML patients are defined as those with an initial white blood cell count greater than 10 000. The trial aims to demonstrate a benefit in event-free survival (EFS) using the new compound. Prof. Lo Coco points out that APML is now a highly curable disease, and explains that the hope is to come to a new standard particularly avoiding toxicity. He is hopeful that the chemo-free approach can be expanded to high-risk patients, but highlights the challenges of this trial due to the fact that high-risk APML is a rare disease, exhibited by only a quarter of APML patients. Prof. Lo Coco emphasizes the value of collaboration with other European partners in this trial.