Acute promyelocytic leukemia (APL) is commonly associated with early deaths and is typically managed by the standard of care of all trans-retinoic acid (ATRA). From clinical experience, the strongest predictors for early deaths are the delayed ATRA administration and hypofibrinogenemia. As such, ATRA plus aggressive correction of hemostatic abnormalities should be given at the earliest suspicion of APL. Notably, oral arsenic trioxide (ATO)/ATRA should not be withheld in the case of high white blood cell (WBC) count or differentiating syndrome. Instead, patients should be managed by aggressive WBC control with hydroxyurea (HU) and prophylactic corticosteroids if differentiation syndrome is suspected.

Currently, Dr. Gill, Harinder Singh Harry noted that certain “international standards” recommended ATRA plus induction chemotherapy with ATRA-based maintenance among high-risk APL patients. At relapse, intravenous ATO-based re-induction can be introduced followed by hematopoietic stem-cell transplantation (HSCT). However, this treatment standard was found to be unfeasible in clinical practice as HSCT should not be the standard therapy for relapsed APL. In a 15-year prospective study, oral ATO-based re-induction alone achieved 79.5% and 67.3% of 5-year and 10-year overall survival (OS), respectively, in patients with first relapse.1 On the other hand, allogeneic HSCT was associated with a therapy-related mortality rate of 17-40% and OS of 46-52%, suggesting that HSCT is an obsolete treatment for relapsed APL.1 Moreover, maintenance ATO/ATRA/ascorbic acid (AAA) was found to have a 5-year and 10-year relapse-free survival (RFS) rates of 89% and 85%, respectively, and OS of 94% and 87%, respectively.² Based on these clinical evidence, Dr. Gill considered HSCT to be unideal for treating APL when compared to the already efficacious ATO/ATRA.

In terms of safety, oral ATO has also demonstrated cardiac benefit in practice with a significantly lower risk of corrected QT prolongation and arrhythmias. As oral ATO can be used in renal impaired patients with arsenic level monitoring, maintenance chemotherapy is no longer recommended and APL patients should be managed by the well-tolerated and out-patient based AAA maintenance therapy.² Invasive or unnecessary procedures, such as the insertion of central venous catheter or the prescription of granulocyte colony-stimulating factor (G-CSF), should also be avoided unless indicated to prevent excessive bleeding.

When managing APL, Dr. Gill reiterated that younger patients should be given ATO/ATRA with daunorubicin on day 1 without delay. Older patients with low WBC at presentation should be given HU to prevent differentiation syndrome with prophylactic corticosteroids if necessary. In practice, the oral ATO-based induction therapy had demonstrated a superior leukemia-free survival (LFS) benefit when compared to placebo and a similar survival benefit when compared to intravenous ATO, suggesting that front-line ATO can be used orally in an out-patient setting. As such, both the consolidation and maintenance therapy for APL should be chemotherapy-free, and Dr. Gill emphasized that, “ATRA plus hemostatic problems correction treatment should be given at the earliest suspicion of APL, and all patients should be referred to front-line oral ATO-based induction therapy without delay.”