Optimal treatment strategies for high-risk acute promyelocytic leukemia

Despite major advances in the treatment of acute promyelocytic leukemia (APL), high-risk APL still poses unique challenges. The purpose of this review is to outline current evidence for evaluation and management of high-risk APL and discuss areas of ongoing and future investigation.

With the changing treatment paradigm in APL and increasing use of arsenic trioxide (ATO), reports have questioned the relevance of classic prognostic factors. Despite advancements in therapy, early death remains a primary reason for treatment failure. A randomized, phase III trial demonstrated that all-trans retinoic acid + ATO is at least noninferior and may be superior to all-trans retinoic acid + chemotherapy in low/intermediate-risk APL. One phase III and multiple phase II trials have suggested a benefit of adding ATO to therapy of high-risk patients. Attempts at minimizing chemotherapy in high-risk disease have proven feasible with the use of gemtuzumab ozogamicin, but it is unlikely that cytotoxic chemotherapy will be completely eliminated in this patient population.

Treatment of high-risk APL has evolved significantly over the past 10 years and current scoring systems, management, and treatment regimens have been reviewed. There are as yet unresolved questions, including how to minimize early deaths and optimal therapy in an ATO era.