High Risk Acute Promyelocytic Leukemia - An Enigma for Hematologists: Optimizing Treatment with APML-4 Protocol

Management of Acute Promyelocytic Leukemia (APML) has improved drastically after the introduction of ATRA (All-trans-retinoic acid) and Arsenic trioxide (ATO). The use of APML-4 protocol has shown its effectiveness in Australian population. We know that high-risk APML represents a subset with poor outcomes. There is scarcity of literature reporting outcomes of high-risk APML from India. We present a 5-year retrospective analysis of the safety and efficacy of APML-4 protocol in our 28 high-risk patients. Of 28 patients, there were 8(28.5%) early deaths; all 20 patients (100%) who were alive achieved hematologic complete remission post-induction and molecular complete remission post-consolidation. The 5-year disease free survival, failure free survival (FFS) and overall survival were 100%, 69% and 69% respectively. Factors affecting FFS were age > 45 years (p = 0.008), baseline ECOG-PS > 1 (p < 0.0001), and grade 3-4 differentiation syndrome (p = 0.008). APML-4 protocol in high-risk patients is capable of achieving excellent disease control with less toxicities. While early induction deaths in high-risk APML still remain an issue, protocol modifications (for steroid and anthracyclines) are important considering high frequency of infections at baseline and during induction therapy in our population.