A 32-year-old man presents with fever, bleeding gums, and petechiae. Bone marrow examination reveals 85% blasts with Auer rods and cytoplasmic granules. Flow cytometry confirms AML with t(15;17). What is the drug of choice for induction therapy in this patient?
A. Daunorubicin + cytarabine
B. Idarubicin + high-dose cytarabine
C. All-trans retinoic acid (ATRA) + arsenic trioxide
APL with t(15;17) is a medical emergency with unique treatment paradigm distinct from other AML subtypes.
Molecular Basis
The t(15;17) translocation produces the PML-RARA fusion gene, which encodes an aberrant retinoic acid receptor. This fusion protein blocks differentiation and causes severe coagulopathy (DIC).
First-Line Induction Regimen
Table
Component
Role
Mechanism
ATRA
Differentiating agent
Binds fusion protein, restores normal transcription, forces maturation
Arsenic trioxide (ATO)
Synergistic cytotoxic
Degrades PML-RARA fusion protein via proteasomal pathway
High-YieldNEET PG
The combination of ATRA + ATO achieves 90–95% complete remission with cure rates >80% in newly diagnosed APL — superior to traditional anthracycline-based chemotherapy.
Clinical Pearl
ATRA monotherapy causes ATRA syndrome (fever, respiratory distress, weight gain, pulmonary infiltrates) in 5–30% of patients → managed with dexamethasone prophylaxis or early intervention.
ATO is added to reduce ATRA syndrome risk and improve overall survival.
Early recognition of t(15;17) is critical: initiate ATRA + ATO before cytogenetics confirm, given the high mortality from DIC if delayed.
