Introduction

Differentiation syndrome, previously retinoic acid syndrome (RAS) or ATRA syndrome, is a potentially life-threatening complication in patients with acute promyelocytic leukemia (aPML) and associated with all-trans retinoic acid (ATRA) ‘tretinoin’ and arsenic trioxide use.

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Clinical features

Common symptoms:

• Respiratory distress & fever (> 80% cases)
• Pulmonary infiltrates & pulmonary oedema (> 50% cases)
• Weight gain (50% cases)

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Complications

• Pleural effusion → respiratory distress → hypoxia
• Volume overload: Pericardial effusion → hypotension → renal failure

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Management

Best approach for management of RAS is early recognition and prompt administration of steroids at the first sign of unexplained dyspnea, fever, weight gain or pulmonary infiltrates.

• Corticosteroids (Dexamethasone) (10 mg IV BD for ≥ 3 days)
• Cessation of ATRA (depending on severity of RAS)
• Addition of another antineoplastic agent (cytarabine) to ATRA (in patients with high WBC count)
  • Major disadvantage: Bone marrow suppression

Once RAS is resolved, ATRA can be reintroduced.