Retinoic acid syndrome

Retinoic acid syndrome (RAS) is a potentially life-threatening complication observed in patients with acute promyelocytic leukemia (APML) and first thought to be specifically associated with all-trans retinoic acid (ATRA) (also known as tretinoin) treatment.^[1] Subsequently it was recognized that so-called RAS appeared in APML patients who had been treated with another highly efficacious drug, arsenic trioxide, and yet did not appear in patients treated with tretinoin for other disorders. These facts and others support the notion that RAS depends on the presence of the malignant promyelocytes. This has led to the growing deprecation of the term ‘retinoic acid syndrome’ and to an increasing use of the term differentiation syndrome to signify this APML treatment complication.^[2]

Several mechanisms have been speculated including a capillary leak syndrome from cytokine release from the differentiating myeloid cells. Mediation by cathepsin G has also been suggested.^[3]

The etiology of RAS remains unclear. Alternatively, all-trans retinoic acid (ATRA) and arsenic trioxide may cause the maturing myeloid cells to acquire the ability to infiltrate organs such as the lung.

The syndrome is characterized by dyspnea, fever, weight gain, hypotension, and pulmonary infiltrates.

An elevated white count is sometimes associated with this syndrome, but is not a prerequisite.

The treatment of RAS usually involves administering dexamethasone IV, with the dosage usually 10 mg BID for ten days. It is important for patients to discontinue the use of tretinoin due to the elevation of WBC and possible low blood oxygen.

Once RAS has resolved, pro-differentiation chemotherapy can be resumed.