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 patents 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]
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The syndrome is characterized by dyspnea, fever, weight gain, hypotension, and pulmonary infiltrates. This is effectively treated by giving dexamethasone and holding ATRA (or arsenic trioxide) in severe cases. An elevated white count is sometimes associated with this syndrome, but is not a prerequisite.
Once RAS has resolved, pro-differentiation chemotherapy can be ali resumed.
The etiology of RAS is not clear cut. Several causes have been speculated including a capillary leak syndrome from cytokine release from the differentiating myeloid cells. Alternatively, ATRA may cause the maturing myeloid cells to acquire the ability to infiltrate organs such as the lung.
Mediation by cathepsin G has been suggested.[3]