Retinoic acid syndrome. Recognition, prevention and management.

The introduction of treatment with tretinoin (all-trans retinoic acid) and its combination with antineoplastic therapy has improved the outcome of acute promyelocytic leukaemia (APL). Retinoic acid syndrome is the major adverse effect of tretinoin and it occurs in about 25% of treated APL patients in the absence of prophylactic measures and is often fatal. Generally, the retinoic acid syndrome is associated with increasing leucocyte counts and is probably caused by the release of several cytokines by maturing blast cells. The retinoic acid syndrome gives a clinical picture of bodyweight gain, respiratory distress, serous effusions and cardiac and renal failure. Adequate prophylaxis, based on the addition to tretinoin of dexamethasone and also, according to most authors, antineoplastic therapy (in case of rapidly increasing leucocyte counts) has decreased the incidence of retinoic acid syndrome to about 15%. Most importantly, these measures have reduced its mortality to about 1% of all treated patients.