[Clinical pharmacology of all-trans retinoic acid (ATRA)]

All-trans-retinoic acid (ATRA, tretinoin) is a natural metabolite of retinol and is normally found in plasma, at concentrations of approximately 0.5-1.5 ng/ml. The in vivo and in vitro studies has demonstrated that in pharmacological doses it can differentiate leukemic cells in acute promyelocytic leukemia (APL). ATRA has been shown to induce complete remission (CR) rates of approximately 90% in newly diagnosed and first relapsing APL. However, CR induced by ATRA alone are usually not sustained and intensive antileukemic consolidation therapy is required to prolong remission. ATRA followed by intensive chemotherapy has improved the outcome of newly diagnosed APL, by increasing the CR rate and by reducing the risk of relapse. The presence of the PML/retinoic acid receptor-alpha (PML/RAR-alpha) fusion gene is a marker for sensitivity to this agent. ATRA therapy is associated with the risk of rapidly rising leukocyte counts, leading to the retinoid acid syndrome which may be fatal if the increase in leukocytes is not reversed. A side effects from these complications ATRA therapy is generally well tolerated.