Arsenates in the Treatment of Hematological Malignancies

Arsenic trioxide (As2O3) for leukemia treatment has been known for over a century. The recent rekindling of the interest in As2O3 is due to its high efficacy in acute promyelocytic leukemia (APL), inducing remissions in over 90% of newly diagnosed or relapsed cases. Most As2O3 preparations are intravenous, although an oral formulation is similarly efficacious. Important side effects include prolongation of QT interval, leucocytosis and the APL differentiation syndrome. Combined use of As2O3 and all trans-retinoic acid (ATRA) has been found to be useful in APL relapsing from previous arsenic-induced remissions. Furthermore, As2O3 + ATRA may give remissions of better quality in newly diagnosed APL. Current research centers on the early introduction of As2O3 in the overall treatment plan of APL, including its use in maintenance therapy after first complete remission. As2O3 has also been used in other hematological malignancies. Of particular promise is the use of As2O3 in multiple myeloma.