Treatment of acute promyelocytic leukemia with single-agent arsenic trioxide

Abstract

It is well recognized that arsenic trioxide (ATO) is an efficacious agent for the treatment of acute promyelocytic leukemia (APL). Use of single agent ATO in the treatment of APL leads to remissions which are durable in the majority. ATO is probably the most effective single agent in the treatment of APL and there have been very few reports of primary resistance. It has been used both as a single agent and in combination with other conventional drugs to treat APL. Use of ATO is the accepted standard of care in the management of relapsed APL, where it is often used effectively as a bridge to a stem cell transplant. However, its role in newly diagnosed APL remains controversial. ATO probably has multiple mechanisms of action. Better understanding of its mechanisms of action/s is likely to lead to more rationale use of this agent or its derivatives either alone or in combination with other drugs. There is limited data on the kinetics of leukemia clearance and normal haematopoietic recovery after the administration of single agent ATO for the treatment of APL, preliminary data suggests that it is likely to be different from conventional therapy. There have been a number of concerns of the potential short and long term toxicity of this agent. Most such concerns arise from the toxicity profile noted in people exposed to long term arsenic exposure in the environment. With the therapeutic doses and schedules of administration of ATO in the treatment of malignancies the overall toxicity profile has been favorable. In a resource constrained environments the use of a single agent ATO based regimen is a realistic and acceptable option to treat almost all patients. In the developed world it has the potential in combination with other agents to improve the clinical outcome with reduction of dose intensity of chemotherapy and remains an option for patients who would not tolerate conventional therapy. In this review we focus on the use of single agent ATO for the treatment of APL and summarize our experience and review the literature.

Figure 1

Five year Kaplan-Meier product limit estimate of disease free survival in the group that had hepatotoxicity, n=23 and those that did not, n=39.

Figure 2

Five year Kaplan-Meier product limit estimate of (A) Overall survival of (n=72) (B) Event free survival (n=72).

Figure 3

Average WBC count among patients with a leucocytic response and who achieved complete remission (n=6), illustrating the triphasic response.

Figure 4

The mean WBC and Platelet count ± 1SE over time among patients treated on single agent ATO regimen. A)WBC response among those with leucocytosis (n=40). B) WBC response among those without leucocytosis (n=18). C) Platelet count recovery (n=60).

Figure 5

Event free survival and cumulative incidence of relapse based on RT-PCR positivity at the end of induction.