Is There Still a Role for Low-Dose All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia in the Arsenic Trioxide Era?

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Abstract

Micro-Abstract

According to pharmacokinetic studies, low and standard doses of all-transretinoic acid (ATRA) have shown similar plasma concentrations. Based on this, as well as on the financial constraints of our uninsured patients, we evaluated the efficacy of low-dose ATRA (LD-ATRA) plus anthracycline-based chemotherapy in 22 newly diagnosed patients with acute promyelocytic leukemia (APL) and concluded that it is safe and effective in achieving complete remission (CR); however, the relapse rate was 27.2%, which is higher than the expected relapse rate using standard doses of ATRA.

Background:

Low-dose all-transretinoic acid (LD-ATRA) has shown similar peak plasma concentrations and a mean area under the concentration time curve in comparison with standard doses of ATRA. We evaluated the efficacy of LD-ATRA plus anthracycline-based chemotherapy in patients with newly diagnosed acute promyelocytic leukemia (APL).

Patients and Methods:

Patients diagnosed with APL during the period of 2002 to 2014 were included. They received ATRA 25 mg/m2 plus anthracycline (doxorubicin or mitoxantrone) as induction chemotherapy, followed by 3 consolidations with LD-ATRA and anthracycline and maintenance therapy with intermittent LD-ATRA and oral chemotherapy for 2 years.

Results:

Twenty-two patients with a median age of 28 years (range, 18–55 years) were included; 17 (77%) were in the low-risk group. Complete remission occurred in 86%, and the early death rate was 9%. At a median follow-up of 32 months (range, 4–126 months) disease-free survival (DFS) was 75% and overall survival (OS) was 86%, with a relapse rate of 27% for the entire follow-up period.

Conclusion:

LD-ATRA plus anthracycline is safe and effective in achieving CR of APL. The early death rate is similar to that of treatment with standard doses, but it appears to be inferior in preventing relapses.

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