Oral Arsenic and Retinoic Acid for Children with Non High-Risk Acute Promyelocytic Leukemia

Objective

Acute promyelocytic leukemia (APL) has now become a highly curable disease with the all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as first-line treatment. Adult non high-risk APL patients (WBC< 10×10⁹/L) can be cured using only ATRA and ATO without chemotherapy. We also provided similar results using a totally oral (oral arsenic and ATRA), chemo-free outpatient protocol (Beijing protocol) for adult patients with non high-risk APL. However, experiences in children with APL are scarce. These prompted us to try to extend the Beijing protocol to children patients with non high-risk APL.

Methods

We conducted a single-centre pilot study to evaluate the efficacy of oral arsenic and ATRA for children patients with non high-risk APL from April 2014 through October 2016. Nine patients with the median age of 16 years old (range 13-18) were enrolled and received oral arsenic realgar-indigo naturalis formula (RIF, 60 mg/kg) and ATRA (25 mg/m²) as induction therapy until hematologic complete remission (CR). Hydroxyurea and/or cytarabine (without anthracyclines) were used to diminish the increased WBC during induction treatment. The post-remission therapy included RIF in a 4-week on and 4-week off , and ATRA in a 2-week on and 2-week off schedule for 7 months. The primary endpoint was the complete molecular response (CMR) post-consolidation, defined as absence of detectable PML-RARA transcripts by quantitative PCR. Secondary endpoints included CR, safety, hospital stay. Median follow-up was 15 months (range 6-36 months) by April 2017.

Results

All 9 patients achieved hematologic CR after a median time of 30 days. CMR rate was 100% at 3 and 6 months. Grade1,2,3, and 4 liver adverse events was 2,3,1,0, respectively. Differentiation syndrome occurred in 3 patients during induction (Table1). No hematological relapse or molecular relapse occurred at the last follow-up. Both the 2-year estimated EFS and OS were 100%.The total hospital time was 17 days (4-37 days) during the treatment phase. Of note, 100% (9/9) of patients completed the post-remission therapy on an outpatient basis without hospitalization. Patients resumed their usual lifestyle during post-remission therapy and their QoL was nearly normal during post-remission therapy.

Conclusions

Our study, which employed a largely home-based treatment protocol with complete oral regimen, chemo-free during induction in children patients with non high-risk APL, suggested to be effective, convenient. However, lager sample studies and long-term outcome are warranted.