Multicenter randomized trial of arsenic trioxide and Realgar-Indigo naturalis formula in pediatric patients with acute promyelocytic leukemia: Interim results of the SCCLG-APL clinical study.

Intravenous arsenic trioxide (ATO) has been adopted as the first-line treatment for acute promyelocytic leukemia (APL). Another arsenic compound named the Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine containing As4 S4 , has been shown to be highly effective in treating adult APL. In the treatment of pediatric APL, the safety and efficacy of RIF remains to be confirmed. This randomized, multicenter, and noninferiority trial was conducted to determine whether intravenous ATO can be substituted by oral RIF in the treatment of pediatric APL. From September 2011 to January 2017, among 92 patients who were 16 years old or younger with newly diagnosed PML-RARa positive APL, 82 met eligible criteria and were randomly assigned to ATO (n = 42) or RIF (n = 40) group. The remaining 10 patients did not fulfilled eligible criteria because five did not accept randomization, four died and one had hemiplegia prior to arsenic randomization due to intracranial hemorrhage or cerebral thrombosis. Induction and consolidation treatment contained ATO or RIF, all-trans-retinoic acid and low intensity chemotherapy. End points included event-free survival (EFS), adverse events and hospital days. After a median 3-year follow-up, the estimated 5-year EFS was 100% in both groups, and adverse events were mild. However, patients in the RIF group had significantly less hospital stay than those in the ATO group. This interim analysis shows that oral RIF is as effective and safe as intravenous ATO for the treatment of pediatric APL, with the advantage of reducing hospital stay. Final trial analysis will reveal mature outcome data.

Improved outcome for Chinese children with acute promyelocytic leukemia: a comparison of two protocols.

OBJECTIVE: Acute promyelocytic leukemia (APL) is now highly curable, except in many developing countries. Introduction of current treatment strategies may improve the outcome for children with APL in these countries. METHODS: The diagnosis was based on the FAB classification and detection of PML-RAR alpha rearrangement. From December 1999 to September 2004, 16 eligible children were treated with an intensive in-house protocol including high-dose AraC and anthracycline. Subsequently, 14 cases were treated with a less intensive protocol modified from the PETHEMA LPA99. RESULTS: The 3.5 years event-free survival (EFS) was 37.5% (95% CI, 13.8-61.2%) for patients treated on initial protocol. The treatment failures were: six patients abandoned treatment (37.5%), two who died of intracranial hemorrhage at diagnosis (6.3%) and sepsis in remission (6.3%) respectively, and two who relapsed (12.5%). Those treated on modified PETHEMA had a 3.5 years EFS of 79.6% (95% CI, 52.9-106.3%). Treatment failures included: one who died of intracranial hemorrhage at diagnosis (7.1%) and one who relapsed (7.1%). The patients on modified PETHEMA had a significantly higher EFS (P = 0.012), lower frequency of sepsis during treatment (7.7% vs. 77.8%; P = 0.0015), and lower hospitalization cost (median US$ 4,700 vs. US$ 20,000; P < 0.0001) than those on in-house protocol. CONCLUSION: Treatment with the less intensive protocol based on the PETHEMA LPA99 study of childhood APL successfully reduced chemotherapy toxicity and lowered hospitalization costs without increasing relapses. This led to decreases in treatment-related morbidity and the treatment abandonment rate, thus improving overall outcome.