INTRODUCTION
The long-term survival rate of acute promyelocytic Leukemia (APL) is exceeding 90% with contemporary treatment combining arsenic compounds, all-transretinoic acid (ATRA) and anthracycline-based chemotherapy (CHT).1-4 However, early death (ED) is still a major issue in APL. The two main causes of ED are hemorrhage and differentiation syndrome (DS). The rate of early hemorrhagic death remains at about 5-10% in the clinical trial setting.5 DS develops in up to 19% of the patients and DS-related death rate can be as high as 5.7%.5Therefore, reducing the incidences of DS and hemorrhage is critical for further increasing the survival in patients with APL.
There are two arsenic compounds available for the treatment of APL in China: arsenic trioxide (ATO) and Realgar-Indigo naturalis formula (RIF). RIF is a traditional Chinese medicine containing realgar (As4S4) as well as Indigo naturalis, Radix salviae miltiorrhizae and Radix pseudostellariae which yield synergy anti-leukemia effects.6 RIF has been proven as effective as ATO in treating childhood and adult APL, with the advantage of being an oral drug and reducing hospital stay.1, 2
The impact of RIF and ATO on the early complications may be different. In adult patients, RIF and ATO have similar effects on the recovery of coagulopathy, 7 but not on the kinetics of white blood cell count (WBC) ,8 and RIF group has a higher peak WBC compared to ATO group during induction treatment.8Leukocytosis is an important factor in the development of DS. It is known that there are important distinctions between pediatric and adult patients with APL.9 In fact, 84%-100% of pediatric patients with non-high risk (NHR) APL on ATO and ATRA induction therapy developed leukocytosis (WBC > 10 × 109/L) and is much higher than 35%-47% in adult counterpart on the similar therapy.10-15 To our knowledge, there is no report comparing the impacts of RIF and ATO on DS and hemorrhage in pediatric patients with APL. Therefore, the present study analyses these two main life-threatening events in pediatric patients with APL on induction therapy with SCCLG-APL (South China Children Leukemia Group-APL) protocol containing ATO or RIF, ATRA and mitoxantrone.