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.