Differentiation Syndrome and Coagulation Disorder -- Comparison between
treatment with Oral and Intravenous Arsenics in Pediatric Acute
Background: Realgar-Indigo naturalis formula (RIF) containing A
4S 4 as a major ingredient is an oral
arsenic available in China. The efficacy of RIF on pediatric acute
promyelocytic leukemia (APL) is comparable to arsenic trioxide (ATO).
However, it remains to be explored that the effects of these two
arsenicals on differentiation syndrome (DS) and coagulation disorder
which are the two main life-threatening events in children with APL.
Procedure: We analyzed 68 consecutive children with newly
diagnosed APL involved in SCCLG-APL study (NCT02200978). Patients
received all-trans retinoic acid (ATRA) on day 1 of induction therapy.
ATO (0.16 mg/kg·d) or RIF (135 mg/kg·d) was administrated on day 5 after
mitoxantrone on day 3 (non-high-risk group, NHR) or day 2-4 (high-risk
group, HR). Results: The incidences of DS were 3.0% and 5.7%
in ATO (n = 33) and RIF (n = 35) groups ( p = 0.590), and 10.3%
and 0% in patients with and without differentiation-related
hyperleukocytosis, respectively ( p = 0.04). The dynamic changes
of WBC between the ATO and RIF groups were not statistically different.
However, patients with high WBC counts or percentage of promyelocytes in
peripheral blood tended to develop differentiation-related
hyperleukocytosis. The improvement of coagulation indexes in the ATO and
RIF groups had no statistical difference. Fibrinogen and prothrombin
time had the quickest recovery rate. Conclusions: This study
provides evidences that the incidence of DS and recovery of coagulopathy
are similar whenever treating with RIF or ATO in children with APL.