What are the considerations for the pharmacotherapeutic management of acute promyelocytic leukemia in children?

Figures & data

Figure 1. Mechanism of action of ATRA/ATO combination.

APL characteristic differentiation block at promyelocytic stage is due to the translocation t(15;17)(q24.1;q21.1) . The synergistic action of ATRA/ATO reactivates the granulocytic differentiation through proteasomal degradation of the PML-RARA fusion oncoprotein. PML, promyelocytic leukemia protein; RARA, retinoic acid receptor-a; ATRA: all-trans retinoic acid; ATO: arsenic trioxide.

Table 1. Studies reporting ATRA/ATO combinations for induction and consolidation in children with newly diagnosed APL

Patients, n	APL type	ATRA dose (mg/m^2)	ATO dose (mg/kg^2)	Chemotherapy used	Median follow-up time, months	DFS, %	OS, %	Ref
43	NR*	20–40	0.16	yes	75	97	95	8
11	11 SR	25	0.15	yes	29	100	100	9
18	16 SR/2 HR	25	0.15	no	24	100	100	10
21	19 SR/3 HR	25	0.15	yes	17	100	100	11
17	11 SR/6 HR	25	0.16	no	36	100	94	12
193	125 SR/68 HR^&	25	0.15^	yes	29	97(SR)/90(HR)	99(SR)/95(HR)	13

*43 consecutive patients treated with ATRA/ATO combination only in induction.

^ This study included also the use of oral ATO (RIF) at a dose of 60 mg/kg daily in two or three divided doses.

& reported as Sanz-risk criteria; in this study instead patients were classified differently according to white blood cell counts and presence of FLT3 mutation (see text).

NR: not reported; APL: acute promyelocytic leukemia, ATRA: all-trans retinoic acid; ATO: arsenic trioxide; DFS: disease-free survival (when absent was used event-free survival); OS: overall survival; SR: standard-risk; HR: high-risk.