Low-dose hypomethylating agent decitabine in combination with aclacinomycin and cytarabine achieves a better outcome than standard FLAG chemotherapy in refractory/relapsed acute myeloid leukemia patients with poor-risk cytogenetics and mutations

Figures & data

Table 1 Characterization of patients with RR-AML in FLAG and DAC groups

Characteristics	Overall	FLAG		DAC
		Number of patients	%	Number of patients	%
Patients	35	18	51.4	17	48.6
Classification
Refractory	23	12	83.3	11	64.7
Relapsed	12	6	16.7	6	35.3
Age (years)
<20	15	8	44.4	7	41.2
20–39	8	5	27.8	3	17.6
40–60	8	4	22.2	4	23.5
>60	4	1	5.6	3	17.6
Gender
Male	20	10	55.6	10	58.8
Female	15	8	44.4	7	41.2
Initial WBC count (×10^9)
<4	9	6	33.3	3	17.6
4–10	7	3	16.7	4	23.5
>10	19	9	50.0	10	58.8
Initial cytogenetics
Normal	14	8	44.4	6	35.3
Abnomal	21	10	55.6	11	64.7
Fusion genes
AML1/ETO	5	4	22.2	1	5.9
CBFB-MYH11	2			2	11.8
ETO	4	2	11.1	2	11.8
EVI1	1			1	5.9
HOX11	2	1	5.6	1	5.9
P210	3	2	11.1	1	5.9
PML-Rara	1			1	5.9
MLL-AF9	1	1	5.6
Mutation
WT1	33	17	94.4	16	94.1
FLT3	20	10	55.6	10	58.8
NPM1	13	5	27.8	8	47.1
Subtypes
M1	1	1	5.6
M2	22	13	72.2	9	52.9
M3	1			1	5.9
M4	4	1	5.6	3	17.6
M5	4	3	16.7	1	5.9
Unknown	3			3	17.6
Hepatolienal characteristics
Hepatomegaly	2	1	5.6	1	5.9
Splenomegaly	13	5	27.8	8	47.1
Hepatosplenomegaly	5	2	11.1	3	17.6
Others	15	10	55.6	5	29.4
Frontline therapy
HAD	32	18	100	14	82.4
DA	10	2	11.1	8	47.1
MA	14	7	38.9	7	41.2
IA	10	5	27.8	5	29.4
CAG	3	1	5.6	2	11.8
ATO	1			1	5.9
FA	1			1	5.9
Remission duration after frontline therapy
<3 months	6	4	22.2	2	11.8
3–6 months	5	1	5.6	4	23.5
>6 months	1	1	5.6
Therapeutic response
CR	17	6	33.3	11	64.8
PR	10	4	22.2	6	35.3
NR	8	8	44.4	0	0
Consolidated therapy
Chemotherapy
HAD	4	2	11.1	2	11.8
CAG	1	1	5.6
IA	5	1	5.6	4	23.5
DA	2			2	11.8
MA	2			2	11.8
MAE	1			1	5.9
alloSCT
In remission	9	6	33.3	3	17.6
Outside remission	2	2	11.1
Treatment-related mortality	1	1	5.6

Abbreviations: ATO, arsenic trioxide; CAG, low-dose cytarabine, aclarubicin and G-CSF; CR, complete remission; DA, daunorubicin and cytarabine; DAC, low-dose decitabine with aclacinomycin and cytarabine; FA, fludarabine and cytarabine; FLAG, fludarabine in combination with cytarabine and G-CSF; HAD, homoharringtonine, cytarabine and daunorubicin; IA, idarubicin and cytarabine; MA, mitoxantrone and cytarabine; MAE, mitoxantrone, cytarabine and etoposide; NR, no response; PR, partial response; RR-AML, relapsed/refractory acute myeloid leukemia; SCT, stem cell transplantation; WBC, white blood cell count.

Table 2 Response of RR-AML patients with FLAG and DAC treatment

Response	FLAG group (n=18)	DAC group (n=17)	Total (n=35)	P-value
NR (%)	8 (44.4)	0 (0)	8 (22.8)	–
OR (%)	10 (55.6)	17 (100)	27 (77.1)	0.002
CR (%)	6 (33.3)	11 (64.7)	17 (48.6)	0.002

Abbreviations: CR, complete response; DAC, low-dose decitabine with aclacinomycin and cytarabine; FLAG, fludarabine in combination with cytarabine and G-CSF; NR, no response; OR, overall response; RR-AML, relapsed/refractory acute myeloid leukemia.

Figure 1 Kaplan–Meier plot of OS for FLAG and DAC regimen groups.

Notes: The blue line represents the FLAG group; the green line represents the DAC group.
Abbreviations: DAC, low-dose decitabine with aclacinomycin and cytarabine; FLAG, fludarabine in combination with cytarabine and G-CSF; OS, overall survival.

Table 3 FLAG and DAC treatment response in RR-AML patients who had poor-risk cytogenetics and mutation status

Response	Mutations	FLAG group	DAC group	Total	P-value
NR (%)	Poor-risk cytogenetics	4 (57.1)	0 (0)	4	–
	WT1	8 (47.1)	0 (0)	8	–
	FLT-3	4 (40.0)	0 (0)	4	–
	NPM1	3 (60.0)	0 (0)	3	–
OR (%)	Poor-risk cytogenetics	3 (42.9)	7 (100)	10	0.018
	WT1	9 (52.9)	16 (100)	25	0.002
	FLT-3	6 (60.0)	10 (100)	16	0.025
	NPM1	2 (40.0)	8 (100)	10	0.013
CR (%)	Poor-risk cytogenetics	1 (14.3)	4 (57.1)	5	0.040
	WT1	6 (35.3)	11 (68.8)	17	0.002
	FLT-3	3 (30.0)	5 (50.0)	8	0.038
	NPM1	2 (40.0)	4 (50.0)	6	0.058

Abbreviations: CR, complete response; DAC, low-dose decitabine with aclacinomycin and cytarabine; FLAG, fludarabine in combination with cytarabine and G-CSF; NR, no response; OR, overall response; RR-AML, relapsed/refractory acute myeloid leukemia.