Efficacy and safety of consolidation therapy with intermediate and high dose cytarabine in acute myeloid leukemia patients

Figures & data

Table 1. Baseline characteristics of patients (n = 62).

Characteristics	HiDAC (n = 32)	IDAC (n = 30)	P-value
Female, n (%)	20 (62.50)	22 (73.33)	0.522
Age (Year), Median (Range)	38.50 (18–60)	42.50 (20–63)	0.223
ECOG, n (%) 0 1 2 3	4 (12.50) 17 (53.13) 8 (25) 3 (9.38)	2 (6.67) 16 (53.33) 10 (33.33) 2 (6.67)	0.788
Body weight (kg), Median (IQR)	54.50 (47.25, 61.95)	61.15 (52.125, 67.850)	0.084
Height (cm.) (Mean ± SD)	159.78 ± 8.23	159.68 ± 8.24	0.963
Body surface area (kg/m^2) (Mean ± SD)	1.54 ± 0.16	1.61 ± 0.17	0.114
Classification, n (%) AML with Recurrent genetic abnormalities AML with MDS related changes AML, NOS M0 AML, NOS M1/M2 AML, NOS M4 AML, NOS M5 AML, NOS M6 AML, NOS M7	4 (12.50) 2 (6.25) 2 (6.25) 12 (37.50) 7 (21.88) 4 (12.50) 1 (3.13) 0 (0.00)	2 (6.67) 1 (3.33) 0 (0.00) 20 (66.67) 4 (13.33) 1 (3.33) 1 (3.33) 1 (3.33)	0.286
Cytogenetic risk* Favorable Intermediate Adverse	3 (9.38) 21 (65.63) 8 (25.00)	2 (6.67) 19 (63.33) 9 (30.00)	0.863
FLT3-ITD (%) (Only tested patient) Positive	3/7 (42.86)	6/19 (31.58)	0.943
Hb before induction (g/dL) (Mean ± SD)	8.21 ± 1.81	8.24 ± 2.02	0.955
Hct before induction (%) (Mean ± SD)	23.84 ± 6.35	24.41 ± 7.44	0.749
WBC before induction (×10^9/L), Median (IQR)	40,900 (7117.50, 87,132.50)	24,650 (11,707.50, 56,900)	0.751
Peripheral blast before induction (%), Median (IQR)	60.50 (14.25, 79.75)	42.15 (14.75, 80.78)	0.877
Platelet before induction (×10^9/L), Median (IQR)	29,000 (14,800, 67,000)	47,500 (21,750, 66,000)	0.266
LDH before induction (U/L), Median (IQR)	406.50 (284.25, 913.35)	460 (341.00, 636.00)	0.902
BM blast before induction (%), Median (IQR)	80 (61, 90)	80.50 (70, 90)	0.543
Induction cycles, n (%) 1 cycle 2 cycles	26 (81.25) 6 (18.75)	25 (83.33) 5 (16.67)	1.00
Hb before consolidation (g/dL), Median (IQR)	9.60 (8.93, 10.83)	9.25 (8.60, 10.08)	0.447
Hct before consolidation (%), Median (IQR)	29.45 (26.75, 33.70)	28.60 (25.28, 31.98)	0.331
WBC before consolidation (×10^9/L), Median (IQR)	5280 (4110, 7330)	5080 (4075, 6285)	0.617
Peripheral Blast before consolidation (×10^9/L), Median (IQR)	0 (0–0)**	0 (0–0)	0.088
Platelet before consolidation (×10^9/L), Median (IQR)	279,000 (210,250, 338,000)	292,500 (218,500, 408,250)	0.245

Notes: HiDAC: high dose cytarabine; IDAC: intermediate dose cytarabine; SD: standard deviation; IQR: interquartile range; ECOG: Eastern Cooperative Oncology Group performance status; AML: acute myeloid leukemia; AML with MDS related changes: acute myeloid leukemia with myelodysplasia-related changes; AML, NOS M0: acute myeloid leukemia with minimal differentiation; AML, NOS M1/M2: acute myeloid leukemia without/with differentiation; AML, NOS M4: acute myelomonocytic leukemia; AML, NOS M5: acute monoblastic and monocytic leukemia; AML, NOS M6: pure erythroid leukemia, AML, NOS M7: acute megakaryoblastic leukemia; Hb: hemoglobin; Hct hematocrit; WBC: white blood cell; LDH: lactate dehydrogenase (normal 135–225 U/L)

* Favorable risk: t (8:21); Intermediate risk: normal; der (11); der (8), der (21); +4; t (11;18); Unfavorable risk: AML with myelodysplasia-related change; FLT3-ITD mutation; −7; t (6;9); complex chromosome [48,XY,+6,+19,del(11q); 43,XX,−5,−9,−12,−13,−17,+mar1+mar2+mar3; 47,XX,−16,−17,−18,+mar1,+mar2,mar3+mar4]

** Three patients in the HIDAC group had the peripheral blast of 1%, 3.4%, and 4%.

Figure 1. Kaplan–Meier curves of 1-year relapse-free survival of acute myeloid leukemia patients in intermediate-dose cytarabine (IDAC) and high dose cytarabine (HiDAC) groups.

Figure 2. Kaplan–Meier curves according to the 1-year overall survival of acute myeloid leukemia patients in intermediate-dose cytarabine (IDAC) and high dose cytarabine (HiDAC) groups.

Figure 3. Kaplan–Meier curves of 2-year relapse-free survival of acute myeloid leukemia patients in intermediate-dose cytarabine (IDAC) and high dose cytarabine (HiDAC) groups.

Figure 4. Kaplan–Meier curves according to the 2-year overall survival of acute myeloid leukemia patients in intermediate-dose cytarabine (IDAC) and high dose cytarabine (HiDAC) groups.

Figure 5. Comparison of duration of Grades 3–4 thrombocytopenia in each cycle between intermediate dose (IDAC) and high dose cytarabine (HiDAC) consolidation chemotherapy. (P = 0.045); GM: geometric mean.

Table 2. Adverse events in each cycle of high-dose and intermediate-dose cytarabine for consolidation therapy.

Adverse Events	Cycle 1		Cycle 2		Cycle 3		Cycle 4
	HiDAC (%)	IDAC (%)	HiDAC (%)	IDAC (%)	HiDAC (%)	IDAC (%)	HiDAC (%)	IDAC (%)
Anemia
Grade 1	0	0	3.5	4	8	4	0	0
Grade 2	16	10	3.5	0	20	15	25	10
Grade 3	84	87	93	96	72	81	75	90
Grade 4	0	3	0	0	0	0	0	0
Febrile neutropenia
Grade 0	12	6.5	10	18	20	12	0	5
Grade 3	88	87	86	78	80	84	100	90
Grade 4	0	6.5	4	4	0	4	0	0
Grade 5	0	0	0	0	0	0	0	5
Thrombocytopenia
Grade 4	100	100	100	100	100	100	100	100
Bleeding
None	63	63	54	61	76	61	62	74
Minor	34	37	39	39	24	39	38	26
Major	3	0	7	0	0	0	0	0
Nausea and vomiting
Grade 0	75	77	89	93	92	88	88	84
Grade 1	3	6.5	0	0	0	4	12	0
Grade 2	19	10	4	7	8	8	0	11
Grade 3	3	6.5	7	0	0	0	0	5
Diarrhea
Grade 0	88	90	89	93	96	84	86	84
Grade 1	6	7	11	7	0	8	0	16
Grade 2	6	0	0	0	4	8	14	0
Grade 3	0	3	0	0	0	0	0	0
Allergic reaction
Grade 0	75	80	64	75	80	81	63	79
Grade 1	0	3	4	0	0	4	0	5
Grade 2	9	10	11	4	4	4	25	11
Grade 3	16	7	21	21	16	11	12	5
Cardiac Events
Grade 0	94	100	100	100	96	100	100	100
Grade 2	3	0	0	0	0	0	0	0
Grade 3	3	0	0	0	4	0	0	0

Note: HiDAC: high dose cytarabine; IDAC: intermediate-dose cytarabine.