Maintenance therapy with all-trans retinoic acid and arsenic trioxide improves relapse-free survival in adults with low- to intermediate-risk acute promyelocytic leukemia who have achieved complete remission after consolidation therapy

Figures & data

Figure 1 Treatment schedule of APL patients classified as low- to intermediate-risk category.

Abbreviations: 6-MP, 6-mercaptopurine; APL, acute promyelocytic leukemia; As₂O₃, arsenic trioxide; ATRA, all-trans retinoic acid; CR, complete remission; IDA, idarubicin; IV, intravenous; Mitox, mitoxantrone; MTX, methotrexate; PO, per oral.

Table 1 Clinicopathologic characteristics of 58 patients with APL receiving different maintenance regimens

Characteristic	ATRA+As2O3 maintenance (N=30)	ATRA+chemotherapy maintenance (N=28)	P-value
Age (years), median (range)	41 (15–64)	43.5 (17–70)	0.4933
15–39, n (%)	12 (40.0)	12 (42.9)	0.557
40–60, n (%)	16 (53.3)	12 (42.9)
>60, n (%)	2 (6.7)	4 (14.2)
Sex
Male, n (%)	12 (40.0)	19 (67.9)	0.034
Female, n (%)	18 (60.0)	9 (32.1)
WBC count (×10^9/L), median (range)	1.49 (0.52–6.83)	2.14 (0.85–8.7)	0.0165
<5, n (%)	28 (93.3)	20 (71.4)	0.027
5–10, n (%)	2 (6.7)	8 (28.6)
Platelet count, ×10^9/L, median (range)	20.5 (2–176)	28.5 (3–135)	0.4884
≤40, n (%)	24 (80.0)	17 (60.7)	0.107
>40, n (%)	6 (20.0)	11 (39.3)
Hemoglobin (g/L), median (range)	81 (39–144)	90.5 (44–149)	0.1435
Induction regimens
ATRA+As2O3+IDA, n (%)	8 (26.7)	3 (10.7)	0.121
ATRA+IDA, n (%)	22 (73.3)	25 (89.3)

Abbreviations: APL, acute promyelocytic leukemia; As₂O₃, arsenic trioxide; ATRA, all-trans retinoic acid; IDA, idarubicin; WBC, white blood cell.

Table 2 Adverse events during maintenance therapy

Adverse events	ATRA+As2O3 maintenance (N=30)	ATRA+chemotherapy maintenance (N=28)	P-value
Neutropenia (grade 3–4)	0	9	0.001
Liver function derangement	3	4	0.701
QT prolongation	2	0	0.492
Dyspepsia	1	3	0.344
Herpes zoster reactivation	0	1	0.483
Hemolysis	1	0	1.000

Abbreviations: ATRA, all-trans retinoic acid; As₂O₃, arsenic trioxide.

Table 3 Impacts of clinicopathologic features on relapse in 58 APL patients during maintenance therapy

Clinicopathologic parameters	Outcome		P-value
	Remission	Relapse
Sex			0.432
Male	26	5
Female	25	2
Age (years)			1.000
≤40	25	3
>40	26	4
WBC count (×10^9/L)			0.592
≤5	43	5
>5	8	2
Platelet count (×10^9/L)			0.661
≤40	35	6
>40	16	1
Hemoglobin (g/L)			0.083
<100	39	3
≥100	12	4
Induction regimens			0.327
ATRA+As2O3+IDA	11	0
ATRA+IDA	40	7
Maintenance regimens			0.004
ATRA+As2O3	30	0
ATRA+chemotherapy	21	7

Abbreviations: APL, acute promyelocytic leukemia; As₂O₃, arsenic trioxide; ATRA, all-trans retinoic acid; IDA, idarubicin; WBC, white blood cell.

Figure 2 Relapse-free survival according to the type of maintenance regimen. Relapse-free survival is estimated from the completion of consolidation.

Abbreviations: As₂O₃, arsenic trioxide; ATRA, all-trans retinoic acid.

Table 4 Impacts of clinicopathologic parameters on RFS in 58 APL patients during maintenance therapy

Clinicopathologic parameters	3-year RFS	P-value (log-rank)
Sex		0.4376
Male	0.8640
Female	0.9630
Age (years)		0.8146
≤40	0.8889
>40	0.9305
WBC count (×10^9/L)		0.6536
≤5	0.9128
>5	0.9000
Platelet count (×10^9/L)		0.3020
≤40	0.8733
>40	1.0000
Hemoglobin (g/L)		0.0895
<100	0.9491
≥100	0.8125
Induction regimens		0.2724
ATRA+As2O3+IDA	1.0000
ATRA+IDA	0.8908
Maintenance regimens		0.0159
ATRA+As2O3	1.0000
ATRA+chemotherapy	0.8182

Abbreviations: APL, acute promyelocytic leukemia; As₂O₃, arsenic trioxide; ATRA, all-trans retinoic acid; IDA, idarubicin; RFS, relapse-free survival; WBC, white blood cell.

Table 5 Impacts of clinicopathologic features on relapse during maintenance therapy in 47 APL patients receiving ATRA+IDA as an induction regimen

Clinicopathologic parameters	Outcome		P-value
	Remission	Relapse
Sex			0.295
Male	20	5
Female	20	2
Age (years)			0.727
≤40	20	3
>40	20	4
WBC count (×10^9/L)			0.492
≤5	33	5
>5	7	2
Platelet count (×10^9/L)			0.331
≤40	27	6
>40	13	1
Hemoglobin (g/L)			0.086
<100	30	3
≥100	10	4
Maintenance regimens			0.007
ATRA+As2O3	22	0
ATRA+chemotherapy	18	7

Abbreviations: APL, acute promyelocytic leukemia; As₂O₃, arsenic trioxide; ATRA, all-trans retinoic acid; IDA, idarubicin; WBC, white blood cell.

Table 6 Impacts of clinicopathologic parameters on RFS during maintenance therapy in 47 APL patients receiving ATRA+IDA as an induction regimen

Clinicopathologic parameters	3-year RFS	P-value (log-rank)
Sex		0.4381
Male	0.8337
Female	0.9545
Age (years)		0.7301
≤40	0.8696
>40	0.9079
WBC count (×10^9/L)		0.7274
≤5	0.8904
>5	0.8889
Platelet count (×10^9/L)		0.2928
≤40	0.8436
>40	1.0000
Hemoglobin (g/L)		0.1158
<100	0.9351
≥100	0.7857
Maintenance regimens		0.0264
ATRA+As2O3	1.0000
ATRA+chemotherapy	0.7958

Abbreviations: APL, acute promyelocytic leukemia; As₂O₃, arsenic trioxide; ATRA, all-trans retinoic acid; IDA, idarubicin; RFS, relapse-free survival; WBC, white blood cell.