Patients’ characteristics
The data of 231 MDS patients including 95 females and 136 males were collected over a 10-year period with a median age of 61 years (range 16-90 years). Among these MDS patients, the median OS was 27 months (range 0-125 months, 95% CI 15.96-38.04 months) and 26 patients (11.3%) progressed to AML. Basing on the 2016 WHO classification, all patients were classified as MDS as follows: 23(10.0%) MDS-SLD, 65(28.1%) MDS-MLD, 17(7.4%) MDS-RS, 61(26.4%) MDS-EB1, 50(21.6%) MDS-EB2, 1(0.4%) MDS-del(5q) including del(5q) alone or with 1 additional abnormality except -7 or del(7q), 14 (6.1%) MDS-U. Besides, 196 patients were stratified into IPSS-R risk groups as follows: 13 (6.6%) very low, 38(19.4%) low, 67(34.2%) intermediate, 42(21.4%) high and 36(18.4%) as very high. Of these, the median IPSS-R score was 4.5(1.0-10.0). Further information was provided in Table1.
Table 1
Comparison between MDS with low ApoA1 group and high ApoA1 group in 231 MDS patients
Variable
|
All patients
|
Low ApoA1 group
(n=126)
|
High ApoA1 group
(n=105)
|
statistics
|
P value
|
Gender(n)
|
231
|
|
|
χ2=10.072
|
0.002
|
Male/Female, n
|
136/95
|
86/40
|
50/55
|
|
|
Age [years, median(quartile)]
|
62(51,73)
|
63(28~86)
|
61 (16~90)
|
Z =-1.842
|
0.065
|
BM Blast[%,median(quartile)]
|
4.5(1,9)
|
6(0~19.5)
|
3(0~19)
|
Z =-2.666
|
0.008
|
Peripheral Blood
|
|
|
|
|
|
NE [×109/L, median(quartile)]
|
1.2(0.7,2.1)
|
1.1(0~7.4)
|
1.3(1.1~6.9)
|
Z =-1.221
|
0.093
|
HB [g/L, median(quartile)]
|
75(62,99)
|
67(22~142)
|
88(50~142)
|
Z =-5.487
|
<0.001
|
PLT [×109/L,median(quartile)]
|
52(28,96)
|
46(4~332)
|
61(2~434)
|
Z =-3.062
|
0.002
|
ApoA1[g/L,median(quartile)]
|
1.0(0.82,1.18)
|
0.84(0.34~1.02)
|
1.19(1.03~2.36)
|
Z =-13.081
|
<0.001
|
2016WHO classification
|
|
|
|
χ2=14.575
|
0.042
|
MDS-SLD, % (n/n)
|
10.0% (23/231)
|
5.6% (7/126)
|
15.2% (16/105)
|
|
|
MDS-MLD, % (n/n)
|
28.1% (65/231)
|
26.2% (33/126)
|
30.5% (32/105)
|
|
|
MDS-RS-SLD, % (n/n)
|
2.6% (6/231)
|
2.4% (3/126)
|
2.9% (3/105)
|
|
|
MDS-RS-MLD, % (n/n)
|
4.8% (11/231)
|
3.2% (4/126)
|
6.7% (7/105)
|
|
|
MDS-5q-, % (n/n)
|
0.4% (1/231)
|
0.8% (1/126)
|
0.0% (0/105)
|
|
|
MDS-EB1, % (n/n)
|
26.4% (61/231)
|
27.8% (35/126)
|
24.8% (26/105)
|
|
|
MDS-EB2, % (n/n)
|
21.7% (50/231)
|
28.6% (36/126)
|
13.3% (14/105)
|
|
|
MDS-U, % (n/n)
|
6.1% (14/231)
|
5.6% (7/126)
|
6.7% (7/105)
|
|
|
IPSS-R cytogenetic risk group
|
|
|
|
χ2=2.996
|
0.559
|
Very good, % (n/n)
|
1.0% (2/196)
|
1.0% (1/97)
|
1.0% (1/99)
|
|
|
Good, % (n/n)
|
64.3% (126/196)
|
59.8% (58/97)
|
68.7% (68/99)
|
|
|
Intermediate, % (n/n)
|
20.4% (40/196)
|
24.7% (24/97)
|
16.2% (16/99)
|
|
|
Poor, % (n/n)
|
5.1% (10/196)
|
4.1% (4/97)
|
6.1% (6/99)
|
|
|
Very poor, % (n/n)
|
9.2% (18/196)
|
10.3% (10/97)
|
8.1% (8/99)
|
|
|
IPSS-R risk category
|
|
|
|
χ2=10.777
|
0.029
|
Very low, % (n/n)
|
6.6% (13/196)
|
3.1% (3/97)
|
10.1% (10/99)
|
|
|
Low, % (n/n)
|
19.4% (38/196)
|
4.1% (14/97)
|
24.2% (24/99)
|
|
|
Intermediate, % (n/n)
|
34.2% (67/196)
|
35.1% (33/97)
|
34.3% (34/99)
|
|
|
High, % (n/n)
|
21.4% (42/196)
|
23.7% (23/97)
|
19.2% (19/99)
|
|
|
Very high, % (n/n)
|
18.4% (36/196)
|
24.7% (24/97)
|
12.1% (12/99)
|
|
|
IPSS-R score[median(quartile)]
|
4.5(3.0,6.0)
|
4.75(1.5~10.0)
|
3.5(1.0~9.0)
|
Z =-3.308
|
0.001
|
Gene mutation, % (n/n)
|
62.7% (42/67)
|
72.4% (21/29)
|
55.2% (21/38)
|
χ2=2.068
|
0.150
|
Leukemia transformation, % (n/n)
|
11.2% (26/231)
|
12.7% (16/126)
|
9.5% (10/105)
|
χ2=0.578
|
0.447
|
Complex karyotype,% (n/n)
|
17.9% (35/196)
|
21.6% (21/97)
|
14.1% (14/99)
|
χ2=1.883
|
0.170
|
Abbreviations: BM, bone marrow; NE, neutrophil; HB, hemoglobin; PLT, platelet; MDS-SLD, MDS with single lineage dysplasia; MDS-MLD, MDS with multilineage dysplasia; MDS-RS-SLD, MDS with ring sideroblasts and single lineage dysplasia; MDS-RS-MLD, MDS with ring sideroblasts and multilineage dysplasia; MDS-EB1, MDS with excess blasts 1; MDS-EB2, MDS with excess blasts 2; MDS-U, unclassifiable; IPSS-R, Revised International Prognostic Scoring System. |
Low ApoA1 in relation to clinical and laboratory factors
In our cohort, the ApoA1 level was lower in 231 MDS patients than in 161 healthy donors (1.00g/L vs. 1.33g/L, P<0.0001; Figure1). MDS patients were divided into two groups to analyze the correlation between ApoA1 level and clinical and laboratory characteristics. It showed that the low ApoA1 group had significantly higher counts of BM blast (P=0.008) and lower HB (P<0.001), lower PLT (P=0.002) as well as higher risk distribution in terms of IPSS-R (P=0.029) compared with the high ApoA1 group. Also, the WHO subtype between these two groups had a significant difference (P=0.042). There were no significant differences in other factors between two groups (Table1).
Low ApoA1 was accompanied with more mutation of TP53
Mutations of 14 genes were detected in 67 patients, 42(62.7%) of whom harbored mutations.
14 genes mutation ratio as follows: ASXL1(14.9%), TP53(11.9%), RUNX1(11.9%), SF3B1(9.0%), TET2(9.0%), DNMT3A (6.0%), IDH2(4.5%), SRSF2(4.5%), NRAS (3.0%), EZH2(3.0%), CBL (3.0%), IDH1(1.5%), JAK2(1.5%) and ETV6(0.0%) (Figure2). The low ApoA1 group harbored higher ratio of gene mutation in comparison with the high ApoA1 group, but the difference was not statistically significant (72.4% vs. 55.3%, P=0.15). Among these mutations, the low ApoA1 group showed higher mutation frequency of TP53 compared with the high ApoA1 group (28.0% vs. 0.0%, P= 0.001).
Low ApoA1 was sociated with a poor prognosis
Compared with the high ApoA1 group, the median OS in the low ApoA1 group was significantly shorter (19 months vs 56 months, P<0.0001; Figure3A). But when it comes to LFS, the difference was not statistically significant (P=0.359; Figure3B).
In univariate analysis, OS was adversely associated with older age (≥60 years) (P<0.0001), male (P=0.012), higher-risk IPSS-R cytogenetic (P=0.011), higher BM blast percentage (>5%) (P<0.0001), higher IPSS-R score (P<0.0001), lower HB(<10g/dl) (P=0.004) and ApoA1 (≤1.02g/L) (P<0.0001).
Multivariate analyses showed that older age (≥60 years) (P<0.0001), higher BM blast percentage (>5%) (P=0.006), higher-risk IPSS-R cytogenetic(P=0.006) were adverse factors and low ApoA1 was a significant prognostic factor for worse OS (P=0.020). Meanwhile multivariate analyses included age, gender, IPSS-R score and ApoA1, the data showed that older age (≥60 years) (P<0.0001), higher IPSS-R score(P<0.0001) and low ApoA1(P=0.023) were adverse factors (Table2). Therefore, decreased serum ApoA1 could predict a poor prognosis independent of the IPSS-R.
Table 2
Univariate and multivariate analyses for overall survival in 231 patients with MDS
Variables
|
Univariate analysis for OS
|
Multivariate analysis for OS
|
|
P-value
|
95%CI
|
P-value
|
95%CI
|
P-value
|
95%CI
|
Age≥60(years)
|
<0.0001
|
12.522-21.478
|
<0.0001
|
0.236-0.588
|
<0.0001
|
0.244-0.595
|
Gender(male)
|
0.012
|
14.400-27.600
|
0.071
|
0.426-1.036
|
0.088
|
0.437-1.060
|
HB<10g/dl
|
0.004
|
15.481-26.519
|
0.108
|
0.911-2.562
|
-
|
-
|
NE<0.8×109/L
|
0.080
|
12.051-25.949
|
0.955
|
0.626-1.556
|
-
|
-
|
PLT<100×109/L
|
0.098
|
11.102-34.898
|
0.200
|
0.831-2.420
|
-
|
-
|
BM blast>5%
|
<0.0001
|
9.227-18.773
|
<0.0001
|
2.016-4.841
|
-
|
-
|
IPSS-R cytogenetic risk group
|
0.011
|
23.202-48.798
|
0.006
|
1.085-1.636
|
-
|
-
|
IPSS-R score
|
<0.0001
|
23.202-48.789
|
-
|
-
|
<0.0001
|
1.502-2.211
|
ApoA1≤1.02g/L
|
<0.0001
|
12.649-25.351
|
0.020
|
0.383-0.921
|
0.023
(0.020) *
|
0.389-0.933
|
Abbreviations: HB, hemoglobin; NE, neutrophil; PLT, platelet; BM, bone marrow; IPSS-R, Revised
International Prognostic Scoring System. * Multivariate analyses included age, gender, IPSS-R score
and ApoA1.
|