Polymorphisms of MTHFR Associated with Higher Relapse/Death Ratio and Delayed Weekly MTX Administration in Pediatric Lymphoid Malignancies
Table 4
Clinical adverse event, delayed course, and polymorphisms during MTX 3 g/m2 courses in total 149.
Gene and locus or reference SNP ID
Number of courses according to genotype
MTX concentration (mol/L)
Creatine elevation
ALT elevation
T Bil (mg/dL) 1.50
Assessable course for duration
Delayed course (more than 5 days)
at 48 hours 1.00
at 72 hours 0.10
MTHFR C677T
CC
49
4
17
8
9
11
32
8
CT/TT
100
11
32
11
41
15
69
33
0.774
0.742
0.360
0.006
0.272
0.030
MTHFR A1298C
AA
96
13
36
14
38
13
67
30
AC/CC
53
2
13
5
12
13
34
11
0.060
0.107
0.367
0.036
0.096
0.230
SLCO1B1 rs11045879
TT
66
6
21
9
25
11
45
18
TC/CC
83
9
28
10
25
15
56
23
0.687
0.805
0.773
0.319
0.796
0.913
SLCO1B1 T521C
TT
100
9
30
12
35
14
68
28
TC/CC
49
6
19
7
15
12
33
13
0.567
0.284
0.694
0.594
0.120
0.864
MTHFR 677CT/TT and 1298AA
no
27
1
9
3
5
27
18
5
yes
74
10
28
9
34
73
53
27
0.279
0.678
1.000
0.012
0.194
0.088
All assessable HD-MTX (3 g/m2) courses undergone for leukemia were 149 in total. MTHFR c.677CT/TT and c.1298AA genotype were associated to hepatotoxicity. ALT assessed as elevated as CTCAE more than grade 1. Elevated creatinine was evaluated with increased serum creatinine more than 1.5 times compared with the value just before the MTX administration.
