Association between methotrexate and white matter integritya
Tracts | Intrathecal MHAb | High-Dose Methotrexateb | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Mean Diffusivity | Fractional Anisotropy | Mean Diffusivity | Fractional Anisotropy | |||||||||
Est. | SE | P | Est. | SE | P | Est. | SE | P | Est. | SE | P | |
Corpus callosum | 0.0017 | 0.0008 | .04c | −0.0009 | 0.0007 | .21 | −0.0003 | 0.0005 | .60 | 0.0006 | 0.0004 | .17 |
Genu | 0.0016 | 0.0009 | .07 | −0.0015 | 0.0012 | .21 | −0.0001 | 0.0005 | .82 | −0.0002 | 0.0007 | .76 |
Body | 0.0008 | 0.0010 | .45 | 0.0000 | 0.0009 | .99 | −0.0008 | 0.0006 | .21 | 0.0011 | 0.0005 | .05 |
Splenium | 0.0022 | 0.0011 | .04c | −0.0011 | 0.0007 | .13 | 0.0000 | 0.0006 | .95 | 0.0007 | 0.0004 | .09 |
Corona radiata | 0.0014 | 0.0007 | .04c | −0.0004 | 0.0005 | .36 | −0.0003 | 0.0004 | .44 | 0.0002 | 0.0003 | .57 |
Anterior (left) | 0.0017 | 0.0009 | .06 | −0.0010 | 0.0005 | .06 | −0.0002 | 0.0005 | .73 | −0.0001 | 0.0003 | .75 |
Anterior (right) | 0.0011 | 0.0009 | .19 | −0.0005 | 0.0006 | .41 | −0.0005 | 0.0005 | .31 | 0.0001 | 0.0003 | .78 |
Superior (left) | 0.0013 | 0.0005 | .02c | 0.0003 | 0.0007 | .70 | −0.0001 | 0.0003 | .69 | 0.0004 | 0.0004 | .33 |
Superior (right) | 0.0015 | 0.0005 | .005c | −0.0003 | 0.0007 | .66 | −0.0002 | 0.0003 | .58 | 0.0002 | 0.0004 | .53 |
Posterior (left) | 0.0009 | 0.0007 | .23 | 0.0003 | 0.0007 | .65 | −0.0007 | 0.0004 | .08 | 0.0007 | 0.0004 | .12 |
Posterior (right) | 0.0016 | 0.0007 | .02c | −0.0002 | 0.0007 | .79 | −0.0003 | 0.0004 | .42 | 0.0002 | 0.0004 | .58 |
Posterior thalamic radiation | 0.0015 | 0.0007 | .03c | −0.0003 | 0.0007 | .63 | 0.0000 | 0.0004 | .94 | 0.0007 | 0.0004 | .11 |
Left | 0.0011 | 0.0010 | .29 | 0.0000 | 0.0008 | .98 | −0.0003 | 0.0006 | .65 | 0.0009 | 0.0005 | .05 |
Right | 0.0018 | 0.0006 | .003c | −0.0006 | 0.0007 | .42 | 0.0001 | 0.0004 | .69 | 0.0005 | 0.0004 | .24 |
Superior longitudinal fasciculus | 0.0007 | 0.0005 | .16 | 0.0006 | 0.0005 | .25 | −0.0001 | 0.0003 | .75 | 0.0005 | 0.0003 | .14 |
Left | 0.0006 | 0.0005 | .22 | 0.0008 | 0.0006 | .16 | −0.0001 | 0.0003 | .61 | 0.0004 | 0.0003 | .30 |
Right | 0.0007 | 0.0005 | .13 | 0.0005 | 0.0006 | .41 | 0.0000 | 0.0003 | .87 | 0.0006 | 0.0003 | .10 |
Superior fronto-occipital fasciculus | 0.0020 | 0.0009 | .02c | −0.0004 | 0.0009 | .65 | −0.0003 | 0.0005 | .60 | 0.0009 | 0.0005 | .09 |
Left | 0.0021 | 0.0010 | .04c | −0.0004 | 0.0009 | .63 | −0.0005 | 0.0006 | .41 | 0.0009 | 0.0005 | .10 |
Right | 0.0019 | 0.0007 | .01c | −0.0003 | 0.0010 | .73 | 0.0000 | 0.0005 | .97 | 0.0008 | 0.0006 | .14 |
Note:—Est. indicates parameter estimate; SE, standard error; MHA, methotrexate plus hydrocortisone plus cytarabine.
↵a General linear modeling was applied for the test of strength of association between treatment variables with mean diffusivity and fractional anisotropy for each tract, adjusted for age at evaluation. Higher mean diffusivity and lower fractional anisotropy are indicative of worse white matter integrity.
↵b Intrathecal MHA was defined as the number of intrathecal injections of methotrexate plus hydrocortisone plus cytarabine; high-dose IV methotrexate was defined as a daily dose of >1 g/m2, presented as cumulative doses (g/m2).
↵c Significant.