Polymorphisms of MTHFR Associated with Higher Relapse/Death Ratio and Delayed Weekly MTX Administration in Pediatric Lymphoid Malignancies

Table 5

MTX concentrations and ALT/Cre/T-Bil elevations evaluated for 147 courses in total.

MTX serum concentrations		Number of courses according to MTX concentrations	Creatinine ratio >1.5	ALT elevation CTCAE Grade more than 1	Bilirubin elevation >1.5 (mg/dL)	Assessable course for duration	Delayed duration (more than 5 days)
48 hour	<1.0 𝜇mol/L	132	10	46	20	87	31
	>1.0 𝜇mol/L	15	8	3	5	12	9
		𝑃	0.000	0.248	0.138	𝑃	0.013
72 hours	<0.1 𝜇mol/L	100	7	34	13	61	22
	>0.1 𝜇mol/L	49	12	16	13	41	19
		𝑃	0.003	0.870	0.044	𝑃	0.252

One MTX concentration less than 0.1 𝜇mol/L at 48 hours.
Higher MTX concentration at 48 hours were associated to creatinine ratio and bilirubin elevation and MTX concentration at 72 hours were associated with creatinine elevation. No associations between MTX concentration and ALT elevations were found. One patient developed renal toxicity needing hemodialysis whose MTX concentration at 48 hours was 42.71 𝜇mol/L, worst creatinine was 11.9 times higher than before treatment, worst serum ALT was 77 IU/L and total bilirubin was 1.7 mg/dL. This patient never underwent another HD-MTX treatment again.