The effect of intravenous hydration strategy on plasma methotrexate clearance during intravenous high-dose methotrexate administration in pediatric oncology patients

Figures & data

Table 1 Patient characteristics

Patients (n=37)	Mean ± SD	Median (Min–Max)
Age (years)	8.3±4.2	9 (1–14)
Gender, n (%)
Male	25 (67.6)
Female	12 (32.4)
Weight (kg)	34.9±15.4	33.4 (10–84.2)
Height (cm)	136.3±22.8	141.2 (80–168.1)
BSA (m^2)	1.14±0.33	1.10 (0.50–2.00)
Length of stay (days)	8.3±3.9	7 (4–25)
ALL (n=18 with 56 HD-MTX courses)
Age (years)	7.0±4.8	5.5 (1–14)
Gender, n (%)
Male	12 (66.7)
Female	6 (33.3)
Weight (kg)	33.3±23.2	21 (10–84.2)
Height (cm)	120.8±27.4	118.2 (80–165)
BSA (m^2)	1.03±0.47	0.84 (0.47–1.96)
Length of stay (days)	5.9±1.7	5 (5–15)
NHL (n=7 with 34 HD-MTX courses)
Age (years)	7.9±2.3	9 (5–11)
Gender, n (%)
Male	6 (85.7)
Female	1 (14.3)
Weight (kg)	28.5±8.4	28.1 (18–45.7)
Height (cm)	129.6±12.5	128.1 (109–146.5)
BSA (m^2)	1.01±0.19	1.01 (0.74–1.36)
Length of stay (days)	9.1±4.2	9 (4–24)
Osteosarcoma (n=12 with 75 HD-MTX courses)
Age (years)	11.2±2.2	12 (8–14)
Gender, n (%)
Male	7 (58.3)
Female	5 (41.7)
Weight (kg)	37.6±8.5	39.5 (23.6–57)
Height (cm)	148.6±12.9	153 (126–168)
BSA (m^2)	1.24±0.19	1.30 (0.91–1.57)
Length of stay (days)	9.7±4.2	9 (4–25)

Note: Data are shown as mean ± SD or median (range) for continuous variables and number (%) for categorical variables.

Abbreviations: ALL, acute lymphoblastic leukemia; BSA, body surface area; HD-MTX, high-dose methotrexate; NHL, non-Hodgkin’s lymphoma.

Table 2 intravenous hydration administrations in cancer-specific HD-MTX chemotherapy regimens

Cancer types	HD-MTX treatment courses (N=165)
	Hydration <3,000 mL/m^2/day	Hydration ≥3,000 mL/m^2/day
ALL	41	15
NHL	14	20
Osteosarcoma	62	13
Total	117	48

Note: Data are shown as number for categorical variables.

Abbreviations: ALL, acute lymphoblastic leukemia; HD-MTX, high-dose methotrexate; NHL, non-Hodgkin’s lymphoma.

Table 3 The correlation between 72-hour methotrexate levels and associated factors in disease-specific HD-MTX regimens

HD-MTX courses	Plasma methotrexate level at 72 hours after the initiation of HD-MTX (μmol/L)
	ALL			NHL			Osteosarcoma
	<0.1 (n=55, %)	≥0.1 (n=1, %)	P-value	<0.1 (n=23, %)	≥0.1 (n=11, %)	P-value	<0.1 (n=52, %)	≥0.1 (n=23, %)	P-value
Gender
Male	41 (74.5)	0 (0.0)	0.612	16 (69.6)	9 (81.8)	0.449	34 (65.4)	18 (78.3)	0.265
Female	14 (25.5)	1 (100.0)		7 (30.4)	2 (18.2)		18 (34.6)	5 (21.7)
Hydration (mL/m^2)
<3,000	40 (72.7)	1 (100.0)	1.000	10 (43.5)	4 (36.4)	0.693	39 (75.0)	23 (100.0)	0.007*
≥3,000	15 (27.3)	0 (0.0)		13 (56.5)	7 (63.6)		13 (25.0)	0 (0.0)
HCO3 (mEq/L)
<24	37 (67.3)	0 (0.0)	0.245	12 (52.2)	3 (27.3)	0.171	20 (38.5)	12 (52.2)	0.317
≥24	18 (32.7)	1 (100.0)		11 (47.8)	8 (72.7)		32 (61.5)	11 (47.8)
Urine spgr
>1.010	49 (89.1)	1 (100.0)	0.442	22 (95.7)	11 (100.0)	0.483	3 (5.8)	1 (4.3)	1.000
≤1.010	6 (10.9)	0 (0.0)		1 (4.3)	0 (0.0)		49 (94.2)	22 (95.7)
Methotrexate duration (hours)
4	30 (54.5)	0 (0.0)	1.000	14 (60.9)	7 (63.6)	0.877	52 (100.0)	23 (100.0)	N/A
24	25 (45.5)	1 (100.0)		9 (39.1)	4 (36.4)		0 (0.0)	0 (0.0)
Adverse reactions
Mucositis	5 (9.1) 5	0 (0.0) 0	N/A	3 (13.0) 3	5 (45.5) 3	N/A	0 (0.0) 1	2 (8.7) 0	N/A
BM suppression	(9.1) 0	(0.0) 0	N/A	(13.0) 0	(27.3) 1	N/A	(1.9) 0	(0.0) 0	N/A
Renal toxicity	(0.0) 1	(0.0) 0	N/A	(0.0) 1	(9.1) 1	N/A	(0.0) 8	(0.0) 6	N/A
Liver toxicity	(1.8)	(0.0)	N/A	(4.3)	(9.1)	N/A	(15.4)	(26.1)	N/A

Notes: Data are shown as number (%). P-value was obtained from chi-squared test for data with a parametric distribution and Fisher’s exact test for nonparametric distribution.

* P-value <0.05 is statistically significant.

Abbreviations: ALL, acute lymphoblastic leukemia; BM, bone marrow; HD-MTX, high-dose methotrexate; N/A, not available; NHL, non-Hodgkin’s lymphoma; spgr, specific gravity.

Figure 1 The effect of intravenous hydration on 72-hour plasma methotrexate levels (μmol/L) in osteosarcoma patients.

Notes: Data in the graph are shown as dot plots. One dot plot represents one course of HD-MTX administration in osteosarcoma protocol.

Abbreviation: MTX, methotrexate.