Table 1 Characteristics of included studies

Faraci (2017) [20]

Italy

retrospective

2.9 (1.56–9.9)

NR

iv 0.8–1.2 mg/kg (q6h*4d); po 16 mg/kg or 480 mg/m²(q6h*4d)

0,1, 2, 4, and 6 h after the start of infusion/HPLC-UV

48.8 (0.4–139)

Okamoto (2014) [23]

Japan

prospective

6 (0.5–17)

AML (10); ALL (4); CML (2); JMML (5); Others (4)

iv 0.8–1.2 mg/kg (q6h*4d)

1, 2, 2.25, 2.5, 3, and 6 h after the start of infusion/GC-MSD

1,2, 2.5, and 6 h after dose 9; 0, 2.5and 6 h after dose 13/GC-MS

≥3.33

Maheshwari (2013) [13]

USA

prospective

6.2 (1.2–15.5)

SCD

iv1.0 mg/kg or 0.8 mg/kg (q6h*4d)

2, 2.25,2.5,3, 4, 5 and 6 h after the start of infusion/GC-MS

36 (14.4–72)

Veal (2012) [24]

UK

prospective

mean3.6

NB

po 1.45 or 1.55 mg/kg (q6h*4d) iv 0.8–1.2 mg/kg (q6h*4d)

1, 2.25, 2.5, 3 and 6 h after the start of infusion for doses 1 and 9; 0, 2.5, 6 h after the start of infusion for dose 13/GC-MS

≥60

^cMichel (2011) [14]

France

prospective

–

AML (17); SCD (7); CML (3); NB (27); others (10)

iv 0.8–1.2 mg/kg (q6h*4d)

NR/GC-MS

–

^dWall (2009) [15]

USA

prospective

–

AML (8); JMML (2); MDS (2); β-thalassemia (3); Others (9)

iv1.0 mg/kg or 0.8 mg/kg (q6h*4d)

2,3,4,5,6 h after the start of infusion for doses 1 and 9;2 and 6 h after the start of infusion for doses 13 /GC-MS

10.2 (2–23.2)

Vassal (2008) [16]

France

prospective

5.6 (0.3–17.2)

NB (24); AML (14); SCD (5); EWS (3); CML (3); Others (6)

iv 0.8–1.2 mg/kg (q6h*4d)

0, 1, 2, 2.25, 2.5, 3 and 6 h after the start of infusion for doses 1 and 9;0, 2.25 and 6 h after the start of infusion for doses13/GC-MS

NR

^eBouligand (2003) [25]

France

retrospective

4.4 (1.1–15.7)

malignant solid tumor

po 37.5 mg/m ² (q6h*4d)

0.5, 2 and 6 h after the start of infusion for dose 1;

6 h after the start of infusion for dose 2, 3, 4, 12,13/GC-MS

NR

Reference

Country

Study design

Age (y)^a

Diagnosis

Dosing

Sampling and analysis

^bFollow-up (months)

^fMcCune (2003) [2]

USA

retrospective

6 (0.25–16)

AML (19); MDS (7); SCID (5); others (22)

po total dose 11–28 mg/kg (q6h*4d)

0, 1, 2, 3, 4, 6 h after the start of infusion for dose 5 and dose 9/GC-MS

NR

^fBolinger (2001) [26]

USA

prospective

(0.6–17.1)

AML (6); CML (5); β-thalassemia (3); AA (4); SCD (4); others (10)

po total dose 10.9–28.9 mg/kg

0.5, 1, 2, 3, 4, 5, 6 h after the start of infusion for dose 1; 0, 0.5, 1, 2, 4, 6 h after the start of infusion for dose 5, 9 and 13/GC-MS

NR

Bolinger (2000) [17]

USA

prospective

(0.6–18)

β-thalassemia (10); AML (9); others (13)

po total dose 14–20 mg/kg

0, 0.5, 1, 2, 3, 4, 5 and 6 h after the start of infusion for dose 1 and dose 13/GC-MS

NR

Tran (2000) [29]

USA

prospective

7.6 (0.8–18)

ALL (13); AML (7); MDS (3); CML (1); NHL (1)

po 40 mg/m²

0, 0.5, 1, 2, 4, 6 h after the start of infusion for dose 1, dose 5 and dose 9/HPLC-UV

32 (11–52)

VASSAL (1996) [27]

France

retrospective

5.9 (1–15)

NB (28); Brain tumors (13); NHL (5); others (11)

po 1 mg/kg or 30–37.5 mg/m²

20 min, 40 min as well as 1, 1.5, 2, 3, 4, and 6 h after the start of infusion for dose 1, dose 5 and dose 9/GC-MS

NR