Table 1.
Characteristics of included studies
| Reference | Country | Study design | Age (y)a | Diagnosis | Dosing | Sampling and analysis | bFollow-up (months) |
|---|---|---|---|---|---|---|---|
| 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 |
NR Not reported, GC-MS Gas chromatography with mass spectrometry detection, IV Intravenous, HPLV-UV High-performance liquid chromatography (HPLC) with the ultraviolet (UV) detection, AA Aplastic anemia, NB Neuroblastoma, AML Acute myeloid leukemia, ALL Acute lymphocytic leukemia, MDS Myelodysplastic syndrome, NHL Non-Hodgkin’s lymphoma, SCD Sickle cell disease, SCID Severe combined immunodeficiency syndrome, EWS Ewing’s sarcoma, JMML Juvenile myelomonocytic leukemia; a age was represented as median (range) or mean ± SD; bFollow-up (moths) was represented as median (interquartile range); c31 patients in the autologous group (aged 0.7 to 14.9 years; median, 4 year), follow up with (49.1 to 56.9 months; median, 52.3 months) and 36 in allogeneic group, (aged 0.3 to 17.2 years old; median, 7.5 years).follow up with (45.5 to 52.8 months; median, 48.5 months);d 13 patients in the ≤4 years group, (aged 0.5 to 3.8 years; median, 1.6 year) and 11 patients in the> 4 years group, (aged 4.5 to 16.7; midian 10.7 years old); d 13 patients in the ≤4 years group, (aged 0.5 to 3.8 years; median, 1.6 year) and 11 patients in the> 4 years group, (aged 4.5 to 16.7; midian 10.7 years old); e Bu with MEL group had received more prior chemotherapy courses were not considered for this article; f 31 patients were accessible for efficacy (one patient older than 18 was not included)