(Supplementary information for on-line publication only)

Table 5. Comparison of the safety and efficacy of the 4 x 4 mg/kg and 4 x 150 mg/m2 BU dosing regimens in allogeneic transplant recipients with matched sibling donors.

BU dosing regimen / Significance
4 x 4 mg/kg / 4 x 150 mg/m2
No. of children / 9 / 14
Age at BMT (years)
Median (interquartile range) / 8.3
(2.8 – 11.6) / 6.6
(1.9 – 10.1) / NS1
Weight at BMT (kg)
Median (interquartile range) / 25.6
(12.5 – 40.0) / 23.2
(12.7 – 39.4) / NS1
Daily BU dose (mg/kg)
Median (Interquartile range) / 4.0 (4.0 – 4.2) / 5.6 (5.1 – 6.3) / p < 0.0011
BU AUC (µM.min)
Median (Interquartile range) / (n = 2)
3061
(2465 – 3656) / (n = 11)
7780
(5591 – 8623) / p < 0.051
No.children with AUC > 5200 µM.min / 0 (of 2)
(0%) / 9 (of 11)
(82%) / p = 0.077
No. children with AUC > 6000 µM.min / 0 (of 2)
(0%) / 7 (of 11)
(64%) / p = 0.192
No. children who achieved full or partial engraftment / 9
(100%) / 13
(93%) / NS2
No. children administered GCSF / 0 / 3 / NS2
Rate of haematological recovery
Median (interquartile range)
Days to N500
Days to N1000
Days to PL25
Days to PL50
Days to PL100 / 24 (13-27)
(n = 9)
25 (21 – 29)
(n = 9)
21 (17 – 40)
(n = 9)
24 (19 – 44)
(n = 9)
27 (22 – 72)
(n = 9) / 16 (12 – 18)
(n = 12)3
18 (15 – 28)
(n = 12)3
20 (16 – 26)
(n =11)3
25 (17 – 26)
(n = 11)3
37 (28 – 58)
(n = 10)3 / NS1
NS1
NS1
NS1
NS1
No. children who developed GVHD / 1
(11%) / 4
(29%) / NS2
No. children with VOD / 1
(11%) / 0
(0%) / NS2
No. children with grade 3 or 4 RRT / 0
(0%) / 1
(7%) / NS2
No. transfusions
Median (Interquartile range)
Platelet
blood
total / 20 (13 – 120)
1 (0 – 7)
32 (16 – 85) / 20 (11 – 58)
1 (0 – 7)
22 (12 – 65) / NS1
NS1
NS1

No. = Number, 1 Mann -Whitney Test, 2 Fishers Exact Test, 3Data from 1 child who failed to engraft but achieved full haematological recovery was not included. Data was unavailable for 1 child.

(Supplementary information for on-line publication only)

Table 6. Comparison of the safety and efficacy of the 4 x 4 mg/kg and 4 x 150 mg/m2 BU dosing regimens in autologous transplant recipients

BU dosing regimen / Significance
4 x 4 mg/kg / 4 x 150 mg/m2
Total No. children / 164 / 24
Age at BMT (years)
Median (Interquartile range) / 8.8
(4.4 – 13.7) / 6.6
(2.3 – 11.7) / NS1
Weight at BMT (kg)
Median (Interquartile range) / 27.9
(19.2 – 48.7) / 21.4
(13.8 – 32.9) / NS1
No. children who relapsed / 7 (of 15)
(47%) / 9
(38%) / NS2
No. children who relapsed early3 / 1 (of 15)
(7%) / 4
(17%) / NS2
Daily BU dose (mg/kg)
Median (Interquartile range) / 4.0 (3.9 – 4.1) / 6.1 (5.3 – 6.5) / p < 0.0011
BU AUC (µM.min)
Median (Interquartile range) / (n = 5)
4833
(4023 – 5377) / (n = 16)
6852
(5386 – 8425) / p < 0.051
No. children with AUC > 5200 µM.min / 2 (of 5)
(40%) / 13 (of 16)
(81%) / p = 0.1151
No. children with AUC > 6000 µM.min / 0 (of 5)
(0%) / 11 (of 16)
(69%) / p < 0.051
No. children administered GCSF / 0 / 5 / NS2
Rate of haematological recovery
Median (Interquartile range)
Days to N500
Days to N1000
Days to PL25
Days to PL50
Days to PL100 / 19 (14 – 37)
(n = 15)
42 (20 – 56)
(n = 15)
52 (38 – 59)
(n = 15)
59 (47 – 81)
(n = 15)
88 (65 – 167)
(n = 13) / 18 (12 – 40)
(n = 24)
44 (17 – 51)
(n = 23)
41 (35 – 66)
(n = 20)
51 (41 – 84)
(n = 20)
71 (56 – 131)
(n = 17) / NS1
NS1
NS1
NS1
NS1
No. children with VOD / 1 (of 15)
(7%) / 1
(4%) / NS2
No. children with grade 3 or 4 RRT / 1 (of 15)
(7%) / 1
(4%) / NS2
No. transfusions
Median (Interquartile range)
Platelet
blood
total / 64 (42 – 79)
4 (1 – 5)
67 (46 – 85) / 40 (25 – 78)
2 (1 - 5)
44 (27 – 81) / NS1
NS1
NS1

No. = Number, 1 Mann -Whitney Test, 2 Fishers Exact Test, 3 Relapse occurred prior to 90 days post transplant, 4 One child who had 4 x 4 mg.kg-1 BU could not be evaluated for haematological recovery, VOD, relapse, RRT or transfusions due to early death from sepsis.

(Supplementary information for on-line publication only)

Table 7. Comparison of the safety and efficacy of 4 x 150 mg/m2 BU in younger (< 3years) and older (> 5years) allogeneic transplant recipients.

Age group / Significance
< 3 years / > 5 years
Total No. of children / 4 / 9
No. children with full or partial engraftment / 3
(75%) / 9
(100%) / NS2
No. children who developed GVHD / 2
(50%) / 2
(22%) / NS2
Single daily BU dose (mg.kg-1)
Median (Interquartile range) / 6.9 (6.3 – 7.8) / 5.3 (4.4 – 5.7) / p < 0.0051
No. patients administered GCSF / 2 / 1 / NS2
Rate of engraftment
Median (Interquartile range)
Days to N500
Days to N1000
Days to PL25
Days to PL50
Days to PL100 / 16 (15 – 18)
(n = 3)
21 (15 – 29)
(n = 3)
20 (14 – 36)
(n = 3)
26 (17 – 40)
(n = 3)
53 (35 – 105)
(n = 3) / 15 (12 – 18)
(n = 8)
18 (15 – 31)
(n = 8)
19 (16 – 25)
(n = 7)
19 (16 – 26)
(n = 7)
33 (24 – 51)
(n = 6) / NS1
NS1
NS1
NS1
NS1
No. children with VOD / 0 / 0 / NS2
No. children with grade 3 or 4 RRT / 0 / 1 / NS2
No. transfusions
Median (Interquartile range)
Platelet
blood
total / (n = 4)
45 (13 – 97)
6 (2 – 11)
51 (15 – 108) / (n = 8)
33 (17 – 80)
1 (0 – 3)
33 (17 - 84) / NS1
NS1
NS1

No. = Number, 1 Mann -Whitney Test, 2 Fishers Exact Test

(Supplementary information for on-line publication only)

Table 8. Comparison of the safety and efficacy of 4 x 150 mg/m2 BU in younger (< 3years) and older (> 5years) autologous transplant recipients.

Age group / Significance
< 3 years / > 5 years
Total No. of children / 8 / 15
No. children who relapsed / 1 (13%) / 7 (47%) / NS2
No. children who relapsed early3 / 0 / 3 / NS2
Single daily BU dose (mg.kg-1)
Median (Interquartile range) / 6.5 (6.4 – 7.4) / 5.5 (4.6 – 5.9) / p < 0.0051
No. patients administered GCSF / 2 / 2 / NS2
Rate of haematological recovery
Median (Interquartile range)
Days to N500
Days to N1000
Days to PL25
Days to PL50
Days to PL100 / 19 (12 – 32)
(n = 8)
38 (23 – 57)
(n = 8)
39 (30 – 64)
(n = 7)
55 (41 – 87)
(n = 7)
64 (55 – 128)
(n = 7) / 16 (12 – 42)
(n = 15)
43 (16 – 50)
(n = 14)
42 (36 – 71)
(n =13)
46 (40 – 84)
(n = 13)
86 (56 – 141)
(n = 10) / NS1
NS1
NS1
NS1
NS1
No. children with VOD / 1 / 0 / NS2
No. children with grade 3 or 4 RRT / 1 / 0 / NS2
No. transfusions
Median (Interquartile range)
Platelet
blood
total / (n = 8)
40 (20 – 58)
3 (1 – 5)
43 (22 – 61) / (n = 13)
47 (25 – 86)
2 (1 – 4)
48 (27 - 90) / NS1
NS1
NS1

No. = Number, 1 Mann -Whitney Test, 2 Fishers Exact Test 3Relapse occurred prior to 90 days post transplant.