Higher plasma bilirubin predicts veno-occlusive disease in early childhood undergoing hematopoietic stem cell transplantation with cyclosporine

Table 1 The characteristics of hematopoietic stem cell transplantation patients treated with cyclosporine (n = 123)

Characteristics	G#1 (n = 25)	G#2 (n = 70)	G#3 (n = 28)
Age (mean, SD)	20.3, 1.7	13.0, 2.5	5.8, 2.2
Initial body weight (mean, SD)	51.8, 11.1	37.8, 12.7	14.0, 4.0
Gender (M, %)	15 (60.0)	35 (50.0)	17 (60.7)
Liver function (mean, SD)
ALT (mg/dL)	67.6, 95.8	67.1, 67.3	104, 133
AST (mg/dL)	70.2, 73.1	72.9, 61.5	161, 356
Doner types, n (%)
Cord blood	15 (60.0)	41 (58.6)	21 (75.0)
Related donor	10 (40.0)	29 (41.4)	7 (25.0)
Types of disease, n (%)
AA	5 (20.0)	6 (8.6)	1 (3.6)
ABL	4 (16.0)	5 (7.1)	2 (7.1)
ALL	10 (40.0)	28 (40.0)	7 (25.0)
AML	5 (20.0)	20 (28.6)	10 (35.7)
CML	0 (0.0)	2 (2.9)	0 (0.0)
JMML	0 (0.0)	0 (0.0)	4 (14.3)
MDS	1 (4.0)	2 (2.9)	1 (3.6)
Others	0 (0.0)	7 (10.0)	3 (10.7)
Observed events, n (%)
aGVHD	13 (61.9)	26 (46.4)	13 (54.2)
cGVHD	1 (4.8)	4 (7.1)	0 (0.0)
VOD	2 (9.5)	13 (23.2)	7 (29.2)
DIC	4 (19.0)	4 (7.2)	2 (8.3)
Relapse	1 (4.8)	2 (3.6)	1 (4.2)
EF	0 (0.0)	7 (12.5)	1 (4.2)

Age groups: G#1, 18 years older; G#2, 9 to 17 years old; G#3, 8 years old or under. AA: Aplastic anemia; ABL: Acute biphenotypic leukemia; ALL: Acute lymphocytic leukemia; AML: Acute myelocytic leukemia; CML: Chronic myelocytic leukemia; JMML: Juvenile myelomonocytic leukemia; MDS: Myelo dysplastic syndromes; aGVHD: Acute graft versus host disease; cGVHD: Chronic graft versus host disease; VOD: Veno-occlusive disease; DIC: Disseminated intravascular coagulation; EF: Engraft failure; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Table 2 Median trough plasma concentrations and doses of cyclosporine in hematopoietic stem cell transplantation patients

Contents		G#1 (n = 25)	G#2 (n = 70)	G#3 (n = 28)
iv	Trough plasma concentrationb (ng/mL)	535.6 (264.0-1214.0)a	448.9 (184.5-1070.0)	333.1 (152.5-819.0)
	Dose (mg/kg)	5.8 (3.9-7.7)	6.1 (3.5-14.2)	6.0 (3.8-9.3)
PO	Trough plasma concentrationb (ng/mL)	345.9 (166.0-686.5)	247.7 (40.0-496.5)	204.4 (33.0-302.5)
	Dose (mg/kg)c	8.2 (3.4-11.4)	8.2 (1.6-17.5)	10.6 (6.0-24.6)

^aThe values in parenthesis represent the minimum and maximum trough plasma concentrations of cyclosporine;

^bG#1 was significantly different from G#2 or G#3 using Duncan test;

^cG#3 was significantly different from G#1 or G#2 using Duncan test. iv: Intravenous administration; PO: Per Os, which means oral administration.

Table 3 Two by two analyses between maximal plasma bilirubin contents and veno-occlusive disease in hematopoietic stem cell transplantation patients

	G#1 (n = 25)		G#2 (n = 70)		G#3 (n = 28)
	BILmax (-)	BILmax (+)	BILmax (-)	BILmax (+)	BILmax (-)	BILmax (+)
VOD (+)	0	2	4	9	0	7
VOD (-)	5	18	28	29	17	4
P-value	1.00		0.356		0.0001

BILmax (+): 1.4 mg/dL or higher; BILmax (-): Lower than 1.4 mg/dL. Data were analyzed using Fisher’s test program. BILmax: A maximal total bilirubin level; VOD: Veno-occlusive disease.