Post-transplant lymphoproliferative disorder after liver transplantation: Incidence, long-term survival and impact of serum tacrolimus level

Table 1 Baseline characteristics of patients

	Pediatrics	Adults	Overall
Number	40	13	53
Mean age in years	5.05 ± 4.43	42 ± 13.39	14.11 ± 17.71
Sex, male/female	23/17	10/3	33/20
Allograft
Living donor	28	0	28
Deceased donor	12	13	25
Presenting sign and symptoms
LAP	18	9	27
Fever	13	1	14
Abdominal pain	15	3	18
Diarrhea	5	0	5
Weight loss	0	1	1
Cough and dyspnea	1	0	1
Bowel obstruction	1	0	1
Unilateral weakness	1	0	1
Underlying liver disease
HBV cirrhosis	0	5	5
Cryptogenic cirrhosis	0	2	2
PSC	0	2	2
HCV cirrhosis	0	1	1
AIH	2	1	3
Wilson’s disease	1	0	1
PFIC	5	0	5
Crigler-Najjar syndrome	8	0	8
Biliary atresia	12	0	12
Tyrosinemia	10	0	10
Budd-Chiari syndrome	1	1	2
Liver metastasis	0	1	1
Neonatal hepatitis	1	0	1
Immunosuppressive regimen
Prednisolone	39	12	49
Tacrolimus	36	10	46
Mycophenolate mofetil	15	11	26
Cyclosporine	1	4	5
Sirolimus	35	8	43

AIH: Autoimmune hepatitis; LAP: Lymphadenopathy; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PFIC: Progressive familial intrahepatic cholestasis; PSC: Primary sclerosing cholangitis.

Table 2 Kaplan-Meier analysis of risk factors and post-transplant lymphoproliferative disorder survival of pediatric and adult patients

	Mean survival in mo	P value
Sex		0.902
Male	65.65 ± 13.18
Female	36.06 ± 5.30
Multi-organ involvement		0.002
(+)	27.13 ± 6.30
(-)	104.25 ± 9.08
CMV status		0.370
CMV-positive	51.98 ± 10.50
CMV-negative	23.29 ± 5.76
EBV status		0.002
EBV-positive	60.58 ± 7.62
EBV-negative	16.72 ± 5.66
Rejection episode		0.762
(+)	64.90 ± 13.78
(-)	65.86 ± 15.76
Time to PTLD development in years		0.704
≤ 1	62.18 ± 14.03
≥ 1	75.13 ± 12.49
Type of allograft		0.904
Living donor	50.56 ± 6.95
Deceased donor	60.32 ± 14.33

CMV: Cytomegalovirus; EBV: Epstein-Barr virus; PTLD: Post-transplant lymphoproliferative disorder.

Table 3 Kaplan-Meier analysis of risk factors and post-transplant lymphoproliferative disorder survival of pediatric patients

	Mean survival in mo	P value
Sex		0.749
Male	41.41 ± 7.38
Female	35.85 ± 5.76
Multi-organ involvement		0.002
(+)	25.82 ± 6.90
(-)	67.62 ± 5.56
CMV status		0.139
CMV-positive	58.82 ± 9.56
CMV-negative	19.35 ± 6.21
EBV status		0.002
EBV-positive	60.58 ± 7.62
EBV-negative	5.58 ± 2.72
Rejection episode		0.888
(+)	43.61 ± 8.49
(-)	36.02 ± 5.24
Time to PTLD development in years		0.326
≤ 1	39.72 ± 6.86
≥ 1	36.45 ± 5.30
Type of allograft		0.806
Living donor	50.56 ± 6.95
Deceased donor	37.37 ± 8.11

CMV: Cytomegalovirus; EBV: Epstein-Barr virus; PTLD: Post-transplant lymphoproliferative disorder.

Table 4 Cox regression analysis showing association of different risk factors and post-transplant lymphoproliferative disorder survival of pediatric patients

	Mean	OR	95%CI	P value
Age in years	5.05	0.94	0.82-1.08	0.434
Time to PTLD in months	15.63	0.96	0.91-1.02	0.242
Tacrolimus level	14.99	1.07	1.006-1.15	0.032
Tacrolimus dose	3.81	1.06	0.67-1.66	0.797
Prednisolone dose	10.12	0.99	0.86-1.13	0.897

PTLD: Post-transplant lymphoproliferative disorder.

Table 5 Influence of different continuous variables on time to post-transplant lymphoproliferative disorder development, mortality and multi-organ involvement of post-transplant lymphoproliferative disorder patients

	Mean rank PTLD development ≤ 1 yr	Mean rank PTLD development ≥ 1 yr	U value	Z score	P value
Age	19.85	21.85	158	-0.50	0.61
Post-PTLD survival	20.19	21.15	167	-0.24	0.80
Tacrolimus level	16.57	14.61	86	-0.54	0.58
Tacrolimus dose	19.84	18.85	154	-0.27	0.78
Prednisolone dose	20.56	18.88	154	-0.44	0.65
	Alive patient	Deceased patient
Age	23.19	16.47	127.5	-1.78	0.74
Tacrolimus level	13.62	21.00	55	-2.11	0.03
Tacrolimus dose	18.96	20.43	175	-0.40	0.68
Prednisolone dose	19.65	20.57	171	-0.25	0.79
Mean time to PTLD	23.12	16.56	129	-1.74	0.08
	Multi-organ (+)	Multi-organ (-)
Age	19.50	19.50	176	0.00	1.00
Tacrolimus level	16.50	14.74	97	-0.54	0.58
Tacrolimus dose	20.27	18.14	146	-0.60	0.54
Prednisolone dose	19.81	19.27	171	-0.15	0.87
Post-PTLD survival	15.59	22.34	113	-1.85	0.06
Mean time to PTLD	13.62	23.77	82	-2.78	0.005

PTLD: Post-transplant lymphoproliferative disorder.

Table 6 Influence of different risk factors on time to post-transplant lymphoproliferative disorder development

	PTLD development ≤ 1 yr	PTLD development ≥ 1 yr	P value
All PTLD patients
Sex			0.150
Male	17	16
Female	14	6
Multi-organ involvement			0.007
(+)	15	3
(-)	14	18
CMV status			0.186
CMV-positive	9	4
CMV-negative	11	1
EBV status			0.296
EBV-positive	12	5
EBV-negative	8	1
Rejection episode			0.399
(+)	15	9
(-)	16	13
Mortality			0.324
(+)	13	7
(-)	18	15
Type of allograft			0.118
Living donor	19	9
Deceased donor	12	13
Pediatric PTLD patients
Sex			0.496
Male	15	8
Female	12	5
Multi-organ involvement			0.018
(+)	14	2
(-)	11	11
CMV status			0.368
CMV-positive	9	3
CMV-negative	9	1
EBV status			0.184
EBV-positive	12	5
EBV-negative	6	0
Rejection episode			0.587
(+)	13	6
(-)	14	7
Mortality			0.120
(+)	13	3
(-)	14	10
Type of allograft			0.609
Living donor	19	9
Deceased donor	8	4

CMV: Cytomegalovirus; EBV: Epstein-Barr virus; PTLD: Post-transplant lymphoproliferative disorder.

Table 7 Influence of different risk factors on mortality after post-transplant lymphoproliferative disorder

	Alive patient	Deceased patient	P value
All PTLD patients
Sex			0.491
Male	10	13
Female	13	7
Multi-organ involvement			0.001
(+)	6	12
(-)	26	6
CMV status			0.284
CMV-positive	9	4
CMV-negative	6	6
EBV status			0.042
EBV-positive	13	4
EBV-negative	3	6
Rejection episode			0.600
(+)	15	9
(-)	18	11
Type of allograft			0.485
Living donor	18	10
Deceased donor	15	10
Pediatric PTLD patients
Sex			0.424
Male	13	10
Female	11	6
Multi-organ involvement			0.001
(+)	5	11
(-)	19	3
CMV status			0.110
CMV-positive	9	3
CMV-negative	4	6
EBV status			0.018
EBV-positive	13	4
EBV-negative	1	5
Rejection episode			0.525
(+)	11	8
(-)	13	8
Type of allograft			0.309
Living donor	18	10
Deceased donor	6	6

CMV: Cytomegalovirus; EBV: Epstein-Barr virus; PTLD: Post-transplant lymphoproliferative disorder.

Table 8 Influence of different risk factors on multi-organ involvement in patients with post-transplant lymphoproliferative disorder

	Multi-organ involvement (+)	Multi-organ involvement (-)	P value
All PTLD patients
Sex			0.421
Male	12	19
Female	6	13
CMV status			0.418
CMV-positive	6	7
CMV-negative	7	5
EBV status			0.008
EBV-positive	5	11
EBV-negative	8	1
Rejection episode			0.448
(+)	9	14
(-)	9	18
Type of allograft			0.235
Living donor	8	19
Deceased donor	10	13
Pediatric PTL patients
Sex			0.206
Male	11	11
Female	5	11
CMV status			0.335
CMV-positive	5	7
CMV-negative	6	4
EBV status			0.006
EBV-positive	5	11
EBV-negative	6	0
Rejection episode			0.520
(+)	8	10
(-)	8	12
Type of allograft			0.019
Living donor	8	19
Deceased donor	8	3

CMV: Cytomegalovirus; EBV: Epstein-Barr virus; PTLD: Post-transplant lymphoproliferative disorder.