De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature

Table 4 Clinical operational tolerance trials in pediatric orthotopic liver transplant recipients

First author	Yr	Type of study	Number of patients	DNM-Patients indicated to withdraw IS	Complete IS weaning, %	Time interval: OLT to withdrawal, mo/yr	Rejection rate, for acute, %
Ramos et al[110]	1995	Prospective	20 (12-20 yr at entry) (59 total patients)	2	27.10%	> 5 yr	20.3%
Mazariegos et al[157]	1997	Historical cohort (self-weaned) and prospective cases	31 (≤ 20 yr) (100 total patients)	12	Pediatric cohort: 29%	> 5 yr	10%
Takatsuki et al[111]	2001	Prospective	63	NA	38.1%	≥ 2 yr	25.4%
Oike et al[112]	2002	Prospective	115	NA	42.6%	≥ 2 yr	20%
Koshiba et al[113]	2007	Retrospective	581	NA	15%	≥ 2 yr	1.5%
Ohe et al[114]	2012	Historical cohort	190	NA	44.2%	≥ 2 yr	26.3%
Hurwitz et al[116]	2004	Retrospective	38	19 (PTLD)	21% (n = 4 PTLD; n = 4 EBV)	Mean time to PTLD onset: 1.8 ± 2.3 yr; Mean time to EBV infection onset: 1.1 ± 1.1 yr	55.2%
Lee et al[117]	2009	Prospective	5	1 (PTLD)	100%	1.2-2 yr	0%
Feng et al[118,158] (WISP-R trial)	2012	Prospective	20	NA	60%	≥ 4 yr	35%
Feng et al[159] (iWITH trial, partial results, 2016)	2012	Prospective	88	NA	60%	≥ 4 yr	40%
Waki et al[120]	2013	Retrospective	52	NA	42.5%	> 2 yr	57.5%
Lin et al[121]	2015	Prospective	16	NA	40%	> 2 yr	40%

OLT: Orthotopic liver transplant; DNM: De novo malignancy; IS: Immunosuppression; PTLD: Post-transplant lymphoproliferative diseases; EBV: Epstein-Barr virus; NA: Not available.