Date: Monday, June 13, 2016
Session Time: 2:30pm-4:00pm
Presentation Time: 2:42pm-2:54pm
Location: Room 304
AIM: Test the hypothesis that a selected cohort of pediatric LT recipients can safely undergo complete ISW followed by assessment for operational tolerance (OT)
METHODS: 88 subjects [39(44%) male; 57(65%) deceased grafts] at 12 centers met clinical, biochemical, and histologic eligibility criteria (Fig). ISW occurred in 8 steps over 36-48 wks. ALT/GGT >100 IU/L mandated liver biopsy. OT, the 1[deg] endpoint, was defined per protocol by stable ALT, GGT and histology 1 yr after last IS dose, compared to study entry 2 yrs earlier. Associations between complete ISW and baseline clinical, immunologic (donor specific antibody) and histologic (including C4d score) factors were evaluated using logistic regression analyses.
RESULTS: 35/88 subjects failed ISW prior to OT assessment 2[deg] rejection [31 biopsy-proven (24/6/1 Banff mild/moderate/inadequate per central pathologist); 4 clinical]. No baseline clinical, immunologic or histologic factor predicted complete (n=53; 60%) vs. failed (n=35; 40%) ISW. Eight subjects are off IS for <1 yr and await OT assessment (last subject due in 3/2016). The remaining 45 subjects all met biochemical (ALT/GGT) OT criteria; 29 (64%) met histologic OT criteria [Fig]. Five subjects experienced 5 study-related serious adverse events: 3 related to liver biopsy (bile leak, cholangitis, cellulitis) and 2 related to ISW (in-patient rejection treatment with intravenous corticosteroids).
CONCLUSIONS: Selected pediatric LT recipients can safely attempt ISW. Notably, a significant proportion met biochemical but not histologic criteria for OT, suggesting a pivotal role for serial biopsies to assess for OT, detect clinically relevant graft changes and confirm long-term safety. Although baseline clinical, immunologic and histologic features did not predict ISW outcome, planned mechanistic assays may identify an OT biomarker and/or elucidate OT mechanisms.
CITATION INFORMATION: Feng S, Bucuvalas J, Demetris A, Spain K, Kanaparthi S, Magee J, Mazariegos G, The iWITH Investigators Primary Outcome of iWITH: A Multi-Center Clinical Trial of Complete Immunosuppression Withdrawal (ISW) in Stable Pediatric Liver Transplant (LT) Recipients. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Feng S, Bucuvalas J, Demetris A, Spain K, Kanaparthi S, Magee J, Mazariegos G, Investigators TheiWITH. Primary Outcome of iWITH: A Multi-Center Clinical Trial of Complete Immunosuppression Withdrawal (ISW) in Stable Pediatric Liver Transplant (LT) Recipients. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/primary-outcome-of-iwith-a-multi-center-clinical-trial-of-complete-immunosuppression-withdrawal-isw-in-stable-pediatric-liver-transplant-lt-recipients/. Accessed May 15, 2021.
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