Introduction:Outcome after intestinal transplantation (ITx) remains inferior compared to other isolated organ Tx, due to the strong alloimmune response elicited by the intestinal graft, the subsequent dependence upon profound immunosuppression (IS) and its associated side effects (infection, malignancy, IS-related nephrotoxicity).

 

Aim:To redirect the alloimmune response towards graft acceptance while reducing the level of IS and as a beneficial consequence decreasing the IS side-effects.

 

Methods:The tolerogenic protocol was based on i) perioperative Donor-Specific Blood Transfusion (DSBT); ii) avoiding high-dose steroids; iii) tapering tacrolimus-levels towards a mininal dose; and iv) reduction of perioperative inflammation by bowel decontamination and glutamine administration in donors and receptors and by decreasing ischemia-reperfusion injury. 10 consecutive deceased ITx recipients were exposed to the protocol {5 isolated ITx; 5 combined liver/ITx, median age: 38.5 years (y) (2y8 months (mo)-56y8mo)}. Indications were anatomical or functional short bowel syndrome: volvulus(4), intestinal ischemia(3), Crohn(2), chronic intestinal pseudo-obstruction(1). IS was tacrolimus-based (<15 ng/ml) and gradually tapered to 5-8 ng/ml after isolated ITx or <5 ng/ml after combined liver/ITx. As induction therapy, basiliximab was used in 8 patients and ATG in 2. Analyzed end-points were: early (<3mo) and late (>3mo) Acute Rejection (AR) and Chronic Rejection (CR), nutritional independence (TPN-freedom), IS-side effects and 10y patient/graft survival (Kaplan-Meier).

 

Results:All patients were transplanted between 10/´00-12/´11. Only 1 early AR (10%) was seen in a Crohn patient, who responded to steroid treatment. Late AR was seen in 2 patients (20%) at 4mo/7mo and 46mo postTx. In the former, AR was reversible but the patient succumbed to aspergillus sepsis; in the latter, AR was due to non-compliance and was fully reversible. No CR was documented so far. The longest survivor died 11y10mo postTx due to acute diffuse NSAID-induced ulcera in the intestinal graft. At last follow-up the 8 survivors are TPN-free. No graft-versus-host disease or postTx lymphoproliferative disorder was diagnosed. None of the patients developed chronic renal insufficiency. The 10y patient/graft survival is 90%.

 

Conclusion:The immunomodulatory protocol described herein {consisting in administration of donor antigens (DSBT), in the context of an inflammatory-poor environment, and under protection of low IS} seems to promote intestinal graft acceptance resulting in less IS-side effects and improved long-term survival.