“PROPE” TOLERANCE AFTER INTESTINAL TRANSPLANTATION IN MAN.

Abstract

P608 Aims: Current protocols for Intestinal Transplantation (Itx) use heavy immunosuppression (IS) but this causes infection, lymphoma and drug toxicity. “Prope” or “almost” tolerance refers to a state of graft acceptance maintained by low, non-toxic immunosuppression. To establish prope tolerance, we developed an immuno-modulatory protocol including: 1) Donor-Specific Blood Transfusion (DSBT induces regulatory cells); 2) low-dose calcineurin-inhibitor (CI) (high-dose CI prevents DSBT-induced regulatory cells generation); and 3) no steroids bolus (shown to break tolerance in a DSBT-induced tolerance model). Methods: 2 females (55 and 57 years old) with short gut and liver failure received an Itx in addition to a new liver. 300cc donor whole blood was transfused in the recipient after reperfusion. For induction IS, no iv steroids bolus were given, but only 2 doses of anti-IL-2 RA (20mg Simulect days1/4). Patients received postTx maintenance IS with very low Tac levels for this type of Tx (15ng/ml 1stmth; 5-10ng/ml 2nd-3rdmth; ∼5ng/ml thereafter), low-dose azathioprine (1mg/kg 1st–3rd mth; .5mg/kg thereafter) and low-dose steroids (medrol 8mgx2 daily tapered to 2mgx2 by the 3rdmth). Standard anti-bacterial, -fungal and -viral prophylaxis was given. Patients were monitored for rejection, GVHD, infection and PTLD. Protocol biopsies were taken from the ileal stomy. Results: Despite exposure to low IS, clinical, endoscopic and histologic signs of rejection were absent. Chimerism (donor HLA-type cells in peripheral blood) was transiently identified at day 28 in patient 1 but was self-limiting. GVHD was absent in both patients. Under this low IS, patients remained free of systemic opportunistic infections, lymphoma (no increased copies of EBV genome by PCR), and drug toxicity. Both patients are nutritionally independent and well 3 and 1.5 year postTx. Last follow-up biopsies show normal intestinal mucosa. Conclusions: The herein described immuno-modulatory protocol allowed development of “prope” tolerance and restored nutritional independence in 2 consecutive Itx recipients, a form of Tx that usually requires profound IS. Maintenance IS in these patients is less than after kidney Tx or in certain patients with chronic inflammatory bowel disease. Mechanisms of graft acceptance in these patients - in particular the development of regulatory cells - are under investigation.