2011 - ISBTS 2011 Symposium

Oral Communications 4: Intestinal Immunosuppression / Rejection

6.126 - rATG versus alemtuzumab single dose pretreatment for visceral allograft recipients

Presenter: Kareem, Abu-Elmagd, , United States
Authors: Kareem Abu-Elmagd1, Guilherme Costa1, Geoffrey Bond1, Ruy Cruz1, Kyle Soltys1, Rakesh Sindhi, George Mazariegos

rATG versus alemtuzumab single dose pretreatment for visceral allograft recipients

Kareem Abu-Elmagd, Guilherme Costa, Geoffrey Bond, Ruy Cruz, Kyle Soltys, Rakesh Sindhi, George Mazariegos

University of Pittsburgh Medical Center, Pittsburgh, PA, United States

Purpose: To study long-term outcome among visceral recipients pretreated with rATG or alemtuzumab as a lymphocyte depleting agent and received tacrolimus monotherapy.

Methods: On July 4, 2001, a preconditioning protocol was introduced with two therapeutic principles; recipient pretreatment with a single intravenous dose of a lymphocyte depleting agent and minimization of posttransplant immunosuppression. Depleting agents were rATG (5mg/kg) or alemtuzumab (30 mg). Postoperative immunosuppression was tacrolimus monotherapy with a target 12 hr trough level of 8-12 ng/ml. Steroids were added for patients with serum sickness, adrenal insufficiency and/or rejection. Attempts of stepwise spacing of tacrolimus dosage were made for recipients with rejection free allografts after the 4th postoperative month.

Results: As of November 30, 2010, the protocol was applied to a total of 175 adult primary visceral recipients with a mean age of 42 + 11 years. Of these, 46 (26%) received rATG and 129 (74%) received alemtuzumab. The liver was part of the visceral allograft in 34% of rATG and 26% of alemtuzumab group. Lymphocytotoxic cross-match was positive in 39% of the rATG and 28% of the alemtuzumab group. Within first 90 days, rate of histologically diagnosed and medically treated rejection was higher in rATG (50%) compared to alemtuzumab (36%) group with similar incidence (18%) of severe rejection. Chronic rejection was diagnosed in 20% of rATG and 12% of alemtuzumab with a significantly (p<0.05) lower incidence among liver contained allografts. With an overall mean follow-up of 55 + 32 months, cumulative graft survival was significantly (p=0.03) higher among alemtuzumab recipients with 1, 3, and 5 year survival rates of 92%, 75%, and 67%; respectively. In contrast, rATG respective allograft survival rates were 77%, 55%, and 46%. The risk of GVHD and CMV infection was higher with rATG (9%, 23%) compared to alemtuzumab (1%, 9%). The incidence of PTLD was similar (2%) in both groups. The success of tacrolimus spaced dosage was similar in both groups with significant (p<0.05) impact on overall posttransplant renal functions. Interestingly, a few recipients, despite successful weaning, developed opportunistic infections and de novo malignancy.

Conclusion: This study proved the superior therapeutic efficacy of alemtuzumab versus rATG single dose pretreatment among intestinal recipients with better long-term allograft acceptance.

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