A decade of experience with a single dose of rabbit antithymocyte globulin or alemtuzumab pretreatment for intestinal and multivisceral transplantation.

Abstract

In 2001, we hypothesized that recipient pretreatment with a single-dose of an anti-lymphoid depleting agent followed by tacrolimus monotherapy could promote alloengraftment with minimal long-term immunosuppression. As of November 2010, the protocol was applied to 175 adults: 46 (26%) received rATG (5 mg/kg) and 129 (74%) received alemtuzumab (30 mg). Targeted 12-hour tacrolimus trough levels were 10-15 ng/mL followed by attempts of spaced-dose reduction in selected patients. Steroids were limited to recipients with serum sickness, adrenal insufficiency, and rejection. With a 13% re-transplantation rate, overall 1-, 5-, and 10-year survival was 93%, 70%, and 50% for patients with respective graft survival of 86%, 57%, and 48%. Rejection and infection continued to be leading causes of graft loss. With better patient (p = 0.04) and graft (p = 0.03) survival among alemtuzumab-pretreated patients, cumulative risk of end-stage acute/chronic rejection was similar (p = 0.4) between both antibody cohorts. Tacrolimus spaced-dose reduction was sustainable in 56% of current survivors with 40% of the total population continuing to be steroid-free. However, few of these recipients experienced life-threatening infections and de-novo malignancy. Despite an increase in long-term survival and achievement of partial 'prope' tolerance reported herein, innovative immunosuppressive strategies along with availability of reliable tolerance assays are still required to further improve long-term visceral allograft acceptance.

• Authors: Kareem M Abu-Elmagd, Guilherme Costa, Geoffrey J Bond, Kyle Soltys, Lillian Martin, Darlene A Koritsky, Jose R Cunha-Melo, Hiroshi Sogawa, William Irish, Andreas Tzakis, George Mazariegos
• Journal: Clinical transplants (Clin Transpl) Pg. 155-66 ( 2012) ISSN: 0890-9016 [Print] United States
• PMID: 23721018 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antilymphocyte Serum
• Antineoplastic Agents
• Immunosuppressive Agents
• Alemtuzumab

Topics

• Adolescent
• Adult
• Alemtuzumab
• Animals
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antilymphocyte Serum (administration & dosage)
• Antineoplastic Agents (administration & dosage)
• Female
• Graft Rejection (drug therapy, mortality)
• Graft Survival (drug effects)
• Graft vs Host Disease (mortality)
• Humans
• Immunosuppressive Agents (administration & dosage)
• Incidence
• Infections (mortality)
• Intestines (transplantation)
• Male
• Middle Aged
• Morbidity
• Pancreas Transplantation (mortality)
• Rabbits
• Stomach (transplantation)
• Transplantation, Homologous
• Young Adult