title: 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.affiliation: Transplant Center, Digestive Disease Institute, Cleveland Clinic, Ohio, USA. abuelmk@ccf.org
authors.forename: Kareem M
authors.initials: KM
authors.lastname: Abu-Elmagd
authors.forename: Guilherme
authors.initials: G
authors.lastname: Costa
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Bond
authors.forename: Kyle
authors.initials: K
authors.lastname: Soltys
authors.forename: Lillian
authors.initials: L
authors.lastname: Martin
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Koritsky
authors.forename: Jose R
authors.initials: JR
authors.lastname: Cunha-Melo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sogawa
authors.forename: William
authors.initials: W
authors.lastname: Irish
authors.forename: Andreas
authors.initials: A
authors.lastname: Tzakis
authors.forename: George
authors.initials: G
authors.lastname: Mazariegos
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000401:mortality*; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015994:Incidence; D007239:Infections / Q000401:mortality; D007422:Intestines / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D016035:Pancreas Transplantation / Q000401:mortality; D011817:Rabbits; D013270:Stomach / Q000637:transplantation; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab