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.