Tacrolimus is more effective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antilymphocyte antibody preparations. Tacrolimus was associated with a higher incidence of neurologic events, which were rarely treatment limiting, and with posttransplant diabetes mellitus, which was reversible in some patients.

The toxicity of chronic immunosuppressive agents required for organ transplant maintenance has prompted investigators to pursue approaches to induce immune tolerance. We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSC) and tolerogenic CD8+/TCR− graft facilitating cells (FC) combined with nonmyeloablative conditioning that allows engraftment, durable chimerism, and tolerance induction in highly mismatched related and unrelated donor-recipient pairs. Eight recipients of HLA-mismatched kidney and FC/HSC transplants underwent conditioning with fludarabine, 200 cGy total body irradiation, and cyclophosphamide followed by post-transplant immunosuppression with tacrolimus and mycophenolate mofetil. Subjects ranged in age from 29 to 56 years. HLA match ranged from 5 of 6 related to 1 of 6 unrelated. The absolute neutrophil counts nadired approximately one week after transplant, with recovery by two weeks. Multilineage chimerism at one month was 6% to 100%. The conditioning was well tolerated with outpatient management after postoperative day two. Two subjects exhibited transient chimerism and have been reduced to low-dose tacrolimus monotherapy. One subject developed viral sepsis two months after transplant and experienced renal artery thrombosis. Five subjects have durable chimerism, with immunocompetence and donor-specific tolerance by in vitro proliferative assays and were successfully weaned off all immunosuppression one year after transplant. None of the recipients produced anti-donor antibody or exhibited engraftment syndrome or graft-versus-host disease. These results suggest that manipulation of a mobilized stem cell graft and nonmyeloablative conditioning represents a safe, practical, and reproducible means of inducing durable chimerism and donor-specific tolerance in solid organ transplant recipients.

Tacrolimus-based therapy resulted in significantly reduced risk of graft failure, without an increase in the incidence of adverse events associated with long-term immunosuppression.

This preliminary analysis indicates that 80% of the patients in group B remained steroid-free 1 year postoperatively, with lower tacrolimus trough levels and no difference in other adverse events.

Histological grade of hepatocellular carcinoma (HCC) is an important prognostic factor affecting patient survival after orthotopic liver transplantation (OLT).Design: Retrospective analysis.Setting: University-based teaching hospital.Patients: Of 952 OLTs performed between June 1991 and January 1999, 56 OLT recipients had histologically proven HCC in the explant liver. Of those, 53 patients with complete clinicopathologic data were analyzed. A single pathologist blinded to the outcome of each patient reviewed all histological specimens.Results: Median follow-up was 709 days. Overall survival for patients with tumors sized 5 cm or less at 1, 3, and 5 years was 87%, 78%, and 71%, respectively (Kaplan-Meier). Univariate analysis revealed the size, number, and distribution of tumors; the presence of microscopic vascular invasion and lymph node metastasis; histological differentiation; and pTNM stage to be statistically