Preliminary experience with alemtuzumab (Campath-1H) and low-dose tacrolimus immunosuppression in adult liver transplantation.

BACKGROUND: The administration of alemtuzumab (Campath-1H [C1H]; Berlex Laboratories, Montville, NJ) at transplantation prevents a vigorous immune response and is believed to allow a gradual engagement of the host immune system. We report our preliminary experience with C1H and tacrolimus (Tac) immunosuppression in adult liver transplantation. METHODS: We administered C1H and low-dose Tac to 40 adult recipients of cadaveric liver allografts between December 2001 and April 2003. A control group who met the same eligibility criteria consisted of 50 liver transplant recipients treated with our standard Tac and steroids protocol. RESULTS: Baseline characteristics and patient and graft survival were similar (P >0.15). The incidence of acute rejection was significantly lower during the first 2 months posttransplantation (P =0.002) and slightly lower overall in the study group versus the control group at 12 months (46% vs. 55%, P =0.12, log-rank test). Median time to rejection among those experiencing rejection was significantly longer in the study group versus control group (2.76 vs. 0.34 months, P =0.0007). The mean Tac dose, 12-hr trough level, and percentage of patients receiving maintenance steroids were significantly lower in the group receiving C1H and Tac (P <0.0001 during the first 3 months, P <0.05 thereafter), as were the mean creatinine levels (P <0.05) and incidence of nephrotoxicity (P =0.004, conversion from Tac to other agents). Finally, in the group receiving C1H/Tac, patients with an average Tac trough level less than 6.5 ng/mL during the first 2 months post-transplantation demonstrated a significantly higher rejection rate beyond that time (P =0.02). CONCLUSION: C1H and low-dose Tac seems to be at least as effective as our standard Tac and steroids regimen in preventing acute rejection in adult liver allotransplantation with less renal toxicity and less use of maintenance steroids.

Partial abdominal evisceration, ex vivo resection, and intestinal autotransplantation for the treatment of pathologic lesions of the root of the mesentery.

BACKGROUND: Resection of lesions of the root of the mesentery with established techniques is difficult and at times impossible because of their proximity to the blood supply of the intestine. Damage of the superior mesenteric vessels necessitates resection of the intestine, resulting in short bowel syndrome and intestinal failure. STUDY DESIGN: We describe a surgical technique drawn from our experience in intestinal transplantation in which the root of the mesentery (including the lesion) and the head or the entire pancreas, duodenum, small intestine, and part of the colon are excised en bloc and preserved in a cold solution. Resection of the lesion is performed in a bloodless field ex vivo, and the salvaged intestine is reimplanted in the abdominal cavity. We performed this procedure in four patients, two adult and two pediatric, who had extensive neoplasms of the root of the mesentery. Their underlying diseases were mesenteric fibroma, vascular dysplasia of the root of the mesentery, pancreatic cancer, and desmoid tumor. RESULTS: Local control of the lesions was achieved in all four cases, preserving at the same time enough small intestine to avoid short bowel syndrome. All patients survived the operation and live on enteral nutrition 6 to 49.5 months after the procedure. CONCLUSIONS: The procedure of partial abdominal exenteration, ex vivo resection, and autotransplantation is an extension of our experience with intestinal transplantation. In selected cases, this technique may be useful in the treatment of extensive, otherwise unresectable lesions of the root of the mesentery.

Alemtuzumab (Campath-1H) combined with tacrolimus in intestinal and multivisceral transplantation.

BACKGROUND: We combined alemtuzumab (Campath-1H, Berlex Laboratories, Montville, NJ) and tacrolimus (Tac) immunosuppression for intestinal and multivisceral transplantation. MATERIALS AND METHODS: A total of 21 adult patients received 24 grafts: 14 intestinal, nine multivisceral, and one liver-intestinal graft. Alemtuzumab was administered perioperatively in four doses with low-dose Tac (levels 10-15 ng/dL) and no maintenance steroids. Tac was substituted with sirolimus in case of Tac-related complications. Suspected or mild rejections were treated with steroids. Moderate rejections were treated with steroids or OKT3. Severe rejections were treated with OKT3. RESULTS: Of the 16 patients that were followed up for an average of 9 months, 12 are alive with functioning grafts. Two patients experienced severe rejection, three experienced moderate rejection episodes, and seven experienced mild acute rejection episodes. Four patients never developed acute rejection. Infectious complications included a cytomegalovirus enteritis and four fungal infections (related to central venous access). CONCLUSIONS: The combination of alemtuzumab and Tac therapy without steroid use seems to efficiently prevent acute rejection in a significant number of patients without causing frequent opportunistic infections.

Expression of MUC2 and MUC4 proteins and cytokines: early markers of intestinal graft rejection.

BACKGROUND: Histopathologic examination (HP) is the primary method of monitoring intestinal graft rejection. Alterations in mucin levels have been demonstrated in bowel diseases. The aim of this study was to detect early markers of intestinal graft rejection based on mucin and cytokine levels. METHODS: Allogeneic and syngeneic orthotopic intestinal transplantations were performed in untreated Lewis strain recipient rats from Dark Agouti and Lewis strain donors, respectively (unmodified rejection and nonrejection groups). Similarly, allogeneic and syngeneic orthotopic intestinal transplantations were performed in tacrolimus (immunosuppression)-treated groups. HP was performed on hematoxylin-eosin and periodic acid Schiff-stained sections. Expression of MUC2 and MUC4 proteins and of mRNA was detected by immunohistochemistry and Northern analysis, respectively. Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and transforming growth factor-beta(1) were measured by reverse transcription-polymerase chain reaction. RESULTS: HP revealed early or mild rejection on day 3, moderate rejection on day 5, and severe rejection on day 7 posttransplantation (posttx) in the unmodified rejection group. A significant (P<0.01) increase in MUC2 and MUC4 expression was observed on day 3 posttx in the allogeneic rejection group compared with syngeneic controls; the levels decreased by day 7. Goblet cells were significantly more frequent on day 3 compared with days 5 and 7 posttx (P<0.01). IFN-gamma and TNF-alpha expression were also higher in the rejection group. CONCLUSIONS: Early transplant rejection is associated with increased MUC2, MUC4, IFN-gamma, and TNF-alpha expression. These markers combined with HP may assist in the diagnosis of early intestinal graft rejection.