Long-term survival, nutritional autonomy, and quality of life after intestinal and multivisceral transplantation.

OBJECTIVE: To assess long-term survival, graft function, and health-related quality of life (QOL) after visceral transplantation. BACKGROUND: Despite continual improvement in early survival, the long-term therapeutic efficacy of visceral transplantation has yet to be defined. METHODS: A prospective cross-sectional study was performed on 227 visceral allograft recipients who survived beyond the 5-year milestone. Clinical data were used to assess outcome including graft function and long-term survival predictors. The socioeconomic milestones and QOL measures were assessed by clinical evaluation, professional consultation, and validated QOL inventory. RESULTS: Of 376 recipients, 227 survived beyond 5 years, with conditional survival of 75% at 10 years and 61% at 15 years. With a mean follow-up of 10 ± 4 years, 177 (92 adults, 85 children) are alive, with 118 (67%) recipients 18 years or older. Nonfunctional social support and noninclusion of the liver in the visceral allograft are the most significant survival risk factors. Nutritional autonomy was achievable in 160 (90%) survivors, with current serum albumin level of 3.7 ± 0.5 gm/dL and body mass index of 25 ± 6 kg/m(2). Despite coexistence or development of neuropsychiatric disorders, most survivors were reintegrated to society with self-sustained socioeconomic status. In parallel, most of the psychological, emotional, and social QOL measures significantly (P < 0.05) improved after transplantation. Current morbidities with potential impact on global health included dysmotility (59%), hypertension (37%), osteoporosis (22%), and diabetes (11%), with significantly (P < 0.05) higher incidence among adult recipients. CONCLUSIONS: With new tactics to further improve long-term survival including social support measures, visceral transplantation has achieved excellent nutritional autonomy and good QOL.

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

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.

Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges.

OBJECTIVE: To assess the evolution of visceral transplantation in the milieu of surgical technical modifications, new immunosuppressive protocols, and other management strategies. SUMMARY BACKGROUND DATA: With the clinical feasibility of intestinal and multivisceral transplantation in 1990, multifaceted innovative tactics were required to improve outcome and increase procedural practicality. METHODS: Divided into 3 eras, 453 patients received 500 visceral transplants. The primary used immunosuppression was tacrolimus-steroid-only during Era I (5/90­5/94), adjunct induction with multiple drug therapy during Era II (1/95­6/01), and recipient pretreatment with tacrolimus monotherapy during Era III (7/01­11/08). During Era II/III, donor bone marrow was given (n = 79), intestine was ex vivo irradiated (n = 44), and Epstein-Barr-Virus (EBV)/cytomegalovirus (CMV) loads were monitored. RESULTS: Actuarial patient survival was 85% at 1-year, 61% at 5-years, 42% at 10-years, and 35% at 15-years with respective graft survival of 80%, 50%, 33%, and 29%. With a 10% retransplantation rate, second/third graft survival was 69% at 1-year and 47% at 5-years. The best outcome was with intestine-liver allografts. Era III rabbit antithymocyte globulin or alemtuzumab pretreatment-based strategy was associated with significant (P < 0.0001) improvement in outcome with 1- and 5-year patient survival of 92% and 70%. CONCLUSION: Survival has greatly improved over time as management strategies evolved. The current results clearly justify elevating the procedure level to that of other abdominal organs with the privilege to permanently reside in a respected place in the surgical armamentarium. Meanwhile, innovative tactics are still required to conquer long-term hazards of chronic rejection of liver-free allografts and infection of multivisceral recipients.

Pyridoxal-5'-phosphate deficiency after intestinal and multivisceral transplantation.

BACKGROUND: Successful intestinal transplantation is measured by the achievement of clinical nutritional autonomy (CNA). However, the ability of the graft to maintain normal micronutrient levels including vitamins has yet to be thoroughly evaluated. OBJECTIVE: After an initial clinical observation of isolated cases of pyridoxal-5'-phosphate (PLP) deficiency, this prospective study was designed to address the incidence of, risk factors for, and management of PLP deficiency in adult intestinal transplant recipients. DESIGN: Serum PLP and homocysteine concentrations were prospectively measured before and after transplantation at frequent intervals. RESULTS: PLP deficiency occurred in 10% of candidates and in 96% of recipients within a median onset of 30 d (range: 4-118 d) after transplantation. Of this group, 41% were receiving parenteral nutrition (PN), 41% were receiving enteral feeding, and the remaining 18% had already achieved CNA. The overall cumulative risk was 24% at 15 d, 59% at 30 d, 79% at 45 d, and 90% at 90 d; none of the risk factors, including homocysteine concentrations, were significant. Nonetheless, the development of PLP deficiency during PN therapy was associated with a significant (P < 0.001) delay in the achievement of CNA. Despite development of severe deficiency in most cases, none of the subjects experienced clinical manifestations of PLP deficiency because of prompt replacement therapy. CONCLUSIONS: Serial monitoring of serum PLP concentrations is recommended for PN-dependent patients with short-bowel syndrome before and after transplantation for early detection and prompt initiation of preemptive therapy. Long-term measurement at frequent intervals is also recommended, particularly for transplant recipients, to diagnose late deficiency despite achievement of CNA and to prevent toxicity from overdose.