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.     

Analysis of rejection episodes in over 100 pediatric intestinal transplant recipients

Rejection after intestinal transplant is a significant source of morbidity and mortality. We analyzed number of rejections, severity, and duration of episodes in pediatric recipients of intestinal transplants. One hundred eighteen intestinal transplants were performed: intestine (n = 27), liver-intestine (n = 27), modified multivisceral (n = 7), and multivisceral (n = 57). A total of 186 rejections were classified: mild (n = 89), moderate (n = 70), severe (n = 27). Duration of episodes doubled for each increasing step in severity. Treatment of mild rejection was with steroids, moderate rejection was treated with OKT3, severe rejection required OKT3 and organ removal. Most rejections occurred during the first month posttransplant, with the incidence of all rejections declining after 6 months posttransplant. Intestine and liver-intestine recipients had significantly higher probability of developing severe rejections, as compared to MVT. In summary, recipients of MVT seemed to be protected from rejection as compared to intestine or liver-intestine recipients.     

Intestinal Transplantation in Children: The First Successful Italian Series

The preliminary experience of the first Italian program of pediatric intestinal transplantation is presented herein. A multidisciplinary group with broad experience in pediatric solid organ transplantation started the program. Nine children with complications of chronic intestinal failure were listed for transplantation. One child died on the waiting list; one received an isolated liver transplantation; three isolated intestinal; three multivisceral; and one, a combined liver/intestine transplantation. There was no in-hospital mortality, and all children were weaned from parenteral nutrition. The recipient of the multivisceral graft died after 14 months for unknown causes. All other recipients are alive after a median follow-up of 13 months. Patient and graft actuarial survivals for recipients of intestinal grafts were 100% at 1 year and 75% at 2 years.     

Association of emergence of HLA antibody and acute rejection in intestinal transplant recipients: a possible evidence of acute humoral sensitization

Development of HLA antibody has been associated with chronic allograft failure in kidney recipients. We tested HLA antibody in posttransplant sera of intestinal recipients: 126 sera from 28 pediatric recipients were tested for HLA antibody by flow PRA (f-PRA). Median age was 1.1 years (0.44-17). Graft types included isolated intestine (n = 6), liver and intestine (n = 3), modified multivisceral (n = 3), and multivisceral grafts (n = 16). Greater than 10% of either class I (CI) or class II (CII) f-PRA was considered positive, and >30% strongly positive. Five of 28 patients had positive f-PRA in multiple samples; the remaining 23 had either no positive or only one positive sample. Three patients had strongly positive f-PRA. Patients with multiple positive samples were recipients of two modified multivisceral and three multivisceral grafts. Only one of these patients had a positive PRA pretransplant. Cytotoxic cross-match at transplant was negative for all. The three with strongly positive f-PRA showed significant episodes of rejection around the time of positive samples. One of them who persistently had f-PRA value >80% (from day 13-113) died of refractory rejection. The other two had f-PRA of 76% and 53% during the early postoperative course with associated episodes of rejection. F-PRA value decreased with rejection therapy. Only one of the 23 patients (4%) with negative f-PRA had an episode of rejection around the time of sample collection. Development of HLA antibody after intestinal transplantation seems to have significant association with acute rejection episodes.     

Initiation of an intestinal transplant program: the Indiana experience

INTRODUCTION: Establishment of a new intestinal transplant (Itx) program in the United States entails significant programmatic costs and a steep learning curve. We report results of the first 4 years of the program at Indiana University. METHODS: Forty-six intestinal and multivisceral transplants (MVtx) were performed between 2003 and 2007. All organ procurements were performed by our team. Immunosuppression included an induction protocol combined with maintenance tacrolimus monotherapy. Scheduled rejection surveillance was with magnification endoscopy. RESULTS: Forty-three patients (13 children and 30 adults) received 10 Itx (22%), 5 modified MVtxs (11%), and 31 (MVtx, 67%). Recipient ages ranged from 3 months to 66 years, with median follow-up time of 15 months. Thirty-five patients are currently alive (81%). Patient and graft survival at 30 days was 85%/86% in pediatric and 93%/91% in adult; overall survival was 69%/64% in pediatric and 87%/75% in adult. Thirty patients (69%) experienced episodes of rejection. Multivisceral transplanted patients experienced less episodes of severe rejection (2/31, 6%) when compared with patients with isolated Itx and modified MVtxs. Retransplantation was performed in three patients with nonresponsive severe acute rejection. CONCLUSION: The Indiana University Intestinal and Multivisceral Transplant program experienced significant early graft loss and mortality among pediatric patients, but not among adults. This discrepancy resolved within 2 years of program initiation. After 4 years, adult and pediatric graft and patient survival statistics are similar to those at other programs.     

Italian experience in adult clinical intestinal and multivisceral transplantation: 6 years later

PATIENTS AND METHODS: Between December 2000 and November 2006, 28 isolated intestinal transplants and nine multivisceral transplants (five with liver) from cadaveric donors have been performed for short gut syndrome (n = 15), chronic intestinal pseudo-obstruction (n = 10), Gardner's syndrome (n = 9), radiation enteritis (n = 1), intestinal atresia (n = 1), and massive intestinal angiomatosis (n = 1). Indications for transplantations were: loss of venous access, recurrent sepsis due to central line infection, and/or major electrolyte and fluid imbalance. Liver dysfunction was present in 19 cases. All patients were adults of median age at transplant of 34.7 years and mean weight 59.6 kg. All recipients were on total parenteral nutrition for a mean time of 38.8 months. Mean donor/recipient body weight ratio was 1.1. RESULTS: The mean follow-up was 892 +/- 699 days. Twenty-five patients were alive (67.5%) with 3-year patient survivals of 70% for isolated intestinal transplantations and 41% for the multivisceral transplantations (P = .01). The mortality rate was 32.5% with losses due to sepsis (63%) or rejection. Our 3-year graft survival rates were 70% for isolated intestinal transplantations and 41% for multivisceral transplantations (P = .02); graftectomy rate was 16%. These were 88% of grafts working properly with patients on regular diet with no need for parenteral nutrition. DISCUSSION AND CONCLUSIONS: Induction therapy has reduced the doses of postoperative immunosuppressive agents, especially in the first period, lowering the risk of renal failure and sepsis, mucosal surveillance protocol for early detection of rejection dramatically reduced the number of severe acute chronic rejections.     

Outcome analysis of 71 clinical intestinal transplantations.

OBJECTIVE: The aim of the study was to determine risk factors associated with graft failure and mortality after transplantation of the intestine alone or as part of an organ complex. SUMMARY BACKGROUND DATA: Even with modern immunosuppressive therapies, clinical intestinal transplantation remains a difficult and unreliable procedure. Causes for this and solutions are needed. METHODS: Between May 1990 and February 1995, 71 intestinal transplantations were performed in 66 patients using tacrolimus and low-dose steroids. The first 63 patients, all but one treated 1 to 5 years ago, received either isolated grafts (n = 22), liver and intestinal grafts (n = 30), or multivisceral grafts (n = 11). Three more recipients of allografts who recently underwent surgery and one undergoing retransplantation were given unaltered donor bone marrow cells perioperatively as a biologic adjuvant. RESULTS: Of the first 63 recipients, 32 are alive: 28 have functioning primary grafts and 4 have resumed total parenteral nutrition after graft enterectomy. Thirty-five primary grafts were lost to technical and management errors (n = 10), rejection (n = 6), and infection (n = 19). Regression analysis revealed that duration of surgery, positive donor cytomegalovirus (CMV) serology, inclusion of graft colon, OKT3 use, steroid recycle, and high tacrolimus blood levels contributed to graft loss. All four intestine and bone marrow recipients are alive for 2-3 months without evidence of graft-versus-host disease. CONCLUSION: To improve outcome after intestinal transplantation with previous management protocols, it will be necessary to avoid predictably difficult patients, CMV seropositive donors, and inclusion of the graft colon. Bone marrow transplantation may further improve outcome by ameliorating the biologic barriers of rejection and infection and allowing less restrictive selection criteria.     

Anti-TNF-alpha therapy for acute rejection in intestinal transplantation

INTRODUCTION: We present our experience with infliximab rescue therapy for steroid- and OKT3-resistant rejection after intestinal transplantation (ITx). METHODS: Twelve ITx and one multivisceral transplant recipients were immunosuppressed with tacrolimus, rapamycin, daclizumab, steroids (n = 10) or tacrolimus, campath, and steroids (n = 3). RESULTS: In two patients, severe acute rejection did not resolve despite steroid bolus therapy plus 5 to 10 days of OKT3 treatment. Signs of moderate rejection persisted in the distal portions of the grafts. Treatment with infliximab, a chimeric anti-TNF-alpha antibody (four infusions of 3 mg/kg body weight), induced a complete remission of histological and clinical signs of rejection. Two further patients with steroid-resistant rejection received two courses of infliximab (3 mg/kg body weight) as antirejection therapy. All rejection episodes resolved completely. CONCLUSIONS: Infliximab effectively treats steroid and OKT3 resistant acute rejection episodes of intestinal transplantations.     

Analysis of Acute Cellular Rejection Episodes in Recipients of Primary Intestinal Transplantation: A Single Center, 11-Year Experience

Intestinal transplantation has evolved over the years with major improvements in patient and graft survival. Acute cellular rejection of the intestine, however, still remains one of the most challenging aspects of postoperative management. We analyzed retrospectively collected data from 209 recipients of primary intestinal grafts at our institution over the past 11 years. A total of 290 episodes of biopsy-proven rejection requiring clinical treatment were analyzed. Rejection episodes doubled in length, on average, with each increasing grade (mild, moderate, severe). We observed increased incidence of overall rejection and particularly severe rejection in recipients of isolated intestinal and liver-intestine grafts in comparison with multivisceral grafts. Two rejection history variables had a significant negative impact on graft survival: the occurrence of a severe rejection episode and a rejection episode lasting >or=21 days. The lower incidence rate of severe rejection in recipients of multivisceral grafts might be due to a combination of increased donor lymphatic tissue and larger load of donor-derived immune competent cells present in the graft. The development of more effective monitoring and treatment protocols to prevent the occurrence of severe and/or lengthy rejection episodes is of critical importance for intestinal graft survival.     

Induction immunosuppression with thymoglobulin and rituximab in intestinal and multivisceral transplantation

BACKGROUND: Induction immunosuppression is now a common practice after intestinal and multivisceral transplantation. We report our experience in 27 adult recipients who received rituximab and rabbit antithymocyte globulin (rATG) in combination as induction agents. MATERIAL AND METHODS: Twenty-seven adult patients received 29 intestinal transplants between July 2004 and March 2007. All patients received induction immunosuppression therapy with rATG, rituximab, and steroids. Tacrolimums and a steroid taper were used for maintenance therapy. Patient and graft survival, episodes of rejection as well as posttransplant lymphoproliferative disease (PTLD) and graft-versus-host disease were analyzed. RESULTS: One-year patient and graft survival was 81% and 76%, respectively. Thirteen patients (48%) experienced 19 episodes of acute rejection (9 mild episodes, 2 moderate, and 8 severe). Patients with a multivisceral graft experienced less episodes of severe acute rejection (1 of 19, 5%) when compared with isolated intestinal transplants and modified multivisceral transplants (7 of 10, 70%). Two patients had episodes of skin graft-versus-host disease that responded to steroid boluses. PTLD was not seen in our series. Two patients developed cytomegalovirus enteritis. CONCLUSIONS: The combination of rATG and rituximab was an effective induction therapy in our preliminary data. The number and severity of rejection episodes increased when the liver was not included as part of the graft. An immunosuppression regimen including rATG, rituximab, and steroids may have a protective effect against PTLD and chronic rejection.     

Abdominal Wall Transplantation: Surgical and Immunologic Aspects

Abdominal wall transplantation is a type of composite tissue allograft that can be utilized to reconstitute the abdominal domain of patients undergoing intestinal transplantation. We have presented herein combined experience and long-term follow-up results of a series of abdominal wall transplants performed at 2 institutions. A total of 15 abdominal wall transplants from cadaveric donors were performed in 14 patients at the end of intestinal transplant surgery or, in 2 cases, a few days after the primary intestinal transplant. The vascular supply was through the inferior epigastric vessels, from the iliac vessels in 12 cases and via a microsurgical technique in 3 cases. Immunosuppression consisted of induction with alemtuzumab and maintenance treatment with tacrolimus monotherapy. Two grafts lost to vascular thrombosis were removed. Five patients are still alive, although all deaths were unrelated to the abdominal wall transplant. There were 3 episodes of abdominal wall graft rejection, treated with steroids; the abdominal wall graft and the intestinal grafts experienced rejection independent from each other. In summary, abdominal wall transplantation is a feasible technique for recipients of intestinal or multivisceral transplants, when the closure of the abdominal cavity by primary intention is technically impossible.     

Rejection episodes and 3-year graft survival under sirolimus and tacrolimus treatment after adult intestinal transplantation

PURPOSE: Mammalian target of rapamycin (mTOR) inhibitors have been recently introduced in clinical practice after intestinal transplantation. We focused on Sirolimus (Rapamycin) to examine effects on rejection and graft survival following intestinal transplantation. PATIENTS AND METHODS: Twenty isolated intestinal recipients and 5 multivisceral patients (2 with liver) in our series were divided into 3 groups: patients started on Sirolimus (because of nephrotoxicity or biopsy-proven rejection), who continued therapy longer than 3 months (n = 11); patients started on Sirolimus (because of nephrotoxicity or biopsy-proven rejection), who received therapy less than 3 months because of side effects (n = 4); and a control group, who never received rapamycin (n = 10). RESULTS: During prolonged treatment combined with Tacrolimus (Prograf), both Sirolimus groups showed a decreased number of acute cellular rejections (P < .01). Cumulative 3-year graft and patient survival rates were 81% in the Sirolimus greater than 3 months group, 100% in the Sirolimus less than 3 months group, and 80% and 90% in the control group, respectively (P = .63 and P = .62). CONCLUSION: In our experience, the use of mTOR-inhibitors in combination with calcineurin-inhibitors seemed to be more effective than monotherapy to reduce the number of rejections. Side effects can limit its use as maintenance therapy.     

Fine-needle aspiration biopsy allows early detection of acute rejection in children after renal transplantation

analysis detected rejections often before clinical signs. Half of the patients had increased serum creatinine concentration and 38% had fever at the time of rejection diagnosis. Both signs were present in only 19% of the episodes. A decrease in urine output (>20%) was seen in a third of the episodes. The rejections responded well to oral methylprednisolone (3 mg/kg/day), and lymphoglobulins were needed in only 12% of the episodes. More than 90% of the rejections were completely reversible and no transplant was lost because of acute rejection. CONCLUSION: The results indicate that FNAB is a safe and sensitive method for the diagnosis and follow-up of acute cellular rejection in pediatric recipients of different ages.     

Transplantation for the treatment of intra-abdominal fibromatosis

MATERIALS AND METHODS: During the last 9 years we treated 14 patients with a diagnosis of intra-abdominal fibromatosis. The 11 patients who received an intestinal allograft included isolated intestine (n = 6), liver-intestine (n = 1), intestine-kidney (n = 1), multivisceral (n = 1), multivisceral-kidney (n = 1), multivisceral-no liver (n = 1). Three patients received an intestinal autograft after partial abdominal evisceration and ex vivo tumor resection. Three patients additionally underwent an abdominal wall allograft. RESULTS: At follow-up until August 2004, all autotransplant patients are alive. Four intestinal transplant patients died within the first postoperative month. There were three graft losses. A patient who lost his graft early postoperatively was retransplanted but died of sepsis shortly there after. Two more patients lost their graft due to severe rejection and were retransplanted successfully. Two patients developed desmoid tumor recurrence in their abdominal or thoracic wall. Ten patients are alive 1 to 9 years posttransplantation. Nine have fully functioning grafts and one patient requires TPN supplementation at night due to dysmotility of her autograft. CONCLUSION: Intestinal allo-, or autotransplantation combined with transplantation of the abdominal wall can be lifesaving for patients suffering from extensive intra-abdominal fibromatosis.     

Daclizumab and Alemtuzumab as Induction Agents in Adult Intestinal and Multivisceral Transplantation: Rejection and Infection Rates in 40 Recipients During the Early Postoperative Period

Background

Allograft rejection in intestinal transplantation occurs frequently, and bacterial, fungal, and viral infections related to strong immunosuppression regimens remain an important complication posttransplantation. Induction therapy has enabled improvement in graft and patient survival rates.

Objectives

In analyze the effects of daclizumab and alemtuzumab as induction therapies on inflections complications and incidence of acute cellular rejection (ACR) during the early posttransplantation period.

Patients and Methods

Between December 2000 and August 2009, we performed 43 intestinal transplantation procedures in 42 adult recipients (median [SD] age, 34.8 [9.5] years; male-female ratio, 22:20; isolated or multivisceral graft, 32/11), and compared findings during the first 30 days posttransplantation in 40 recipients. Patients were divided into 2 groups: 12 treated with daclizumab (Zenapax; Hoffman-La Roche Ltd, Basel, Switzerland): 8 isolated intestinal grafts and 4 multivisceral grafts) and 28 treated with alemtuzumab (Campath-1H: 22 isolated intestinal grafts and 6 multivisceral grafts). Maintenance immunosuppression was based on tacrolimus and steroids in the first group and low-dose tacrolimus in the second group.

Results

During the first month posttransplantation, 8 daclizumab recipients (66.6%) experienced 9 episodes of mild ACR, which were successfully treated with steroid therapy, and 8 patients (66.6%) developed a bacterial infection requiring treatment. Fourteen episodes of ACR occurred in 12 alemtuzumab recipients (42.8%): 11 mild, 1 mild to moderate, and 2 moderate; 16 patients (57.1%) required treatment for infections. Five-year patient cumulative survival was 66% in daclizumab recipients and 43% in alemtuzumab recipients. Five-year graft survivals was 66% in daclizumab recipients and 41% in alemtuzumab recipients. In both groups, P was not statistically significative.

Conclusions

The infection rate is considerably high with both protocols. Alemtuzumab seems to offer better immunosuppression against ACRs during the first month posttransplantation.     

Liver transplantation across ABO blood groups in children

Late results after ABOI LTx are inferior to ABO compatible organs. We report seven patients who received LTx across ABO group for emergency indications. The blood type combinations were: A to O in three, B to O in two, and B to A in two. Episodes of acute and chronic rejection, immunosuppression, and biochemical and functional tests after transplantation as well as patient and graft survival were compared between ABOI group and patients with compatible ABO group transplanted due to FLF (group I) or in an elective setting (group II). Four children are alive. Two children died of sepsis and CNS damage or MOF, and one patient died during transplantation because of cardiac failure. All recipients of ABOI grafts received immunosuppression with cyclosporine or tacrolimus and steroids. MMF was added in two subjects, and induction with antilymphocyte globulins used in five patients. An acute rejection episode was diagnosed in two recipients between 7 and 11 days after LTx. All four living patients with ABOI grafts are doing well with follow-up time between 11 months and 5 years. In one patient PTLD occurred at 1 year after ABOI LTx but was cured by discontinuation of immunosuppression and administration of rituximab. Graft survival in the ABOI group was 57.1% versus 71% in group I and 73% in group II. Respective patients survival was 57.1% 71%, and 82.0% respectively. In conclusion, in urgent cases ABOI transplantation is justified in pediatric patients when compatible grafts are not available.     

Role of splenectomy in renal transplantation

One hundred sixteen renal transplants in 99 patients were reviewed. Patients were divided into four groups: 53 live donor recipients with pretransplant splenectomy, 13 nonsplenectomized live donor recipients, 20 cadaver recipients with splenectomy, and 30 nonsplenectomized cadaver recipients. Nonsplenectomized live donor recipients had fewer rejection episodes per month of graft function (p < 0.005). Serum creatinine in functioning grafts showed no differences between splenectomized and nonsplenectomized patients. In 73 splenectomized patients there were 14 related septic and/or thromboembolic complications, 6 fatal. Mean daily azathioprine dosage was greater in splenectomized patients (p < 0.005). There were no hyperacute rejections of second transplants in splenectomized patients, while 2 occurred in 8 nonsplenectomized patients. Splenectomy prior to renal transplantation did not decrease the number of rejection episodes per month of graft function and was associated with a higher rate of septic and thromboembolic complications.     

Transplantation of the spleen: effect of splenic allograft in human multivisceral transplantation

OBJECTIVES: To describe the effect of the splenic allograft in human multivisceral transplantation. SUMMARY BACKGROUND DATA: We performed transplants of the spleen as part of a multivisceral graft in an attempt to decrease both the risk of infection from an asplenic state and the risk of rejection by a possible tolerogenic effect. To our knowledge, this is the first report of human splenic transplantation in a large series. METHODS: All primary multivisceral recipients who received a donor spleen (N = 60) were compared with those who did not receive a spleen (N = 81). RESULTS: Thirty-five of 60 (58%) are alive in the spleen group, and 39 of 81 (48%) are alive in control group (P = 0.98). In univariate analysis, splenic recipients showed superiority in freedom-from-any rejection (P = 0.02) and freedom-from-moderate or severe rejection (P = 0.007). No significant differences were observed in analyses of infectious complications between the spleen and control groups. Both platelet and leukocyte counts became normal in splenic patients, whereas these counts were significantly increased in nonsplenic recipients. Observed incidence of graft versus host disease (GVHD) was 8.25% (5 of 60) in the spleen group and 6.2% (5 of 81) in the control group (P = 0.70). Increased incidence of autoimmune hemolysis was observed in the spleen group. CONCLUSIONS: Allograft spleen can be transplanted within a multivisceral graft without significantly increasing the risk of GVHD. The allogenic spleen seems to show a protective effect on small bowel rejection. Further investigation with longitudinal follow-up is required to precisely determine the immunologic and hematologic effects of the allograft spleen.     

Twenty-seven consecutive intestinal and multivisceral transplants in adult patients: a 4-year clinical experience

Adult isolated intestinal and multivisceral transplantation is gaining acceptance as the standard treatment for patients with intestinal failure with life-threatening parenteral nutrition-related complications. We report our 4-year experience with intestinal and multivisceral transplantation. We performed 20 isolated small bowel and seven multivisceral ones, including three with liver. The underlying diseases were mainly short bowel syndrome due to intestinal infarction, chronic intestinal pseudo-obstruction, and Gardner syndrome. Indications for transplant were loss of central venous access in 14 patients, recurrent sepsis in eight patients, and major electrolyte and fluid imbalance in five patients. One-year patient actuarial survival rate was 94% for isolated intestinal transplants and 42% for multivisceral recipients (P = .003), while 1-year graft actuarial survival rate was 88.4% for isolated small bowel patients and 42.8% for multivisceral ones (P = .01). The death rate was 18.5%. Our graftectomy rate was 14.8%. Our immunosuppressive protocols were based on induction agents such as alemtuzumab, daclizumab, and antithymocyte globulins. The majority of our complications were bacterial infections, followed by rejections and relaparotomies; most rejection episodes were treated with steroid boluses and tapering. We believe that our results were due to optimal candidate and donor selection, short ischemia time, and use of induction therapy. Multivisceral transplantation is a more complex procedure with less frequent clinical indications than isolated small bowel transplant, but our data concerning multivisceral transplants include only a small number of patients and require further evaluation.     

Intestinal transplantation in composite visceral grafts or alone.

Under FK 506-based immunosuppression, the entire cadaver small bowel except for a few proximal and distal centimeters was translated to 17 randomly matched patients, of whom two had antigraft cytotoxic antibodies (positive cross-match). Eight patients received the intestine only, eight had intestine in continuity with the liver, and one received a full multivisceral graft that included the liver, stomach, and pancreas. One liver-intestine recipient died after an intestinal anastomotic leak, sepsis, and graft-versus-host disease. The other 16 patients are alive after 1 to 23 months, in one case after chronic rejection, graft removal, and retransplantation. Twelve of the patients have been liberated from total parenteral nutrition, including all whose transplantation was 2 months or longer ago. The grafts have supported good nutrition, and in children, have allowed growth and weight gain. Management of these patients has been difficult and often complicated, but the end result has been satisfactory in most cases, justifying further clinical trials. The convalescence of the eight patients receiving intestine only has been faster and more trouble free than after liver-intestine or multivisceral transplantation, with no greater difficulty in the control of rejection.