Steroid-free liver transplantation using rabbit antithymocyte globulin and early tacrolimus monotherapy

BACKGROUND: In 2001, we published early results of a prospective randomized trial of 71 patients who received either steroids or rabbit antithymocyte globulin (RATG) for orthotopic liver transplantation (OLT). We now report follow-up on these patients and additional patients undergoing steroid-free OLT. METHODS: A total of 119 adult OLT recipients were prospectively randomized to receive either methylprednisolone 1,000 mg followed by a 3-month steroid taper or a steroid-free regimen of RATG 1.5 mg/kg during the anhepatic phase followed by a 1.5 mg/kg dose on posttransplant day 1. Maintenance immunosuppression consisted of tacrolimus and mycophenolate mofetil in both groups. Mycophenolate mofetil was weaned over 3 months in the first 71 patients and over 2 weeks in the last 48 patients, achieving tacrolimus monotherapy by 2 weeks posttransplant. Subsequently, a group of 24 sequential OLT recipients received the steroid-free (RATG) protocol. Endpoints of the study were survival, rejection, infectious complications, posttransplant diabetes, and recurrent hepatitis C virus. RESULTS: One-year patient survival was 85% in each group of the prospective randomized trial with a mean follow-up of 18.5 months. One-year graft survival was 82% in the RATG group and 80% in the steroid group (P=not significant). Patient and graft survival of the 24 nonrandomized RATG patients was 96% with a mean follow-up of 3 months. The incidence of rejection was not significantly different; however, 50% of the patients in the steroid group required pulse steroids to reverse the rejection compared with only one patient (1.6%) in the RATG group (P=.03). The incidence of cytomegalovirus infection (P<.05) and posttransplant diabetes was higher in the steroid group (P=.03). There was a trend toward decreased severity of hepatitis C virus in the RATG group. CONCLUSIONS: Steroid-free liver transplantation using RATG and early tacrolimus monotherapy effectively reduces immunosuppression-related complications with excellent survival.     

Alemtuzumab induction with tacrolimus monotherapy in de novo renal transplantation

OBJECTIVES: Alemtuzumab is increasingly being used as induction therapy for kidney transplantation, allowing immunosuppression minimization. This study examined the efficacy of alemtuzumab induction followed by low-dose tacrolimus monotherapy in standard risk primary kidney transplant patients. METHODS: This retrospective cohort of primary standard risk renal transplant recipients were given alemtuzumab induction and low-dose tacrolimus maintenance immunosuppression (target trough 7 to 10 ng/mL for the first 6 months and 5 to 7 ng/mL thereafter). Serum creatinine values, acute rejection episodes, and graft survival were noted at week 1 as well as months 3, 6, 12, and 18. RESULTS: At the time of analysis, 47 patients were at 6 months, 28 at 12 months, and 6 patients at 18 months from transplant. Mean follow-up was 12.53 months (range, 6 to 23). Mean serum creatinine was 1.47 +/- 0.65 mg/dL at 3 months, 1.56 +/- 0.84 at 6 months, 1.45 +/- 0.37 at 12 months, and 1.74 +/- 0.35 at 18 months. The 1-year clinical acute rejection rate was 21% (6/28), occurring at 0 to 3 months in 2 (33%), 4 to 6 months in 1 (17%), and >6 months in 3 patients (50%). Biopsy-proven acute rejection was 14% (4/28). The episodes were classified as borderline in one, Banff 2A in two, and Banff 3 in one patients. One patient had both acute cellular and acute humoral rejection; half responded to steroid pulse therapy. The 1-year patient survival rate was 90%. The 1-year death-censored graft survival rate was 98%. CONCLUSION: Alemtuzumab induction with tacrolimus monotherapy is an acceptable option in standard risk patients. BPAR was 14%, but renal function remained satisfactory at 18 months posttransplant.     

Efficacy and safety of induction therapy with rabbit antithymocyte globulins in liver transplantation for hepatitis C

BACKGROUND: Hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is the leading cause for orthotopic liver transplantation (OLT). However, in recent years, the long-term results of OLT in this setting are worsening, possibly due to the powerful immunosuppressants in use. The aim of our study was to assess the safety and efficacy of induction therapy using rabbit antithymocyte globulin antibodies (RATG). METHODS: Over an 18-month period from January 2000 to June 2001, 16 patients underwent OLT for HCV-related ESLD and survived more than 1 month posttransplantation. They received induction therapy based on RATG (Thymoglobulins, Sangstat, France) at 1 mg/kg per day for 3 consecutive days, and it was then adjusted to maintain a CD2 count below 50/mm(3). Overall, RATG was given for a median of 5 days for a total dose of 406 +/- 45 mg. Steroids were started pretransplant and tacrolimus on day 1. The primary end-points were patient and graft survivals at 6 months posttransplantation, incidence of rejection, infectious complications (bacterial, viral, and fungal) and recurrence of HCV infection based on biochemical, virological, and histologic criteria. RESULTS: The survival rates were 100% for patients and 93.7% for grafts. The acute rejection rate was 37.5%. The median time to acute rejection was 15.5 days. There was only one serum sickness case. Cytomegalovirus infections occurred in 25% of patients. The rate of de novo diabetes that required insulin therapy was at 50%. The rate of HCV recurrence was 56.25%. In addition, HCV RNA serum concentrations increased significantly posttransplantation (>1 log). In conclusion, RATG induction therapy is safe and efficient in HCV-positive liver recipients.     

Induction with rabbit antithymocyte globulin versus induction with corticosteroids in liver transplantation: impact on recurrent hepatitis C virus infection

This study compares the clinical course of recurrent hepatitis C virus (HCV) infection between 64 patients, who were randomized to receive either rabbit antithymocyte globulin (RATG) or steroids as induction therapy with tacrolimus for maintenance. The HCV recurrence was assessed by HCV RNA levels, peak ALT at 3-6 months, the grade of inflammation at biopsy at 3-6 months posttransplant, progression of fibrosis, and survival. All patients had also received antiviral therapy with interferon alpha 2b and ribavirin, if there were no contraindications. There was no statistically significant difference between the two groups in terms of inflammation at 3 months, peak ALT, or HCV RNA. The survival between the two groups of patients was similar. It appears that steroid-free liver transplantation with RATG induction does not have any negative influence on HCV recurrence in hepatitis C patients after liver transplantation.     

Powerful but limited immunosuppression for cardiac transplantation with cyclosporins and low-dose steroid

Cyclosporin and low-dose prednisone provide powerful but limited immunosuppression for orthotopic cardiac transplantation. Optimal long-term survival was possible only with rescue therapy using rabbit antithymocyte globulin (RATG) when myocyte necrosis could not be reversed with pulse steroid therapy. The continued absence of rejection following rescue therapy with RATG in six of the last 19 patients is responsible for the improved 79% cumulative survival rate at 9 months compared to the 61% cumulative survival rate at 1 year for the initial 23 patients. The difference is that among the latter group, seven patients had persistent histologic rejection with focal myocyte necrosis which was not reversed with pulse therapy of steroids (hydrocortisone) or an increased dose of maintenance prednisone (30 to 40 mg/day). Three of these seven died of acute rejection within 3 months and four died between 8 and 13 months. Consequently, the cumulative survival rate of these 23 patients at 2 years was 41%. The projected 2 year cumulative survival rate of the 19 patients should not decrease greatly, as new episodes of rejection have not occurred beyond 3 months in either group.     

Interleukin-2 receptor antibody (basiliximab) for immunosuppressive induction therapy after liver transplantation: a protocol with early elimination of steroids and reduction of tacrolimus dosage.

A prospective evaluation was performed to study the potential benefits of the use of interleukin-2 receptor antibody (IL-2Rab) in the induction therapy with early elimination of steroid and reduction of tacrolimus dosage in liver transplant recipients among whom 94% had chronic hepatitis B infection. Thirty-one liver transplant recipients who underwent right-lobe live donor (n = 19) or cadaveric (n = 12) liver transplantation received IL-2Rab, basiliximab 20 mg intravenously within 6 hours of graft reperfusion and on postoperative day 4 (IL-2ab group). Two doses of steroid injection were given intraoperatively and on postoperative day 1. Postoperative immunosuppression was maintained with oral tacrolimus and mycophenolate mofetil without the use of steroids. The operative outcomes were compared with those of 49 patients who received standard immunosuppressive regimen consisting of tacrolimus and corticosteroid (steroid group). The overall postoperative morbidity and hospital stay were comparable between the 2 groups. There were significantly lower incidences of postoperative new-onset diabetes (0% vs 28%, P =.011), acute cellular rejection (6% vs 27%, P =.038), and cytomegalovirus (CMV) antigenemia (0% vs 18%, P =.011) in the IL-2Rab group compared with the steroid group. The blood cholesterol level at 6 months after transplantation was significantly lower in the IL-2Rab group (median, 4.0 vs 4.4 mmol/L, P =.007). On follow-up, none of the patients in the IL-2Rab group had hepatitis B viral breakthrough or hepatocellular carcinoma (HCC) recurrence, whereas 1 and 3 patients in the steroid group developed these complications, respectively. In conclusion, treatment of liver transplant recipients with IL-2Rab with early withdrawal of steroids and reduction of tacrolimus dosage is associated with lower incidences of postoperative new-onset diabetes, acute cellular rejection, and CMV antigenemia, as well as a lower serum cholesterol level. Further studies and long-term follow-up are required to document their potential benefits on hepatitis B and HCC recurrences.     

Prospective randomized trial of steroid withdrawal in liver transplant patients: preliminary report

Abstract Although steroid withdrawal has been successfully performed in heart and kidney transplant recipients, no controlled studies of SW have been carried out in liver transplant patients. To evaluate this possibility a prospective controlled study was carried out in 46 liver transplant recipients operated on after may 1991. They all received a sequential quadruple immunosuppression consisting of 3 mg/kg antithymocyte globulins (RATG) for the first 5 postoperative days, cyclosporin A (starting from day 3–5 and maintaining parenteral whole-blood trough levels at 200–300 ng/ml during the first month and at 150–250 thereafter), azathioprine (1 mg/kg per day for the first month) and steroids. Prednisone was started at a dose of 200 mg per day 1 and then tapered to 20 mg/day over the first posteroperative week; this dose was maintained until day 90 when the patients were randomly allocated either to long-term steroid therapy (0.1 mg/kg per day) or to steroid withdrawal. Minimum follow-up after randomization was 6 months (6–27 months). Liver biochemistry was checked at regular intervals throughout the follow-up period. Liver biopsies were performed whenever clinically indicated and also in the first 19 patients during readmission for annual review. The incidence ot acute and chronic rejection 90 days from liver transplantation was 2.5% in patients maintained on long-term therapy. No patient in the steroid-withdrawal group had experienced either an acute or a chronic rejection episode so far. Steroid-related complications did not differ significantly between the two groups. The most recent interim analysis showed that steroid withdrawal is a safe undertaking in liver transplant recipients arid may be successfully accomplished in almost all patients.     

Lipid metabolism in renal transplant patients receiving tacrolimus/sirolimus combination therapy

INTRODUCTION: The administration of sirolimus has been reported to be associated with high serum cholesterol and high triglyceride values. In a large prospective, multicenter 6-month study in renal transplantation, basic parameters of lipid metabolism (total serum cholesterol and triglycerides) were systematically assessed in patients who received tacrolimus/mycophenolate mofetil/steroids (Tac/MMF), tacrolimus/0.5 mg sirolimus (SIR)/steroids (Tac/0.5SIR) on tacrolimus/2 mg sirolimus/steroids (Tac/2SIR). METHODS: For purposes of analysis, lipid parameters were classified using the National Kidney Foundation Dyslipidemia Classification definitions. RESULTS: Complete sets of data at all visits (baseline, months 1, 3, and 6) were available for 211 Tac/MMF, 210 Tac/0.5SIR, and 203 Tac/2SIR patients. Total serum cholesterol in the Tac/MMF group was 193.4 at baseline and 202.9 mg/dL at month 6. Values increased from 196 mg/dL to 212.5 mg/dL in Tac/0.5SIR and from 200 mg/dL to 230.5 mg/dL in Tac/2SIR. Differences in parameters between treatment groups were statistically significant (P < .05). Serum triglycerides decreased from baseline to 6 months in Tac/MMF, increased from 176.3 mg/dL (baseline) to 191.4 mg/dL (6 months) in Tac/0.5SIR and from 203 mg/dL to 255.3 mg/dL in Tac/2SIR. Parameters differed significantly between Tac/0.5SIR versus Tac/2SIR at P = .0069, and between Tac/MMF versus Tac/2SIR at P = .0013. In the Tac/2SIR group 36.5% had "high" serum cholesterol and 8.3% had "very high" triglyceride levels at 6 months. CONCLUSION: Total serum cholesterol levels were relatively stable and serum triglycerides decreased between baseline and month 6 using a Tac/MMF regimen. Contrastingly, the Tac/SIR combinations led to increased total cholesterol values (at both sirolimus dose levels) and Tac/2SIR also led to increased triglyceride levels.     

Induction therapy with either anti-CD25 monoclonal antibodies or rabbit antithymocyte globulins in liver transplantation for hepatitis C

BACKGROUND: Hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is the leading cause for orthotopic liver transplantation (OLT). The aim of our sequential study was to assess the safety and efficacy of induction therapy using either rabbit antithymocyte globulins (RATG) or anti-CD25 monoclonal antibodies. METHODS: From January 2000 to January 2003, 31 patients underwent OLT for HCV-related ESLD, and survived more than 1 month post-transplantation. Up to July 2001, induction relied on RATG (Thymoglobulins; Sangstat, Lyon, France) which was given for a median of 5 d, i.e. a total dose of 406 +/- 45 mg (n = 16; group I). Thereafter, induction was based on either basiliximab or dacluzimab (n = 15; group II). Steroids and tacrolimus (from day 1 onwards) were given as maintenance therapy. The primary end-points were at 6 months post-transplantation. RESULTS: Patient and graft survivals were excellent and similar in both groups. The acute rejection rate was 37.5% in group I and 20% in group II (p = ns). The rates of serious bacterial and fungal infections as well as cytomegalovirus infections were similar in both groups. Even if the overall pattern of post-transplant liver enzymes did not differ between the two groups, the rate of HCV recurrence tended to be higher in group II (80%) compared with group I (56.25%; p = ns) patients. Both induction therapies were clinically and biologically well tolerated. CONCLUSION: RATG induction therapy is as efficient and as safe as induction with anti-CD25 monoclonal antibodies.     

Long-term graft outcomes after steroid withdrawal in African American kidney transplant recipients receiving sirolimus and tacrolimus

BACKGROUND: We previously reported excellent short-term outcomes in African American kidney transplant patients receiving tacrolimus/sirolimus and withdrawn from corticosteroid therapy three months after transplantation. We now report the long-term outcomes of patients subjected to this protocol. METHODS: In all, 47 African American kidney transplant recipients were enrolled in an uncontrolled trial in which they were initially treated with sirolimus, tacrolimus, and corticosteroids, without antibody induction therapy. Eligible patients were withdrawn from prednisone between three and five months posttransplant, and followed for acute rejection and changes in renal function. Outcomes (group 1, n=32) were compared to those of patients deemed not to be candidates for steroid withdrawal (group 2, n=15). RESULTS: After a mean follow-up of 48.5 months, 13 of 32 patients (41%) in group 1 developed acute rejection; only 13 patients (41%) remain steroid-free. Nine of 13 rejection episodes were associated with noncompliance. Graft loss occurred in 8 of 32 patients (25%) in group 1 and in 5 of 15 patients (33%) in group 2 (P=NS). Serum creatinine rose from 1.4+/-0.41 to 2.45+/-1.7 mg/dL in group 1 (P=0.004) and from 2.1+/-0.45 to 2.62+/-1.2 mg/dL (P=NS) in group 2. Among 13 patients in group 1 who remain steroid-free, creatinine concentration has risen from 1.28+/-.0.37 prior to steroid withdrawal to 1.64+0.54 at last follow-up (P=0.027). CONCLUSIONS: Late noncompliance and/or rejection in African Americans withdrawn from steroids have a negative impact on long-term graft function and survival. Steroid withdrawal may be associated with long-term deterioration of renal function, even in the absence of overt acute rejection.     

Minimization of Immunosuppressive Therapy After Renal Transplantation: Results of a Randomized Controlled Trial

Modern immunosuppressive regimens reduce the acute rejection rate by combining a cornerstone immunosuppressant like tacrolimus or cyclosporine with adjunctive agents like corticosteroids, mycophenolate mofetil (MMF) or azathioprine, often associated with untoward side effects. A 6-month randomized study was conducted in 47 European centers. Triple therapy with tacrolimus (trough levels 5-15 ng/mL), corticosteroids (dosage 10 mg/day) and MMF (1 g/day) was administered for 3 months. From day 92, patients either continued with triple therapy (control, n = 277), or stopped steroids (n = 279), or stopped MMF (n = 277). Surrogate markers for long-term benefits were changes in lipid profiles and occurrence of hematological, gastrointestinal and infectious complications. The 6-month acute rejection incidence (biopsy-proven) was similar in all groups (17.0% vs. 15.1% vs. 14.8%, p = 0.744), although the incidence after month 3 was higher in the steroid stop group than in the two other groups. Mean reductions in total cholesterol (18.9 mg/dL [0.49 mmol/L]) and LDL-cholesterol (8.1 mg/dL [0.21 mmol/L]) between months 4 and 6 were greater in the steroid stop group (p < 0.001). Leukopenia (p = 0.0082), serious CMV infection (p = 0.024), anemia (p = NS) and diarrhea (p = NS) were less frequent in the MMF stop group. In a study population of immunologically low-risk patients' withdrawal of corticosteroids or MMF from a tacrolimus-based therapy at 3 months was feasible. A longer follow-up will be needed to confirm the expected advantages for the long-term outcome and to assess the long-term safety of this minimization of immunosuppressive therapy.     

Intestinal transplantation with alemtuzumab (Campath-1H) induction for adult patients

BACKGROUND: Alemtuzumab (Campath-1H [C1H]) is a humanized monoclonal antibody directed against the CD 52 antigen that is present on the surface of T cells, B cells, natural killer cells and monocytes. We studied its application in intestinal transplantation. METHODS: This is a retrospective review of adult patients who underwent intestinal transplantation between December 1994 and May 2005. Group 1: non-C1H group (n = 39); group 2: C1H group (n = 37). C1H was administered as an induction immunosuppression in four doses (0.3 mg/kg), or in two doses (30 mg/kg). Tacrolimus levels were maintained at low level (5-10 ng/dL). No maintenance steroids were given. RESULTS: One-year survival of group 1 and group 2 patients were 57% and 70%, respectively. This difference is not statistically significant. Of 37 patients in group 2, 21 are alive. The incidence of rejection was lower in group 2 (P < .005). Average current tacrolimus level is 6.97 +/- 3.98 ng/dL. Seventeen patients (81%) are steroid free, and 15 (71%) are maintained solely on tacrolimus. There was no graft versus host disease in group 2. CONCLUSIONS: Our preliminary data suggest that C1H can provide effective immunosuppression for intestinal transplantation. Incidence of rejection was less with this regimen using low maintenance tacrolimus and minimal steroids.     

Preferential allocation of marginal kidney allografts to elderly recipients combined with modified immunosuppression gives good results

BACKGROUND: There is an increasing tendency to allocate kidneys from marginal donors in older recipients. This combination optimizes the uses of an expanded donor pool but demands attention for the higher nephrotoxic sensitivity of the kidney and the increased immunosuppression vulnerability of the elderly recipients. We aimed to reduce these hazards by means of a calcineurin-free induction therapy followed by a maintenance regimen targeted to minimize/withdraw steroid. METHODS: Eighty-eight single (43%) or double (57%) transplant recipients (58.4+/-5.7 years) from 88 marginal donors (67+/-8.3 years) received monoclonal anti-IL-2 receptor antibodies, mycophenolate mofetil (MMF), and steroid. When serum creatinine was less than 2.6 mg/dL, tacrolimus was started and MMF was withdrawn when the tacrolimus trough level was above 15 ng/ml. Steroid was tapered to 5 mg at day 45 and then progressively reduced. RESULTS: Overall patient and graft survival at the first and fourth year were respectively 100 and 96%, and 98 and 79%. Acute rejection rate was 13.6% (12/88), creatinine clearance remained stable (48.2 ml/min at the sixth month, 50.9 ml/min at 48th month). At the first, second, third, and fourth years, 23, 69, 80, and 100% of recipients were off steroids. For those on steroids, mean dose was respectively 2.6 mg/day from month 12. No recipient re-assumed steroids CONCLUSIONS: In the "old-for-old" allocation, the calcineurin-inhibitor avoidance at induction and the steroid withdrawal/minimization during the tacrolimus-based maintenance regimen allow a low acute rejection rate, a stable renal function, and favorable recipient and graft outcomes.     

Steroid withdrawal at 3 months after kidney transplantation: a comparison of two tacrolimus-based regimens

The 6 month prospective, randomized study compared the steroid-sparing potential of two tacrolimus-based regimens after renal transplantation. A total of 489 patients were randomized (1:1) to receive tacrolimus/mycophenolate mofetil (MMF)/steroids (n = 243; group Tac/MMF/S) or tacrolimus/azathioprine/steroids (n = 246; group Tac/Aza/S). At 3 months, steroids were tapered off in 267 (54.6%) patients free from steroid-resistant acute rejection and with serum creatinine concentrations <160 micromol/l. The incidence of biopsy-confirmed acute rejection at month 3 was lower in group Tac/MMF/S compared with group Tac/Aza/S (18.1% vs. 26.0%,P = 0.035). Moreover, more patients in the Tac/MMF/S group met the criteria for steroid withdrawal than in the Tac/Aza/S group (60.5% vs. 48.8%; P < 0.01). The incidence of acute rejection during months 4-6 was low in all groups, both for patients on steroid-free dual therapy (Tac/MMF: 2.7%, Tac/Aza: 0.8%) and for patients who continued steroid maintenance therapy (Tac/MMF/S: 3.5%, Tac/Aza/S: 7.1%). Moreover, kidney function was well preserved in steroid-free patients with month 6 median serum creatinine levels of 119.5 micromol/l (Tac/MMF), and 115.1 micromol/l (Tac/Aza). For patients who continued to receive steroids, month 6 median creatinine levels were 130.5 micromol/l (Tac/MMF/S) and 132.8 micromol/l (Tac/Aza/S). The criteria for the selection of patients to discontinue steroids were adequate. Both tacrolimus-based regimens allowed the safe discontinuation of steroids in low-risk patients at month 3. The Tac/MMF combination was superior in the prevention of acute rejections and more patients met the chosen criteria for steroid withdrawal.     

Potential immunological advantage of intravenous mycophenolate mofetil with tacrolimus and steroids in primary deceased donor liver transplantation and live donor liver transplantation without antibody induction.

With the current immunosuppressive regimens, graft loss secondary to immunological reasons after successful liver transplantation is a rarity; acute rejections, however, do occur, with the majority of them being steroid-responsive. The aim of the present study is to examine the rate of acute rejection with tacrolimus, intravenous (IV) mycophenolate mofetil (MMF), and steroids in primary deceased donor liver transplant (DDLT) and live donor liver transplant (LDLT) recipients. During the year 2005, 130 patients (mean age: 54.9 +/- 10.8, males: 84, females: 46, 112 DDLT and 18 LDLT) received primary liver transplantation. They were followed up for the incidence of acute rejection in the first 12 months. Liver biopsies were performed as clinically indicated; protocol liver biopsies were never performed. A total of 127 liver biopsies were performed. Thirty-two had a rejection activity index (RAI) score of > or =3, of which 24 biopsies in 20 patients were not treated with a steroid bolus. Eight (6.1%) patients (mean RAI score: 5.1 +/- 1.4) received 750 to 1500 mg of methylprednisolone over 3 days. Out of these, 2 were noncompliant, 4 were off MMF, and 1 was on cyclosporine. All patients responded to steroid therapy. None of the patients required any antibody preparation. In conclusion, IV MMF with tacrolimus and steroids is useful and required antirejection therapy in 6.1% of liver transplant recipients.     

Tacrolimus (FK506) versus cyclosporine microemulsion (neoral) as maintenance immunosuppression therapy in kidney transplant recipients

The effects of the calcineurin inhibitors tacrolimus (FK506) and cyclosporine (Neoral) on graft survival, function, and metabolic profile were evaluated in 69 patients receiving Neoral (group 1) and 54 patients receiving FK506 (group 2) for maintenance immunosuppression following kidney transplantation. Recipient and donor demographics and induction therapy were comparable, except for a higher number of sensitized patients in group 2 (n = 13). Acute rejection timing, severity, and infection rates and types were similar in both groups. During hospitalization, at 6 months, and at 1 year following transplantation, no significant differences were noted between groups in fasting glucose, serum cholesterol levels, triglyceride levels, or need for insulin or antihypertensive therapy. Mean serum creatinine levels on discharge (1.42 mg/dL +/- 0.14 vs 1.68 mg/dL +/- 0.3), at 1 month (1.45 mg/dL +/- 0.1 vs 1.39 mg/dL +/- 0.11), 3 months (1.46 mg/dL +/- 0.09 vs 1.32 mg/dL +/- 0.14), and 1 year (1.29 mg/dL +/- 0.08 vs 1.19 mg/dL +/- 0.09), but not at 6 months (1.42 +/- 0.37 vs 1.10 +/- 0.07; P = .001), were comparable between groups. The 1-year patient and graft survival rates were 98.3% for group 1 and 94.5% for group 2. When evaluated for acute rejection, infection, and metabolic differences, we conclude that both tacrolimus and cyclosporine are effective and safe calcineurin inhibitors for short-term use in kidney transplantation. A similar study is proposed to evaluate the long-term effects of both agents.     

Tacrolimus rescue in liver transplant patients with refractory rejection or intolerance or malabsorption of cyclosporine. The US Multicenter FK506 Liver Study Group.

Tacrolimus is an effective immunosuppressant in the rescue of liver allograft patients in whom conventional immunosuppression failed. Efficacy and safety were examined in a multicenter trial of liver transplant recipients converted to tacrolimus because of rejection despite cyclosporine (CyA) therapy or intolerance to CyA. Six hundred seventy-seven patients were enrolled onto the study; 475 patients for rejection, 197 patients for intolerance, and 5 patients treated compassionately. The mean daily dose of tacrolimus was less in the intolerance (Int) patients throughout the study: 0.22 versus 0.17 mg/kg at 1 week and 0.14 versus 0.11 mg/kg at 24 months in rejection (Rej) and Int patients, respectively. Mean blood levels paralleled dosing in both groups, but were greater in the Rej patients (10.7 v 8.3 ng/mL at 18 months). Kaplan-Meier estimates of patient and graft survival were similar in the two groups. Patient survival rates were 80.1% and 81.5%, and graft survival rates were 72.7% and 73.9% at 24 months in the Rej and Int patients, respectively. Most adverse events occurred with a similar incidence in the two groups. Those with a 4% or greater incidence were fever, viral hepatitis, and pneumonia. The incidence of sepsis, gastrointestinal hemorrhage, kidney failure, and convulsion was greater in the Int group. The incidence of abnormal liver function test results, hyperglycemia, headache, and abnormal kidney function was greater in the Rej group. Mean liver function test results decreased with time postrescue in both groups. Mean serum creatinine level increased from baseline to 18 months postrescue in both groups (1.44 to 1.51 mg/dL for Int patients, 1.14 to 1.48 mg/dL for Rej patients). We conclude tacrolimus is safe and effective rescue in liver transplant recipients with rejection or CyA intolerance.     

A case of plasma cell-rich acute rejection 18 months after kidney transplantation successfully treated with steroid pulse therapy

Abstract:  A 45-yr-old Japanese male underwent living-related kidney transplantation in August 2005, and immunosuppression consisted of tacrolimus, mycophenolate mofetil, methylprednisolone, basiliximab, and rituximab 200 mg. Allograft function was good, and the protocol biopsy post-transplant day 11 showed no evidence of rejection. The serum creatinine (s-Cr) level was maintained at the 1.2 mg/dL for 18 months. On February 2007, the patient's s-Cr level had increased to 2.03 mg/dL, and an episode biopsy was performed. The biopsy specimen demonstrated moderate to severe tubulitis and moderate interstitial infiltration of plasma cells and lymphocytes. The inflammatory cell infiltrate consisted of >30% plasma cells. The histopathological findings were consistent with plasma cell-rich acute rejection (PCAR). The PCAR was treated by steroid pulse therapy, and his s-Cr level decreased to 1.58 mg/dL. A biopsy three months after the steroid pulse therapy showed no evidence of rejection. The patient's allograft function is currently stable, and s-Cr level is 1.7 mg/dL. This is a case of PACR, that was successfully treated with steroid pulse therapy alone.     

Predictive factors for anemia within the first year after orthotopic liver transplantation

We sought to determine the prevalence and predictive factors for posttransplant anemia within the first year after orthotopic liver transplant (OLT) among 97 consecutive patients. Anemia was defined at months 6 and 12 according to the WHO criteria, that is, a hemoglobin (Hb) level of <12 g/dL for women and <13 g/dL for men. Immunosuppression relied on tacrolimus and steroids, with or without mycophenolate mofetil. Anemia was present in 64.5%, 50%, and 52.8% of patients pre-OLT versus 6 and 12. Thirty-three percent (month 6) and 30.3% (month 12) of anemic patients received recombinant erythropoietin therapy. A multivariate analysis revealed that the independent predictive factors for anemia at month 6 were mean corpuscular volume (<85 fL) at day 7, daily steroid dosage (<0.3 mg/kg), serum creatinine (>130 mumol/L), and Hb level (<11 g/dL) at month 1. Independent predictive factors for anemia at month 12 were daily steroid dosage at month 1 (<0.3 mg/kg), hematocrit at month 1 (<33%), red blood cell count at month 6 (<3.75 T/L), daily dosage at month 1 of cyclosporine or tacrolimus, and etiology of end-stage liver disease other than alcohol abuse. We concluded that anemia was highly prevalent within the first year of post-OLT. This observation deserves further investigation and appropriate treatment.     

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.