BACKGROUND:

For cyclosporine (CsA), 2-hr postdose level (C2) is the best single time point predictor of the area under the curve and a critical measure for effective dosing. The therapeutic CsA microemulsion (Neoral) C2 range in de novo heart transplant patients remains to be determined.

PURPOSE:

The purpose of this study was to determine the efficacy of CsA C2 monitoring in de novo heart transplant patients receiving basiliximab induction.

METHODS:

This prospective, multicenter, randomized study enrolled 87 adult heart transplant recipients stratified according to 4 to 6 hrs posttransplant serum creatinine less than or equal to 170 micromol/L (cohort A) or more than 170 micromol/L (cohort B). Patients in cohort A were randomized into three C2 ranges (A1: "high" n=25, 1600-1800 ng/mL; A2: "intermediate" n=27, 1400-1600 ng/mL; and A3: "low" n=24, 1200-1400 ng/mL). Patients in cohort B were randomized into intermediate (n=5) and low C2 (n=6). Target ranges were progressively lowered after 1 month. Immunosuppression included basiliximab, Neoral, mycophenolate mofetil, and corticosteroids. Endpoints were acute rejection and renal function.

RESULTS:

The incidence of acute rejection at 12 months was 44% in group A1, 41% in group A2, 33% in group A3, and 27% in cohort B. Pretransplant and 12-month creatinine clearance (mL/min) were group A1, 72+/-25 and 64+/-24; group A2, 81+/-32 and 68+/-25; group A3, 91+/-28 and 86+/-26; and cohort B, 62+/-28 and 79+/-37.

CONCLUSION:

These results suggest that C2 monitoring is safe in de novo heart transplant patients. A low Neoral C2 range in combination with basiliximab induction resulted in preserved renal function without increased risk of acute rejection.

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Basiliximab is a monoclonal antibody that binds to the alpha subunit (CD(25)) of the interleukin-2 receptor of activated T lymphocytes. The advantage of basiliximab in organ transplantation is the reduce possibility to calcineurin inhibitor dosages to avoid nephrotoxicity. Basiliximab has significantly reduced the incidence of acute rejection (AR) in renal transplant recipients; however, the results are uncertain in liver transplantation (LT). The objective of this investigation was to assess the effect of basiliximab to prevent AR in the first 6 months after pediatric LT. From March 2000 to October 2001, 32 recipients of a primary orthotopic cadaveric or living donor LT were given basiliximab by intravenous bolus injection on the day of transplantation (day 0) and on day 4. Four children who received one dose were excluded from the study. The rate and the intensity of AR episodes, the incidence of chronic rejection, serum creatinine level, incidence of infections, adverse side effects, and daily oral dosage of cyclosporine (Neoral) to maintain the target blood level of 850 to 1000 mg/dL at C2, 2 hours after the administration, were analyzed in the remaining 28 recipients. Results were compared to those obtained from a matched historical group (n = 28) of similar age, weight, and hepatic diseases distribution. None of the analyzed parameters was statistically significant (P >.05) except for the daily oral dose of cyclosporine (7 to 13 mg/kg/dose, P <.05). In our series, the addition of basiliximab to the immunosuppressive therapy did not reduce the incidence of AR in pediatric LT.

BACKGROUND.: Basiliximab, a monoclonal CD25 antibody has proofed effective in reducing acute rejection episodes in adults in various immunosuppressive regimens. The effect of basiliximab in the pediatric population is controversial. METHODS.: In a 12-month, double-blind, placebo-controlled trial, renal transplant patients aged 1 to 18 years were randomized to basiliximab or placebo with cyclosporine microemulsion, mycophenolate mofetil, and corticosteroids. The intent-to-treat population comprised 192 patients (100 basiliximab and 92 placebo). RESULTS.: The primary efficacy endpoint, time to first biopsy-proven acute rejection episode, or treatment failure by month 6, occurred in 16.7% of basiliximab-treated patients and 21.7% of placebo-treated patients (Kaplan-Meier estimates; hazard ratio 0.72, two-sided 90% confidence interval 0.416-1.26, n.s.). The rate and severity of subclinical rejections in protocol biopsies performed at 6 months posttransplant was higher in the basiliximab group (25.0%) than in the placebo group (11.7%). Patient and death-censored graft survival at 12 months was 97% and 99%, respectively, in the basiliximab cohort, and 100% and 99% among placebo-treated patients (n.s.). Renal function was similar in both treatment groups, and there were no significant between-treatment differences in the incidence of adverse events or infections. CONCLUSIONS.: Addition of basiliximab induction to a regimen of cyclosporine microemulsion, mycophenolate mofetil, and steroids resulted in a numerically lower but not significant incidence of biopsy-proven acute rejection versus placebo and excellent graft and patient survival at 1 year in pediatric renal transplant recipients. Whether this numerical difference is a true therapeutic benefit in view of the higher rate and severity of subclinical rejections in the basiliximab group in the protocol biopsy will be investigated in a long-term follow-up study. © 2008 by Lippincott Williams and Wilkins.

BACKGROUND.: Basiliximab (B), an anti-CD25 monoclonal antibody, may represent an alternative to steroids (S) in immunosuppression after liver transplantation (LTx). The aim of this prospective randomized clinical trial was to compare B with S in a cyclosporin A (CsA)-based immunosuppression regimen in primary LTx. METHODS.: Forty-seven adult recipients of LTx were randomly assigned to receive B or S. CsA was administered at the initial dose of 10 mg/kg/day and adjusted to the target C2 level of 800 to 1000 ng/mL by day 7. Clinically suspected acute cellular rejection (ACR) was histologically confirmed. Endpoints include ACR, survival, and disease-free survival. RESULTS.: In group B (26 patients), there were seven biopsy-confirmed ACR with an ACR rate of 15.4%; in group S (21 patients), 8 ACR with an ACR rate of 28.6% (P=n.s.). Cumulative survival at 36 months after transplantation was 84.3% for group B and 61.0% for group S. In hepatitis C virus patients (n=20: 12 in group B, 8 in group S), the ACR rate was 25% in group B and 50% in group S. The incidence of infection and other adverse events was similar in the two treatment groups. CONCLUSIONS.: B may represent a valid alternative to S in the induction of immunosuppression in LTx. Further studies of basiliximab in a large cohort are needed. © 2008 by Lippincott Williams and Wilkins.

BACKGROUND:

Reducing chronic steroid exposure is important to minimize steroid-related morbidity, particularly for susceptible renal transplant recipients. Steroid-free and steroid-sparing protocols have shown benefits, but safety has not been established for all populations. We investigated the safety of steroid avoidance (SA) in a population including African-Americans, using modern immunosuppression with protocol biopsy monitoring.

METHODS:

A randomized-controlled SA trial (early discontinuation, days 2-7) was conducted in a population (n = 77) including African-Americans and cadaveric kidney recipients. Patients received basiliximab, cyclosporine (CsA), and mycophenolate mofetil (MMF). In controls, steroids were tapered to 5 mg prednisone/d by day 30. Protocol biopsies were performed (1, 6, 12 and 24 months) to evaluate subclinical acute rejection (SCAR) and chronic allograft nephropathy (CAN).

RESULTS:

The SA did not result in significantly higher incidences of graft loss, AR, SCAR, CAN, or renal fibrosis. SA patients experienced similar renal function, comparable serum lipid levels, and a trend toward fewer cases of new-onset diabetes. Clinical outcomes of African-American and non-African-American patients did not significantly differ.

CONCLUSIONS:

The SA is safe in the context of basiliximab induction and CsA-based immunosuppression. This protocol could minimize steroid-related side effects in susceptible groups, including African-Americans, without increasing the risk of AR or graft failure.

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BACKGROUND:

Induction of immunosuppression with antibodies after heart transplantation decreases early acute rejection rate compared with placebo. We tested the non-inferiority of basiliximab vs rabbit anti-thymocyte globulin (RATG) on the incidence of acute rejection 6 months after transplantation.

METHODS:

From July 2002 to April 2004, 35 patients were enrolled in a multicenter, parallel group, open-label, non-inferiority trial. Patients were randomized to receive induction treatment with basiliximab (20 mg on Day 0 and 4) or RATG (125 mg on Day 0, 1, and 2). Standard maintenance therapy with cyclosporine, mycophenolate mofetil, and prednisone was used.

RESULTS:

Seventeen patients (aged 54 +/- 9 years old) received basiliximab, and 18 patients (aged 54 +/- 12 years old) received RATG. The freedom rate of rejection at 6 months (grade 3A or more) averaged 65% (11/17) with basiliximab and 83% (15/18) with RATG. The upper limit of the 1-sided 90% confidence interval for the difference RATG-basiliximab was 37.2%, exceeding the 22.5% non-inferiority margin. CD3 and CD4 levels were higher (p < 0.0001 for both), whereas CD25/CD4 and CD25/CD8 levels were lower (p < 0.0001 and p = 0.0462, respectively) in patients treated with basiliximab. One of the 14 basiliximab patients showed detectable cytomegalovirus viral load during the first 3 months after transplantation, whereas cytomegalovirus was detected by quantitative polymerase chain reaction in the plasma of 5 of the 13 RATG patients (p = 0.0505).

CONCLUSION:

Non-inferiority of basiliximab treatment for prophylaxis of acute rejection after heart transplantation could not be shown. RATG administration is associated with a higher rate of asymptomatic cytomegalovirus viral load detection in the plasma.