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Objective: To describe a recent case of suspected interaction between oral cyclosporine modified and iron. Case Summary: A 33-year-old man underwent urgent cardiac transplantation for refractory cardiogenic shock caused by acute myocarditis. The patient had persistently low levels of cyclosporine despite a dose increase of the drug after the change of administration route from intravenous to oral. Spacing the administration of cyclosporine modified from oral iron resolved the problem. This drug interaction was reported as “probable” as determined by a Drug Interaction Probability Scale score of 7. Using this scoring system, the patient experienced a probable drug interaction between cyclosporine and iron both administered orally, and we surmise that the mechanism is that iron physicochemically destabilizes the cyclosporine microemulsion when both are administered concurrently. Discussion: This may be because of the interaction between cyclosporine microemulsion and iron because this cation can destabilize the immunosuppressant dosage form. Conclusions: Taking into account that joint administration of oral iron and cyclosporine modified can generate a physicochemical interaction that involves a decrease in the absorption of cyclosporine modified, we believe that it is necessary to recommend spacing administrations of both drugs as well as monitoring levels of cyclosporine in order to ensure optimal levels of immunosuppression.

Background: Cyclosporine (CsA) microemulsion pre-concentrate (MEPC) is a potential steroid-sparing agent for myasthenia gravis (MG) patients; however, there is a paucity of information on the long-term use of CsA MEPC in these patients. Objectives: We examined the efficacy and safety of CsA MEPC therapy administered to MG patients in a 2-year prospective open trial. Methods: From Hanamaki General Hospital and Keio University Hospital, 28 patients provided informed consent. They were enrolled in a prospective open study of CsA MEPC for the initial 6-month observation period; after this 9 were defined as poor responders and excluded from the long-term analysis. Results: The proportion of patients with minimal manifestations or pharmacologic remission status increased significantly. Among 18 patients taking oral prednisolone, 16 (88.9%) achieved a ≧50% reduction in prednisolone dose. Time to attain the minimal quantitative MG (QMG) score (4.2 ± 2.6) was 4.2 ± 4.2 months. Time to attain the minimal dose of prednisolone (2.9 ± 3.1 mg/day) was 9.3 ± 6.9 months. The dose of CsA MEPC was reduced to 2.6 mg/kg/day 2 years after starting the drug. Both total and ocular QMG scores were significantly decreased at 6 months and were generally maintained thereafter. The dose of prednisolone was significantly reduced at 1 year, and further reduced at 2 years. BMI decreased significantly, and 9 of 12 (75%) patients complaining of moon face reported that this had resolved on exit. All patients tolerated CsA MEPC without significant side effects. Conclusion: CsA MEPC therapy in responder MG patients suppressed disease severity, reduced steroid requirements, and alleviated steroid-related side effects. These findings should be confirmed by prospective controlled double-blind trials.

We retrospectively examined how the cyclosporine-A (CSA) microemulsion administration mode affected blood CSA levels, as well as how the dose and blood levels of CSA affected its therapeutic effect against systemic lupus erythematosus (SLE).We calculated the area under the blood concentration time curve (AUC) of CSA in 16 patients with corticosteroid-resistant SLE, and analyzed its correlation with CSA levels at the blood sampling time points to investigate the optimum monitoring and dosing regimen.The blood CSA level peaked at 2 h after administration (C2) in all patients. AUC0-6, which most markedly reflects the immunosuppressive effect, significantly correlated with C2 (R2 = 0.905), but not with the trough (C0). In concentration/dose ratio (C/D) of CSA, C2/D level was significantly higher when administered once daily before breakfast than when administered in the divided dose after meals (R2 = 0.355, P = 0.015), but not C0/D. During the 6-month follow-up, the CSA C2 tended to correlate with improvement in SLE disease activity index 2000 (R2 = 0.633, P = 0.067).The treatment with a single dose of CSA before breakfast, followed by monitoring of C2, may be useful for improving the therapeutic effect in patients with corticosteroid-resistant SLE.

In earlier registry analyses, cyclosporine at doses of3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST.Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (65 mL/min) included donor or recipient age60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point.Compared to higher doses, CsA-ME3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.

New immunosuppressive agents and regimens should be evaluated specifically in living donor liver transplant patients due to potential clinical and pharmacokinetic differences between deceased donor and living donor transplant recipients. The analysis presented here is the first direct comparison of clinical outcomes using cyclosporine microemulsion (CsA-ME) with monitoring of blood concentration at 2 hours postdose (C2) and tacrolimus-based immunosuppression in living donor liver transplantation. The analysis was conducted on the data provided by the 39 recipients of a living donor transplant out of the 495 patients enrolled in a 6-month, randomized, prospective, multicenter, open-label study (LIS2T). Patients were randomized to CsA-ME (C2 monitoring) or tacrolimus (monitoring of predose trough drug blood level [C0)]) and were administered corticosteroids with or without azathioprine. Twenty-three living-donor patients received CsA-ME and 16 received tacrolimus. By month 6, 9% of patients receiving CsA-ME and 19% of those receiving tacrolimus had lost their graft or died ( not significant [NS]). Nine episodes of biopsy-proven acute rejection were reported: 4 in the CsA-ME group (17%) and 5 in the tacrolimus cohort (31%, NS). There were no significant differences in any safety parameter between groups. The most frequently reported serious adverse events were infections, which occurred in 14 patients in the CsA-ME group (61%) and 13 patients in the tacrolimus arm (81%, NS). Twelve patients in the CsA-ME arm (52%) and 5 in the tacrolimus arm (31%, NS) discontinued the study prematurely. In conclusion, CsA-ME C2 monitoring or tacrolimus both offer effective protection against rejection in living donor liver transplants while maintaining a good safety profile. (Liver Transpl 2005;11:1395-1402.)

Increasing information suggests that absorption profiling may be superior to trough level monitoring for optimal concentration control of cyclosporine microemulsion (Neoral) therapy, and that CsA exposure early post-transplant may correlate significantly with reduced risk of acute graft rejection. This randomized, prospective, multicenter international concentration-controlled study was conducted in 21 renal transplant centers in 8 countries to test and compare the clinical feasibility, functionality, accuracy, precision and prediction of rejection by cyclosporine microemulsion absorption profiling to conventional trough-level drug monitoring. Primary or second renal allograft recipients treated with basiliximab, cyclosporine microemulsion and prednisone immunosuppression were randomized to two study groups in which cyclosporine microemulsion therapy was monitored using a multipointalgorithm or by trough levels. The two study arms were comparable in terms of baseline characteristics, treatment and clinical outcomes. Treatment failure, consisting of acute rejection, graft loss or death, occurred with equal incidence in the two groups (30% and 33%, respectively). Diagnostic feasibility, measured as the proportion of samples obtained within the designated time window, was marginally lower in area under the time-concentration curve (AUC) than in trough groups, but the therapeutic accuracy and precision were comparable or superior in the AUC group. Cox regression analysis performed across study groups showed a highly significant correlation between the predicted probability of acute rejection and cyclosporine (CsA) exposure measured by AUC over the entire 12-h dosage interval (AUC[0-12]) (p = 0.0068), AUC over the first 4 h of the 12-h dosage interval (AUC[0-4]) (p = 0.0014) or 2h post-dose (C2) CsA level (p = 0.0027). Day 3 dose- and weight-corrected C2 values (EMIT equivalent) separated patients into low (200 microg/L/mg/kg dose), intermediate (200-350 microg/L/mg/kg dose) and high absorber categories (350 microg/L/mg/kg dose), defining those at greatest risk. Within these categories, C2 values above approximately 1500 microg/L by day 3 post-transplant were associated with the lowest predicted probability of rejection. Comparable analysis by Cox regression using C0 levels did notreach statistical significance. Absorption profiling is a feasible, accurate and precise method for monitoring cyclosporine microemulsion therapy in clinical practice and, as shown in the companion article, may be simplified by the use of single-point C2 concentrations which accurately predict individual AUC[0-4] exposure levels. Both cyclosporine microemulsion relative absorption (i.e. dose- and weight-corrected exposure) and CsA exposure (measured by predicted AUC or C2 levels) are closely correlated with the risk of rejection, and define patients at high and low risk of acute graft rejection. Trough (C0) levels are not closely correlated with either CsA exposure or rejection risk, and should not be considered reliable for monitoring cyclosporine microemulsion therapy.

Recent data suggest that optimal cyclosporine (CsA) exposure early post-transplant significantly reduces the risk of acute graft rejection. They indicate that trough level monitoring is inadequate for precise concentration-controlled therapy, and suggest that absorption profiling may offer a superior approach for guiding clinical immunosuppression with Neoral. An international, prospective, multicenter study examined the feasibility, accuracy, precision and clinical utility of cyclosporine microemulsion (Neoral) absorption profiling in de novo renal transplant recipients receiving basiliximab immunoprophylaxis and cyclosporine microemulsion maintenance immunosuppression. The nested pharmacokinetic study reported here was conducted in 4 study centers in which full (11-point) pharmacokinetic profiles were performed on days 3, 7, 14 and 84 post-transplant to examine absorption profile and absorption efficiency, and to determine optimal sparse-sampling pharmacokinetic methods to predict Neoral exposure. Twenty-four patients had complete 12-h pharmacokinetic (PK) data on all 4 sampling days. Area under the time-concentration curve (AUC) over the first 4 h of the 12-h dosage interval (AUC[0-4]) and AUC over the entire 12-h dosage interval (AUC[0-12]) reached 3803 +/- 1033 and 7462 +/- 2120 microg.h/L respectively, by day 3, remained stable throughout the first 2 weeks, and declined to 2310 +/- 698 and 4062 +/- 1158 microg.h/L by day 84 (p0.001). AUC[0-4], capturing the drug absorption phase, represented 52% of the AUC[0-12] values across the four PK study days (mean R20.90). Between-patient variability was highest for C0 and C1 (mean coefficient of variation [c.v.] 36-47%), and lower for C2 (mean c.v. 28%) and subsequent time-points during the dosing interval. Mean relative CsA absorption, measured by dose- and weight-adjusted AUC[0-4] and AUC[0-12], increased significantly over time. The dose- and weight-corrected AUC[0-4h] (DWC.AUC[0-4]) rose by over 100% (p0.001) from 753 +/- 202 at day 3 to 905 +/- 232 at day 7, 1080 +/- 330 at day 14 and 1521 +/- 316 by day 84, while the dose-and weight-corrected AUC[0-12h] (DWC.AUC[0-12]) rose by over 80% (p0.001) from 1477 +/- 390 microg.h/L/ mg/kg on day 3, to 1721 +/- 426 on day 7, 2086 +/- 478 on day 14 and 2690 +/- 602 on day 84 (p0.001). Relative CsA absorption varied over 5-fold between patients at day 3, but patients tended to remain within the same quartiles over time. Sparse-sample modeling identified optimum 3-point, 2-point and 1-point predictors for AUC[0-4] and AUC[0-12]. C2 was the most accurate and robust .1-point predictor for AUC[0-4] (mean R2: 0.80), while C3 was superior for AUC[0-12] (mean R2: 0.75). C0 was not a good predictor of either AUC[0-4] or AUC[0-12] (mean R2: 0.13 and 0.24, respectively).Absorption profiling defines the heterogeneity in CsA exposure and relative absorption post-transplant. A 2-h post-dose blood sample is the most consistent, accurate and robust single-point predictor of the absorption phase measured by AUC[0-4] and should replace trough level monitoring for accurate concentration-control of Neoral therapy in the clinical setting. The use of additional samples at 1 and 3h is more complex and costly, but increases prediction accuracy and may be valuable in selected patients with erratic absorption.

Background. One-to-one (mg:mg) conversion from the conventional to the microemulsion formulation of cyclosporine (CsA) is advocated as a simple way to use the new therapeutic regimen. However, the potentially harmful effects of the conversion on kidney function in nonrenal transplant recipients are poorly known. Methods. Renal effects of the conversion were prospectively investigated in 22 pediatric liver transplant recipients (mean age, 8.4 years; mean time from transplantation, 3.2 years). Patients were followed for 12 months. Pharmacokinetic studies were performed at baseline and 5 days and 6 and 12 months after conversion. Results. Peak concentration, minimum concentration, average steady state concentration, and area under the concentration-versus-time curve increased by 60-130% after conversion. Graft losses, progressive deterioration of graft function, and acute rejection episodes did not occur. The mean glomerular filtration rate (GFR) was 103 ml/min/1.73 m 2 at baseline and 100 ml/min/1.73 m 2 after 12 months. However, 6 of the 22 patients showed at least a 15% (range, 16-38%) decrease in GFR between baseline and 6 months (P

c he 1990s ushered in approval of several novel immuosuppressant drugs, including mycophenolate mofetil, acrolimus, cyclosporine microemulsion, everolimus and irolimus, with consequent improvement in clinical utcomes. Subsequently, the transplant community has een challenged with the development and introducion of generic immunosuppression drugs. These drugs epresent a narrow therapeutic index and are thus lassified as critical-dose agents. Sengai Gibon, a Japaese zen monk, wrote “Whether for life, whether for eath—(it depends on) the right spoon-measure.” The urpose of this educational advisory is to provide an nternational perspective on regulatory and clinical oncerns with generic immunosuppression medicaions in thoracic transplantation.

Many medications have been discovered for the treatment of psoriasis, with methotrexate and cyclosporine being the earliest treatment options. They are complex structures that have shown efficacy, but both carry possible side effects and complications.

SUMMARY: Aim: Cyclosporine is known to improve proteinuria in nephrotic syndrome (NS), but is also associated with drug-related renal impairment. In this case series, therapeutic drug monitoring using the absorption profile was applied to adults with NS to investigate the efficacy and safety of once-daily administration of cyclosporine microemulsion (CSAME). Methods: Twenty patients received CSAME starting at 100–175 mg/day (1.4–3.1 mg/kg per day) once daily after breakfast. The area under the concentration–time curve up to 4 h after administration of cyclosporine (AUC0−4 h) was determined in each patient within 1 week after the start of CSAME treatment. Thereafter, the dose of CSAME was adjusted according to the absorption profile. Results: After 6 months, treatment with CSAME improved efficacy test values compared with those prior to treatment, and the severe nephrotic state was eliminated in all patients. No changes in serum creatinine or blood urea nitrogen levels were observed. The dose of CSAME was adjusted so that AUC0−4 h and the peak level fell within the range of target values, resulting in a significant decrease in the mean dose of cyclosporine (P = 0.0001). Time of peak level was variable among patients, but when CSAME was administered before breakfast, good absorption was achieved in all patients. Conclusion: By monitoring the absorption profile in patients with NS, a once-daily administration of CSAME was used to achieve both efficacy and a reduction in total exposure to the drug. Preprandial administration provided a more stable absorption profile of cyclosporine. The authors hope this method will become standard procedure during cyclosporine treatment in these patients.

Introduction The bioequivalence of generic formulations is established by measuring pharmacokinetic parameters in healthy volunteers. Cyclosporine (CsA) absorption and exposure is known to differ between healthy volunteers and transplant recipients. Therefore bioequivalence testing may be inadequate to ensure therapeutic equivalence. We sought to compare the efficacy of generic cyclosporine (ArpimuneME, RPG Life Sciences) versus Sandimmune Neoral in de novo renal transplant recipients. Methods A prospective single-center, open-label study enrolled 20 de novo renal transplant patients (group 1: mean age 30.55 ± 9.81 years, M:F 19:1, mean donor age 43.4 ± 10.8). All patients received ArpimuneME along with azathioprine and prednisolone. The results were compared with 17 matched controls (group 2: mean age 28.1 ± 9.5 years, M:F 13:4, mean donor age 47.8 ± 6.8) who received Neoral and were transplanted during the same period. C 2 levels were monitored by the cloned enzyme donor immunoassay (CEDIA). Results Patient and graft survivals were 100% and 100% and 100% and 92.8% in groups 1 and 2, respectively ( P = NS). Six patients (30%) experienced rejection in group 1 as compared eight patients (47.1%) in group 2. Mean CsA levels (ng/mL) during the first month were 1419.1 ± 213.6 and 1460.5 ± 290.7 and at 3 months, 1296.3 ± 227.8 and 1342.4 ± 303.4 in the two groups, respectively ( P = NS). The mean serum creatinine levels (mg%) in group 1 and group 2 were 1.6 ± 0.8 and 2.0 ± 1.4 at discharge and 1.5 ± 0.4 and 1.5 ± 0.8 at 6 months, respectively ( P = NS). Conclusion Use of a generic microemulsion form of CsA provided safe and effective immunosuppression compared with Sandimmune Neoral when drug monitoring was performed by C 2 levels.

BACKGROUND The clinical utility of C(2) monitoring of cyclosporine A microemulsion (CsA-ME) was evaluated in a prospective study of 110 patients more than 12 months posttransplant who demonstrated stable graft function and were receiving CsA-ME and steroids. METHODS Patients were converted to C(2) monitoring with the CsA-ME dose adjusted to a target C(2) range of 800 to 1,000 ng/mL and followed for 40 + 11 months. RESULTS At the time of conversion, 57% of patients exceeded the C(2) target, 20% of patients were below the C(2) target, and 23% of patients were within the C(2) target range. The mean dose of CsA-ME decreased from 258 + 88 to 202 + 76 mg/day (P < 0.0001), and the mean C(2) level decreased from 1,052 + 292 ng/mL to 896 + 233 ng/mL (P < 0.0002). There were no episodes of rejection. At last follow-up, 7.3% of patients had developed chronic renal allograft dysfunction. Use of antihypertensive agents decreased significantly (P = 0.0004), and mean total cholesterol decreased from 6.4 + 1.3 to 5.8 + 1.1 (P = 0.0009) after adoption of C(2) monitoring. CONCLUSION These findings suggest that conversion of maintenance renal transplant recipients from C(0) to C(2) monitoring of CsA-ME offers the clinical benefits of better control of hypertension and dyslipidemia, with effective protection against chronic renal allograft dysfunction. A target C(2) range of 800 to 1,000 ng/mL in maintenance patients receiving CsA-ME dual therapy seems appropriate.

To the Editor: During the past years C2 monitoring of cyclosporine microemulsion (CsA) has been focused on as a new, improved, and possibly more "correct" monitoring regimen in transplant recipients1,2,3. I read with great interest the publication by Perico et al4 in Kidney International. They concluded that among serial daily CsA measurements post-transplant, a CsA trough blood concentration of 300 to 440 ng/mL (and not C2) taken as early as day 2 has by far the highest capacity to predict rejection episodes. These results diverge from most recent publications. I register, however, that it is not stated in the text or in the tables or figures how many patients that were actually included in their final analysis. When reading the article, one gets the impression that 224 patients (334 patients minus 110 patients with delayed graft function) were included. From Table 3, which only includes data from 16 patients, one can calculate that the total material analyzed seems to be from only 39 patients [group below: 10 patients = 76.9% (i.e., 13 patients = 100%); group within:1 patient = 14.2% (i.e., 7 patients = 100%); group above: 5 patients = 26.3% (i.e., 19 patients = 100%)]. This is definitely not clear in the text and dramatically lowers the quality of the study. In Table 2, patients with no rejection have a C0 of 539 250 ng/mL compared to patients with rejection having a C0 of 335 248 ng/mL (N = 39?). How one can conclude from these data that a C0 on day 2 between 300 to 440 ng/mL is the best predictor needs to be explained.

The availability of a microemulsion formulation (ME) of cyclosporin (CyA) displays improved bioavailability and reduced inter and intra-patient variability, resulting in improved long-term outcomes. Recent developments in therapeutic drug monitoring stress the need to optimize peak drug levels during the early posttransplant period to obtain long-term benefit.We studied early CyA-ME pharmacokinetics, comparing pre- versus immediate posttransplant values, to assess predictability of pre-transplant profiles in 22 patients including 3 diabetics. An 8 mg/kg per day amount in two divided doses was administered, for 5 days pretransplant and 10-14 days posttransplant before performing the pharmacokinetic studies. Drugs interacting with CyA metabolism/absorption were withdrawn and patients with liver disease were excluded the CyA level monitoring used a 5-point blood sampling (at 0 hours, 1 hours, 2 hours, 3 hours, and 4 hours post-dose). The study compared actual concentrations at each individual time and the limited 0-4 hour AUC.The paired values at each point pre- and posttransplant were: C0 = 171 +/- 63 and 215 +/- 112, C1 = 723.86 +/- 345 and 1239.95 +/- 415, C2 = 972 +/- 185 and 1249.95 +/- 336, C3 = 822 +/- 242 and 942.7 +/- 286, and C4 = 601.54 +/- 190 and 670.5 +/- 208 ng/mL respectively. The C1 and C2 values were significantly higher posttransplant (P =.008 and 0.0045 respectively), suggesting a steeper absorption phase, a conclusion consistent with the higher 0-4 hour AUC posttransplant (P =.0089). However, linear regression analysis of pre- versus posttransplant values showed poor correlations.CyA absorption is significantly lower among patients on maintenance hemodialysis and showed no predictive correlation with posttransplant levels. The possible role of uremia in retarding absorption which may have clinical significance for primary graft dysfunction, needs further evaluation.

The past decade has witnessed unprecedented advances in renal transplantation propelled by novel and effective immunosuppression drugs. The introduction of mycophenolate mofetil (MMF), tacrolimus, cyclosporine microemulsion, sirolimus, a new generation of monoclonal antibodies (the anti–

Determine whether olestra alters the absorption of cyclosporine microemulsion in pediatric renal transplant recipients.Prospective, open-label, crossover pharmacokinetic study.General clinical research center in a university medical setting providing tertiary care.Seven pediatric-adolescent renal transplant recipients, ages 9 to 18, 5 to 24 months post-transplant with mean serum creatinine of 0.9 mg/dL (range, 0.7-1.6 mg/dL).Patients participated in 2 study periods: 1. Patients were given their usual dose of Neoral (Novartis Pharmaceuticals Corporation, East Hanover, NJ) without olestra, 2. patients were given their usual dose of Neoral combined with 0.35 g/kg (maximum of 16 g of olestra or approximately 2 ounces of Lays WOW [Frito Lay, Plano, TX] potato chips). The 2 study periods were separated by a minimum 7-day washout period. CsA blood concentrations were obtained at 1, 2, 3, 4, 6, 8, and 12 hours after drug administration.Each patient in the study had a consistent decrease in area under the curve (AUC) when given olestra along with their usual dose of Neoral, compared with giving Neoral alone (5,018 ng*hr/mL versus 4,086 ng*hr/mL; P.001). There also was a decrease in maximum concentration (Cmax) when Neoral was given with olestra compared with giving Neoral alone (1,202 ng/mL versus 876 ng/mL; P =.015). There was no statistical difference in the mean elimination rate or the trough values for both regimens (half-life 4.767 hours versus 4.771 hours and trough levels of 143 ng/mL versus 124 ng/mL).Olestra decreases total CsA exposure in pediatric renal transplant recipients. The noted decrease in AUC was not adequately predicted by CsA trough values which could lead to rejection episodes in the clinical setting.

have a positive donor-specific crossmatch, the following study was undertaken. Methods: Between 1985 and 9/2001, 450 patients underwent heart transplantation. We retrospectively reviewed the incidence and type of donor-specific crossmatch reactivity. Prior to 1991, NIH methodology was used and after 1991 AHG methodology was used. We further evaluated the treatments employed and the 1-year actual survival. Results: Of the 450 transplant recipients, 15 (3.3%) had a positive donor-specific crossmatch. Of these, 8/15 (53.3%) had a positive B-cell crossmatch, 11/15 (73.3%) had a positive-T cell crossmatch, and 3/15 (20.0%) had both a positive Tand Bcell crossmatch. Treatments included plasmapheresis (at least daily x 3) in 14 (93.3%), antilymphocyte antibodies in 14 (93.3%), and cyclophosphamide or mycophenolate mofetil in 14 (93.3%). One year survival tended to be worse 11/15 (73.3%) than the non-crossmatch positive patients 383/435 (88%) (p 0.10, OR 2.7, CI: 0.82-8.7). Of patients with a donor-specific crossmatch who died prior to one year, 2 had B-cell positive and 2 had T-cell positive crossmatches. None died of hyperacute rejection. All received plasmapheresis, antilymphocyte antibody, and cyclophosphamide or mycophenolate mofetil. Conclusion: Even with plasmapheresis, antilymphocyte antibody therapy, and cyclophosphamide or mycophenolate mofetil administration, one year survival maybe worse in heart transplant recipients with a positive donor-specific crossmatch. Unless other therapies can be shown to abrogate the worsened survival, cabsaion should be used in transplanting in the setting of a positive donor specific crossmatch.