Low Risk Of Rejection Research Articles

Laparoscopic Procurement of Single Versus Multiple Artery Kidney Allografts: Is Long-Term Graft Survival Affected?

Living donor kidneys with multiple arteries (MA) are increasingly procured laparoscopically for transplant. We compare long-term graft function and survival of kidneys with single arteries (SA) and MA over a 10-year period. There were a total of 218 grafts with SA and 60 grafts with MA. The MA group had longer operative and ischemic times than SA group. There was a small increase in ureteral complication (8.3% vs. 2.3% P=0.06) and a significantly higher incidence of rejection (23.3% vs. 10.1%, P=0.01) in MA group than in SA group. Graft function was lower in MA group than SA group. The 5-year graft survival by Kaplan Meier analysis was better in SA group than in MA group (P=0.023). The estimated graft survivals at 1, 3, and 5 year were 94.4%, 90.6%, and 86% for SA group and 89.6%, 83.2%, and 71.8% for MA group. There was a higher percentage of graft loss from chronic allograft nephropathy in MA group than in SA group (16.7% vs. 5.5%, P=0.01). The presence of MA (vs. SA) was an independent risk for acute rejection (OR 3.60, 95% CI 1.59-8.14, P=0.002) and for graft loss (HR 2.31, 95% CI 1.05-5.09, P=0.038). Laparoscopic procurement of living donor kidneys with SA may be associated with a lower risk of rejection, better function, and superior long-term survival when compared with kidneys with MA.

Calcineurin inhibitor withdrawal and conversion to mycophenolate mofetil and steroids in cardiac transplant recipients with chronic renal failure: a word of caution

Chronic renal failure (CRF) is a common complication of calcineurin inhibitor (CNI)-based immunosuppression following cardiac transplantation (HTx). The aim of this prospective study was to evaluate the impact of an immunosuppressive conversion from CNIs to mycophenolate mofetil (MMF) and steroids in cardiac transplant recipients with CRF on renal and cardiac graft function. Since 1999, 12 HTx recipients (10 men; 58 +/- 3.6 yr of age; 8.7 +/- 4.2 yr after HTx) with CNI-based immunosuppression and a calculated creatinine clearance (CreaCl) <50 mL/min were included. Most patients (10/12) were on cyclosporine and two patients were on tacrolimus prior inclusion. MMF was started with 0.5 g/d and adjusted according to the target trough levels (2-4 ng/mL). Prednisone dosage was 0.4 mg/kg. Subsequently, CNIs were completely withdrawn. Acute rejection episodes were excluded one and three months after conversion by endomyocardial biopsy and by echocardiography every three months thereafter. After a mean follow-up of 20 +/- 16 months, CreaCl improved significantly: pre-conversion vs. post-conversion: 32.8 +/- 12.2 mg/dL vs. 42.8 +/- 21.14 mg/dL, p = 0.03. However, four acute rejection episodes occurred and patients were reconverted to CNIs. Additionally, six patients had a new onset of graft vessel disease (GVD) one yr after conversion. As a result of these adverse events, the study was stopped after inclusion of only 12 of the scheduled 30 patients. Conversion to MMF and steroids after HTx improves renal function, but increases the risk for recurrent rejection and GVD. Therefore, MMF and steroids should only be considered in patients with a markedly low risk for rejection.

Clinical Implications and Longitudinal Alteration of Peripheral Blood Transcriptional Signals Indicative of Future Cardiac Allograft Rejection

We have previously demonstrated that a peripheral blood transcriptional profile using 11 distinct genes predicts onset of cardiac allograft rejection weeks to months prior to the actual event. In this analysis, we ascertained the performance of this transcriptional algorithm in a Bayesian representative population: 28 cardiac transplant recipients who progressed to moderate to severe rejection; 53 who progressed to mild rejection; and 46 who remained rejection-free. Furthermore, we characterized longitudinal alterations in the transcriptional gene expression profile before, during and after recovery from rejection. In this patient cohort, we found that a gene expression score (range 0 to 40) of <or =20 represents very low risk of rejection in the subsequent 12 weeks: 0 progressed to treatable (ISHLT Grade > or =3A) rejection; 16 of 53 (30%) from the intermediate group (those who progressed to ISHLT Grade 1B or 2) and 13 of 46 (28%) controls (who remained Grade 0 or 1A) had scores < or =20. A gene score of > or =30 was associated with progression to moderate to severe rejection in 58% of cases. These two extreme scores (< or =20 or > or =30) represented 44% of the cardiac transplant population within 6 months post-transplant. In addition, longitudinal gene expression analysis demonstrated that baseline scores were significantly higher for those who went on to reject, remained high during an episode of rejection, and dropped post-treatment for rejection (p < 0.01). The use of gene expression profiling early after transplantation allows for separation into low-, intermediate- or high-risk categories for future rejection, permitting development of discrete surveillance strategies.

Islet-Like Clusters Derived from Mesenchymal Stem Cells in Wharton's Jelly of the Human Umbilical Cord for Transplantation to Control Type 1 Diabetes

BackgroundThere is a widespread interest in developing renewable sources of islet-replacement tissue for type I diabetes mellitus. Human mesenchymal cells isolated from the Wharton's jelly of the umbilical cord (HUMSCs), which can be easily obtained and processed compared with embryonic and bone marrow stem cells, possess stem cell properties. HUMSCs may be a valuable source for the generation of islets.Methodology and Principal FindingsHUMSCs were induced to transform into islet-like cell clusters in vitro through stepwise culturing in neuron-conditioned medium. To assess the functional stability of the islet-like cell clusters in vivo, these cell clusters were transplanted into the liver of streptozotocin-induced diabetic rats via laparotomy. Glucose tolerance was measured on week 12 after transplantation accompanied with immunohistochemistry and electron microscopy analysis. These islet-like cell clusters were shown to contain human C-peptide and release human insulin in response to physiological glucose levels. Real-time RT-PCR detected the expressions of insulin and other pancreatic β-cell-related genes (Pdx1, Hlxb9, Nkx2.2, Nkx6.1, and Glut-2) in these islet-like cell clusters. The hyperglycemia and glucose intolerance in streptozotocin-induced diabetic rats was significantly alleviated after xenotransplantation of islet-like cell clusters, without the use of immunosuppressants. In addition to the existence of islet-like cell clusters in the liver, some special fused liver cells were also found, which characterized by human insulin and nuclei-positive staining and possessing secretory granules.Conclusions and SignificanceIn this study, we successfully differentiate HUMSCs into mature islet-like cell clusters, and these islet-like cell clusters possess insulin-producing ability in vitro and in vivo. HUMSCs in Wharton's Jelly of the umbilical cord seem to be the preferential source of stem cells to convert into insulin-producing cells, because of the large potential donor pool, its rapid availability, no risk of discomfort for the donor, and low risk of rejection.

Noninvasive diagnosis of acute cardiac allograft rejection

Purpose of review Endomyocardial biopsy has been used for the last 25 years to screen patients for acute cellular cardiac allograft rejection. Limited by invasiveness, complexity, discomfort, complication proneness, interpretation variability, late detection of rejection and cost, the value of protocol endomyocardial biopsy as a screening method for patients at low risk of rejection has been questioned. Here, we review the latest evidence on noninvasive methods in the management of patients following cardiac transplantation. Recent findings Noninvasive modalities have been investigated recently as potential substitutes for endomyocardial biopsy. After completion of the human genome project, high-throughput transcriptomic methods rapidly spread to the field of transplantation. A molecular, gene expression-based classifier was developed and validated against endomyocardial biopsy as a screening test for rejection. Summary Endomyocardial biopsy is considered the standard method of surveillance for acute cardiac allograft rejection. The CARGO study was the first multicenter study to develop, validate and verify a gene expression profiling test to discriminate acute cellular cardiac allograft rejection from quiescence. The initial clinical experience reproduced the findings from CARGO and the first randomized clinical trial comparing conventional biopsy-based against gene expression profiling-based strategy is ongoing.

Late Steroid Withdrawal After Heart Transplantation and Incidence of Acute Rejection

Background Steroid withdrawal (SW) after heart transplantation (HT) reduces steroid-associated side effects, although it can increase acute rejection episodes (ARE). Patient selection criteria for SW and the time elapsed after HT for this maneuver are controversial issues. The objective of this study was to assess the safety of late SW after HT with regard to the occurrence of ARE and to analyze risk factors resulting in a poor evolution. Methods We studied a cohort of 24 patients who underwent SW late after HT. All of them had gone at least 4 years without any ARE. Independent variables were time after HT, general recipient and donor data, risk factors for ARE, and immunosuppression. The dependent variables were occurrence of ARE (proven or not proven with endomyocardial biopsy) and time and severity of ARE. Results Among 24 HT patients including 96% men with an overall mean age of 57 years who underwent SW, the mean follow-up was 2.32 ± 0.86 years. Six patients (25%) displayed an ARE ≥2R according to the International Society for Heart and Lung Transplantation (ISHLT) at 5 ± 3 months after SW. There were no deaths. Time from the last rejection episode to SW was 6.6 ± 2 years. All ARE were treated with steroid boluses (mean total dose 1583 ± 1044 mg). Among the HT patients with ARE, 5 (85%) had never experienced ARE after HT. Upon long-term follow-up, there were 2 deaths: 1 sudden death at 30 months after SW and 1 due to allograft vasculopathy at 20 months post-SW. Currently 92% are New York Heart Association (NYHA) functional class I with a mean left ventricular ejection fraction of 67% ± 10%. Conclusions In our series of HT with late SW after HT (even among an HT population with a low risk of rejection), there was a 25% rate of ARE. This study did not allow us to identify risk factors for ARE after SW. We believe that based upon these observations SW should be implemented with caution.

Cyclosporine Withdrawal Improves Renal Function in Heart Transplant Patients on Reduced-Dose Cyclosporine Therapy

Renal failure is a major cause of morbidity after heart transplantation. It is unclear whether calcineurin inhibitor (CNI) free immunosuppression provides more nephroprotection than low-dose CNI therapy. Thirty-nine patients with renal failure on low-dose cyclosporine A (CsA) were studied (62.9 +/- 8.7 years, five female, 8.2 +/- 4.3 years posttransplant, serum creatinine: 1.9 +/- 0.3 mg/dL, calculated GFR (cGFR): 48.2 +/- 18.3 mL/min, CsA C0 level: 64.0 +/- 19.9 ng/mL). All patients had been treated with low-dose CsA >6 months, renal function was stable or slowly decreasing (creatinine 1.7-3.5 mg/dL). Nineteen patients were randomized to discontinuation of CsA and overlapping rapamycin therapy initiation (RAPA), 20 patients continued low-dose CsA (control). Three patients (16%) discontinued rapamycin medication for side effects (diarrhea, skin rash), two patients developed pneumonia and pulmonary embolism, respectively, no rejection or other infectious complications were seen. After 6 months, renal function in the control group was unchanged. In the RAPA group, renal function markedly improved (creatinine: 2.08 +/- 0.15 to 1.67 +/- 0.13 mg/dL, cGFR: 48.5 +/- 21.4 to 61.7 +/- 21.4 mL/min (p < 0.001 within and between groups)). In carefully selected late survivors following heart transplantation who are at low risk of rejection, CNI-free rapamycin-based immunosuppression improves cGFR even in those already receiving low-dose CsA therapy. The results of this study warrant further confirmation in larger clinical trials that are powered to assess clinical outcomes.

Kinetics of Early Donor Chimerism after Nonmyeloablative Haematopoietic Stem Cell Transplantation Monitored with High-Resolution Real Time Quantitative PCR.

Purpose: From May 2003 to March 2005, 37 patients with haematological malignancies were transplanted with peripheral blood stem cells after nonmyeloablative conditioning with fludarabine 30 mg/m2 i.v. once daily on day −4 to −2 and 200 cGY of total body irradiation on day 0. Post-transplant immunosuppression consisted of oral cyclosporin 12.5 mg/kg/day and mycophenolate mofetil 30 mg/kg/day. Three patients were not eligible for follow-up due to lack of informed consent or informative markers for chimerism measurement. The purpose of this study was to evaluate kinetics of early chimerism of CD4+, CD8+, and, CD15+ cells immediately post transplant and furthermore to identify factors associated with rejection of graft.Methods: Blood samples were collected post transplant on day +1–3, +5–7, and then weekly. Samples were separated with immunomagnetic beads and DNA was salt extracted. Chimerism analysis was performed by automated high-resolution real-time quantitative PCR based on short insertion or deletion polymorphisms or single nucleotide polymorphisms.Results: The kinetics of CD15+ chimerism differed from that of CD4+ and CD8+ chimerism (Figure). CD15+ donor chimerism was low with a median of 0.9% donor cells on day +1–3, and remained low until around day +14. Subsequently the donor chimerism increased rapidly towards 100%. The CD4+ and CD8+ donor chimerism in contrast started higher with a median of 16.3% and 15.1% respectively on day +1–3, increased slowly, and took months to reach 100%. CD4+, CD8+ or CD15+ donor chimerism on day +1–3 did not predict later development of acute graft versus host disease. Two patients had primary rejection of the donor stem cells, while four patients had secondary rejection. The patients with primary rejection had no measurable donor chimerism in any cell lineages from day +1–3. No patient with CD15+ donor chimerism above the median (0.9%) on day +1–3 rejected, while 40% (6/15) of the patients with CD15+ donor chimerism below the median rejected (LogRank test, p=0.01). No differences were found in total number of nucleated cells, CD34+, CD3+, CD4+, or CD8+ cells in the donor harvest between patient who rejected and those who did not.Conclusions: The kinetics of early CD15+ donor chimerism differed from the kinetics of early CD4+ and CD8+ donor chimerism. Early CD15+ donor chimerism was markedly lower than CD4+ and CD8+ donor chimerism. CD15+ donor chimerism increased toward 100% donor chimerism more rapidly than the CD4+ and CD8+ chimerism. Primary rejection of donor stem cells can be identified early, as these patients have no measurable donor CD4+ or CD8+ chimerism on day +1–3. Furthermore, patients with CD15+ donor chimerism above the median on day +1–3 have a low risk for rejection. [Display omitted]

Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party

We have developed a reduced-intensity conditioning regimen for patients with severe aplastic anemia (SAA) undergoing alternative donor transplants, which includes fludarabine (120 mg/m(2)), cyclophosphamide (1,200 mg/m(2)) and antithymocyte globulin (7.5 mg/kg). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine and methotrexate. We have enrolled 38 SAA patients in this trial: median age of 14 (3-37) years, transplanted from unrelated (n=33) or family mismatched (n=5) donors, with unmanipulated marrow (n=36) or peripheral blood (n=2). Seven patients (18%) had evidence of graft failure, 11% developed grade II-III acute GvHD and 27% developed chronic GvHD. The actuarial 2-year survival is 73%, with a median follow-up of 621 days. Younger patients (<or=14 years) had a lower risk of rejection (5%) and improved actuarial survival (84%). Causes of death were infections (n=3), graft failure (n=2), Epstein-Barr virus lymphoma (n=2) and hemorrhage (n=2). In conclusion, the actuarial 2-year survival is encouraging in young SAA patients receiving a radiation-free conditioning regimen. The significant risk of graft failure in patients 15 years or older may require modification of the conditioning regimen in adults.

Use of Mycophenolate Mofetil in Liver Transplantation: A Literature Review

Mycophenolate mofetil (MMF) is an immunosuppressive drug, exhibiting its effect through inhibition of proliferation of T and B lymphocytes. Standard primary immunosuppressive therapy after orthotopic liver transplantation (OLT) is based on a calcineurin-inhibitor (CNI): cyclosporine or tacrolimus. Renal failure with arterial hypertension, due to CNI side-effects, is a major cause of morbidity and mortality after OLT. Several studies have shown the efficacy of MMF to improve CNI-induced nephrotoxicity, blood pressure, and uric acid concentration in liver transplant patients with concomitant reduction or withdrawal of CNI. Predose plasma mycophenolic acid concentrations (MPA) are related to adverse events, drug dose, and clinical status. Blood level values outside the suggested MPA therapeutic range are associated with acute rejection episodes and side effects, which have been described in about half of the patients treated with MMF. Most authors have described gastrointestinal and hematological side-effects, whereas these appear usually dose related, responding quickly to reduction. MMF is potent and safe immunosuppressive agent, and replacement of CNI by MMF in liver transplant patients with renal dysfunction may improve not only kidney function but also other CNI-associated side-effects, such as hypertension and hyperuricemia, with a low risk of rejection.

Blood Cyclosporine Level Soon After Kidney Transplantation is a Major Determinant of Rejection: Insights From the Mycophenolate Steroid-Sparing Trial

Target organs express antigens directly recognized by antigen-specific T cells, thereby precipitating rejection. When early T-cell activation is inhibited, there is a low risk of rejection. We sought to determine the predictive values of serial posttransplant blood cyclosporine trough (C 0) concentrations to minimize the risk for a first rejection episode compared with 2-hour postdose (C 2) drug concentrations. The final aim of the study was to identify a concentration range for the best predictive pharmacokinetic parameter that should be targeted to reduce the risk of rejection. This possibility was explored in 334 de novo kidney transplant recipients who participated in the prospective, multicenter Mycophenolate Steroid-Sparing Trial. Among measurements performed during the first 6 months postsurgery, cyclosporine C 0 levels measured early after transplantation were the strongest predictor of acute graft rejection. Levels within 300 to 440 ng/mL were associated with the lowest risk of rejection, while patients with levels lower than 300 ng/mL showed a more than double risk. Cyclosporine trough values predicted allograft rejection with an accuracy of 74%, while C 2 levels had no predictive value. These findings underline the need to target cyclosporine therapy early posttransplant to modulate T-cell activation.

Multivariate Analysis of Antibody Induction Therapy and Their Associated Outcomes in Deceased Donor Transplants

Aims The aims of this study were to describe factors associated with the use of overall induction, classes of induction agents, and to evaluate the incidence of acute rejection, short-term graft survival, and patient survival. Methods Of 24,901 transplants reported to the United Network for Organ Sharing (UNOS) between 1999 and 2001, 51% received induction therapy including Thymoglobulin (T; n = 3090), Simulect (S; n = 6063), or Zenapax (Z; n = 3755). Propensity scores (PS) were calculated to indicate factors associated with use of induction and for each induction agent. Outcome parameters included graft survival (GS), hazard ratio (HR) for graft loss (GL), and odds ratio (OR) for first-year acute rejection (AR). Results Pediatric (PS = 1.29; 95% confidence interval [CI] 1.12–1.49, vs adults) and retransplanted recipients (PS = 1.36; 1.23–1.49, vs first) were more likely to receive induction. One-year GS (90.1 vs 88.0%; P < .001), GL = 0.92% (0.86–0.98; P = .01), and AR free = 0.74 ( P < .001) were superior in patients receiving induction. Using multivariate analysis, the odds of rejection 0.73 (0.68–0.78), GL 0.91 (0.85–0.97), and death 0.90 (0.82–0.98) were lower in those receiving induction. Among patients given induction, those receiving T were more likely sensitized (PS = 1.50%; 1.31–1.71), retransplanted (PS = 1.51; 1.31–1.75), or had delayed graft function (PS = 1.75; 1.58–1.93). T decreased the odds of rejection compared with S or Z (OR = 0.74; 0.69–0.79), but the type of induction agent did not have an impact on graft outcome HR for T = 1.07 (0.96–1.19). Conclusions The use of antibody induction was associated with lower risk of rejection and better GS. There were no differences in GS among individual regimens. Comparative safety data were not analyzed but should be taken into consideration when choosing antibody preparations.

Serum TGF-β1 Correlates With Chronic Histopathological Lesions in Protocol Biopsies of Kidney Allograft Recipients

Introduction Transforming growth factor-β (TGF-β) is a well-known profibrotic factor playing a role in chronic kidney allograft nephropathy. Cyclosporine (CsA)-sparing immunosuppressive regimens may improve long-term graft function. Our aim was to study the influence of immunosuppressive treatment with versus without calcineurin inhibitors on serum TGF-β levels and histological changes in protocol biopsies of kidney allograft recipients. Patients and Methods In this prospective, randomized study of 42 low-rejection risk patients we randomized two groups: group A: mycophenolate mofetil (MMF), prednisone, daclizumab, and reduced CsA dose for 7 months (5 mg per kg per day) followed by complete withdrawal ( n = 21); and group B: normal CsA dose (10 mg per kg per day adjusted according to C 2 levels), MMF, prednisone, and no daclizumab ( n = 21). Methods In both groups we performed histological assessments (Banff 97) and measured serum TFG-β levels before as well as, at 3 and 12 months after transplantation. Results We found a relationship between immunosuppressive regimen and the TGF-β concentration over 1 year of observation. Before transplant the TGF-β1 levels did not differ between the groups ( P = .29); at 3 months they were 33 ± 9 vs 49 ± 15 pg per mL, respectively, in groups A and B ( P = .08), and at 12 months they were 39.5 ± 4 versus 55.5 ± 11 pg per mL, respectively, in groups A and B ( P = .03). Protocol biopsies at 12 months in group B showed chronic tubular lesions more pronounced than in group A. TGF-β1 concentrations were significantly higher among group B than A. We conclude that TGF-β1 concentration may predict the development of kidney graft fibrosis; early CsA withdrawal may achieve a reduction in chronic tubular and interstitial injury of cadaveric kidney allografts.

MULTIVARIATE ANALYSIS OF ANTIBODY INDUCTION THERAPY AND THEIR ASSOCIATED OUTCOMES IN DECEASED DONOR TRANSPLANTS

Abstract Aims The aims of this study were to describe factors associated with the use of overall induction, classes of induction agents, and to evaluate the incidence of acute rejection, short-term graft survival, and patient survival. Methods Of 24,901 transplants reported to the United Network for Organ Sharing (UNOS) between 1999 and 2001, 51% received induction therapy including Thymoglobulin (T; n = 3090), Simulect (S; n = 6063), or Zenapax (Z; n = 3755). Propensity scores (PS) were calculated to indicate factors associated with use of induction and for each induction agent. Outcome parameters included graft survival (GS), hazard ratio (HR) for graft loss (GL), and odds ratio (OR) for first-year acute rejection (AR). Results Pediatric (PS = 1.29; 95% confidence interval [CI] 1.12–1.49, vs adults) and retransplanted recipients (PS = 1.36; 1.23–1.49, vs first) were more likely to receive induction. One-year GS (90.1 vs 88.0%; P Conclusions The use of antibody induction was associated with lower risk of rejection and better GS. There were no differences in GS among individual regimens. Comparative safety data were not analyzed but should be taken into consideration when choosing antibody preparations.

Renal transplant recipients over aged 60 have diminished immune activity and a low risk of rejection

Strict consideration of the renal transplant candidate's chronologic age is generally supplanted by more subjective reflection on his (her) physiologic state. In the US, patients over 64 years old represented 9.0% of renal transplant recipients in the year 2000, yet little prior experience is available with which to guide the management of geriatric patients. Two hundred and forty six consecutive recipients of primary kidney transplants at the Yale-New Haven Organ Transplant Center between 1990 and 1995 were included in an outcome analysis. Age at transplantation ranged from 2 to 68 years; the study group consisted of the 16 (6.5%) over age 60. The immunosuppressive protocol was uniform for all patients. There was a disproportionately high use of cadaveric organs by older patients; only 1/16 (6.3%) received a living donor kidney. The overall rate of rejection within the first 90 days was 6.7% of cadaveric recipients over 60 versus 37.6% of younger recipients, P=0.001. Actual patient survival rates at 6 years were 100% of patients younger than 11 years versus 69% (11/16) of those older than 60 years. Death censored 5 year graft survival was 100% in older patients versus 85% among the younger patients. The older and younger patients received quantitatively equivalent immunosuppression, but acute rejection was uncommon in the former (6%) versus the younger cohort (34%). It seems logical to consider whether older renal transplant recipients may benefit from a less aggressive immunosuppression strategy.

Long-term results of heart transplantation in patients older than 60 years

Background Advanced age has been traditionally considered a relative contraindication for heart transplantation. Older patients are now considered as potential candidates for heart transplantation. The objective of this study was to evaluate the long-term results of heart transplantation in patients older than 60 years. Methods Between 1986 and 2001, 81 patients aged between 60 and 70 years (mean, 63 ± 2 years) underwent heart transplantation. These patients were compared with 403 adult recipients younger than 60 years (mean, 47 ± 11 years) who underwent transplantation during the same period. Results Thirty-day mortality was 6% (5/81) and 6% (25/403) in the older and younger patients, respectively ( P = NS). Actuarial survival at 1, 5, and 10 years was 88% ± 4% versus 83% ± 2%, 75% ± 5% versus 69% ± 2%, and 50% ± 9% versus 51% ± 3% in the older and younger patients, respectively ( P = NS). Older patients had significantly fewer rejection episodes ( P = .003). Freedom from allograft coronary artery disease at 1, 5, and 10 years was 98% ± 2% versus 92% ± 2%, 85% ± 6% versus 76% ± 3%, and 81% ± 7% versus 68% ± 3% ( P = .1). The incidences of infectious complication, cytomegalovirus infection, and posttransplant lymphoproliferative disorder were similar between the 2 groups, but older recipients were more likely to have a nonposttransplant lymphoproliferative disorder cancer ( P = .002). Age at transplantation was not identified as an independent risk factor for early and late death. Conclusion Heart transplantation in selected patients aged 60 years and older results in survival comparable with that of younger patients. Older patients have a lower risk of rejection but an increased risk of development of a nonposttransplant lymphoproliferative disorder cancer. Advanced age per se should not be considered as an exclusion criterion for transplantation.

Hepatitis C‐positive Donors in Heart Transplantation

Hepatitis C virus (HCV) can be transmitted to heart transplant recipients by donor organs. Mid-term results were reported using HCV-positive donors in patients at risk of imminent death (group I, n = 10), or in patients who otherwise would not have been offered heart transplantation (group II, n = 10) because of age (9/10) or associated medical risk (1/10). Medical records pertaining to patients receiving HCV-positive allografts between July 1994 and December 1999 were reviewed. The recipients consisted of 19 males and one female, with a median age of 54 years for group I and 66 for group II. The HCV RNA level, seroconversion of anti-HCV antibody, biochemical liver dysfunction, and causes of death were examined. Older recipients received reduced immunosuppression. Two patients in group II were HCV positive and were also retransplants. The hospital mortality rate was 10% in group I and 20% in group II; both hepatitis C-positive recipients died postoperatively prior to discharge. All predischarge deaths were related to multi-system organ failure (MSOF). All 17 survivors were HCV negative prior to transplant. Of these, 4/17 seroconverted. HCV RNA was detected in two of them. At a median follow-up of 26.4 months, 2/11 current survivors continue to test anti-HCV positive and are RNA negative. Three-year actual survival was 40% for group I and 70% in group II. Transplant coronary artery disease (TCAD) accounted for one postoperative death in group I. Current data show that four out of 11 survivors had developed TCAD at 3-year follow-up, yielding an actual freedom from TCAD rate of 12/17 (70%) at 3-year follow-up. Hepatitis C transmission using a donor heart as the reservoir is moderate (25%). Limited use of such donors is justified in selected patients. The risk for hepatic disease may be reduced by tailoring immunosuppression specifically for such recipients, particularly if they are at low risk of rejection. Further studies are necessary to define a possible association between HCV and TCAD.

Increased risk of CMV infection in heart transplant patients on mycophenolate mofetil

plantation (grp II, n58). Methods: Patients receiving HCV positive allografts between July 1994 to Dec. 1999 were reviewed. The HCV RNA level, seroconversion of anti-HCV antibody, hepatic enzymes, correlation of liver dysfunction and cause of death were examined. Survival and transplant coronary artery disease (TCAD) free rate were compared with age matched patients transplanted in the same period (n5 392). Results: The recipients consisted of 17 males and 1 female, with median age 54 yrs for grp I and 66 for grp II; 2 pts in grp II who were pretransplant HCV positive were also retransplants. Hospital mortality rate was 1/10 in grp I and 2/8 in grp II(total517 %), all from multiple organ failure. All survivors were HCV negative prior to transplant. At a median follow up of 26.5 months, 6/15 survivors (40 %) were infected with detectable viremia. Three(20 %) seroconverted after 1-13 months and two, one per grp, developed HCV related liver dysfunction. One from grp I developed fibrosing cholestatic hepatitis and expired. Actuarial 3 yr survival in those discharged is 56% and 84% for grp I and II. Freedom from rejection (.grade 3) was 40% for grp I and 100% for grp II. TCAD accounted for 2 late deaths in persistently seronegative but viremic pts in grp I and none in grp II. Overall 3-year TCAD free rate was 87% for the 15 patients discharged. Conclusions: (1) Under TDI, hepatitis C transmission using donor heart as the reservoir is moderate with seroconversion lower. (2) Limited use of such donors is justified in selected patients. (3) Seroconversion and risk for hepatic disease may be reduced by tailoring immunosuppression particularly if they are at low risk of rejection.

Alterations in T lymphocyte subpopulations associated with renal allograft rejection.

The peripheral blood OKT3 (total T), OKT4 (T helper/inducer), and OKT8 (T suppressor/cytotoxic) cells were determined by flow cytometry on twenty consecutive recipients of HLA-nonidentical cadaveric renal allografts. The absolute number of cells in all three populations decreased significantly posttransplantation, but no differences were found between patients experiencing rejection and those in quiescence. An OKT4/OKT8 ratio of greater than or equal to 1.7, either pretransplant or posttransplant, uniformly identified patients who subsequently experienced rejection. However, an OKT4/OKT8 ratio of less than 1.7 did not identify patients with a low risk of rejection. Pretransplant splenectomy was performed in 6 of 7 patients who rejected despite a low ratio. Serial monitoring of the OKT4/OKT8 ratio posttransplantation determined that an increase in the ratio of greater than or equal to 0.5 was a sensitive (81%) and specific (91%) indicator of a rejection episode. Graft survival was improved in patients with a high posttransplant OKT4/OKT8 ratio. These results indicate that the balance of helper and suppressor cell function may be of critical importance to the fate of an allograft, and that the alterations in this balance can be used to assist in the clinical management of allograft recipients.