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Phase II study of a moderate-intensity preparative regimen with allogeneic peripheral blood stem cell transplantation for hematologic diseases: the Texas Transplant Consortium experience.

Conventional preparative regimens for allogeneic stem cell transplantation are associated with excessive regimen-related toxicity (RRT) in some patients because of underlying comorbidities, advanced age, or prior treatment. We studied a preparative regimen designed to reduce RRT, yet allow for adequate engraftment and development of a graft-versus-malignancy effect. Thirty patients (median age, 57 years) were entered on study. Twenty-nine patientsreceived stem cells from HLA-identical siblings and 1 from a sibling mismatched for 1 antigen at the A locus. Sixteen patients had received previous stem cell transplants (6 allogeneic and 10 autologous). The preparative regimen consisted of fludarabine 30 mg/M2 per day IV on day -10 to day -5, busulfan 1 mg/kg per dose PO (n = 6) or 0.8 mg/kg per dose IV (n = 24) for 8 doses every 6 hours on day -6 to day -5, and horse-derived antithymocyte globulin 5 mg/kg per day IV (n = 12) or 15 mg/kg per day IV (n = 18) on day -4 to day -1. GVHD prophylaxis consisted of cyclosporine (CYA) 3 mg/kg BID PO starting on day -3 (n = 13) or CYA and methotrexate 15 mg/m2 IV on day +1 and 10 mg/m2 IV on day +3 and day +6 (n = 17). The median number of CD34 cells transplanted was 3.19 x 10(6)/kg. All patients demonstrated recovery of hematopoietic function. Twenty-six (89%) of 29 evaluable patients achieved greater than 90% donor cell chimerism before day 100. Three patients never achieved greater than 90% donor chimerism, and another 3 patients subsequently lost donor chimerism. All 6 of these patients had autologous reconstitution with progressive disease. RRT was minimal; 7 patients had greater than grade II nonhematologic toxicity and there were no toxic deaths attributable to the conditioning regimen. Transplantation-related mortality was 7% (95% confidence interval [CI], 6%-8%) at 3 months and 28% (95% CI, 23%-34%) at 12 months after transplantation. Non-relapse-related mortality was most often due to infection. Grade II or greater GVHD developed in 56% of evaluable patients, and all patients with disease response developed GVHD. Actuarial estimates of overall and disease-free survival at 12 months were 52% (95% CI, 43%-63%) and 30% (95% CI, 24%-37%), respectively. Although this preparative regimen allowed adequate engraftment with minimal RRT, GVHD and infectious complications caused significant morbidity and mortality. Further study to define appropriate patient populations for this regimen, while limiting GVHD and infection risks, is needed.

Adult↗

The potential role of bone marrow transplantation in augmenting donor-derived immunity to hepatitis B after rat liver transplantation.

Adoptive transfer of immunity to hepatitis B virus (HBV) is not provoked solely by bone marrow, but also by liver transplantation, although transiently. In the current study, simultaneous bone marrow transplantation, which possibly can increase the number of antibody-secreting cells, was performed to augment the efficacy of transferring HBV immunity. Stimulation of donor-derived immune cells by postoperative vaccination was used to investigate whether a secondary immune response can be induced in recipients. Orthotopic liver transplantation (n = 28), performed in three rat strain combinations representing different genetic constellations, was compared with bone marrow-augmented liver transplantation (n = 21). Donors had been vaccinated twice with recombinant hepatitis B surface antigen (HBsAg). Recipients surviving more than 10 weeks received a boost vaccination. All animals were monitored weekly for the presence of antibodies to HBsAg (anti-HBs). Effective anti-HBs titers were measured in 82% of liver recipients (23 of 28 recipients) and lasted from 2 to 9 weeks. Ninety percent of bone marrow-augmented liver recipients (19 of 21 recipients) seroconverted, with anti-HBs persisting from 2 to 12 weeks. A greater seroconversion rate, prolonged titer duration, and different pattern of titer development were observed in bone marrow-augmented liver recipients, although statistical significance could not be obtained because of the small numbers of comparable animals. Posttransplantation vaccination in recipients of combined grafts did not arouse a typical secondary antibody response, but showed a tendency toward an earlier and stronger response to vaccine in comparison to recipients without immune transfer. Simultaneous bone marrow transplantation showed an augmenting, but limited, effect on humoral immune transfer. Therefore, other potentially promising cellular strategies, such as transfer of in vivo and ex vivo stimulated antigen-specific cells should be pursued further. Improvement of the effect of postoperative vaccination possibly can be achieved by optimizing the immunization protocol.

Animals↗

Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen.

We studied the clinical outcomes of 171 adults with hematologic malignancies who received unrelated cord blood transplantation (CBT) as a primary unrelated stem-cell source (n=100), or bone marrow transplant (BMT) or peripheral blood stem-cell transplant (PBSCT) from related donors (n=71, 55 BMT and 16 PBSCT). All patients received myeloablative regimens including 12 Gy total body irradiation. We analyzed the hematologic recovery, and risks of graft-versus-host disease (GVHD), transplantation-related mortality (TRM) and relapse, and disease-free survival (DFS) using Cox proportional hazards models. Significant delays in engraftment occurred after cord blood transplantation; however, overall engraftment rates were almost the same for both grafts. The cumulative incidences of grades III to IV acute and extensive-type chronic GVHDs among CBT recipients were significantly lower than those among BMT/PBSCT recipients. Multivariate analysis demonstrated no apparent differences in TRM (9% in CBT and 13% in BMT/PBSCT recipients), relapse (17% in CBT and 26% in BMT/PBSCT recipients), and DFS (70% in CBT and 60% in BMT/PBSCT recipients) between both groups. These data suggest that unrelated cord blood could be as safe and effective a stem-cell source as related bone marrow or mobilized peripheral blood for adult patients when it is used as a primary unrelated stem-cell source.

Adolescent↗

Integrating palliative care for liver transplant candidates: "too well for transplant, too sick for life".

Chronic liver disease results in more than 1 million physician visits and more than 300,000 hospitalizations per year in the United States. More than 27,000 patients annually progress to end-stage liver disease (ESLD), liver failure, or death. Patients with ESLD experience such complications as encephalopathy, malnutrition, muscle wasting, ascites, esophagogastric variceal hemorrhage, spontaneous bacterial peritonitis, fatigue, and depression. Despite significant improvements in palliation, patients' quality of life diminishes and their disease will often inexorably progress. Liver transplantation, a valid treatment option, increases life and reduces many symptoms. With the current shortage of organs, up to 10% to 15% of these patients die without receiving an organ. Many patients also are not candidates for transplantation due to comorbid illness. In addition, some patients receive a transplant but succumb to complications of the transplant itself. Such patients and families face the conundrum of a potentially treatable yet often fatal illness. Through the case of a 55-year-old woman with a life-long history of hepatitis B virus infection who is awaiting transplant, we discuss the transplant eligibility process and the struggle with maintaining hope for a cure in the face a life-threatening illness. In all of these circumstances, the health care team must combine elements of palliative care with life-sustaining therapy to maximize the patient's quality and quantity of life.

Female↗

Hepatopulmonary syndrome after living donor liver transplantation and deceased donor liver transplantation: a single-center experience.

Hepatopulmonary syndrome (HPS) is a progressive, debilitating complication of end-stage liver disease. In contrast to the well-established reversal of HPS after deceased donor liver transplantation (DDLT), little has been written about the natural course of HPS after the newer procedure of living donor liver transplantation (LDLT). We describe HPS in a small series of 4 liver transplant recipients (2 DDLT; 2 LDLT) at a single center. Before transplantation, these 4 patients had a mean shunt fraction of 23.6 +/- 14.3% and a mean PaO2 of 58.5 +/- 11.3 mm Hg. All 4 patients used supplemental oxygen before transplantation. Sixteen weeks after transplantation, all 4 patients had normalized or improved shunt fraction and PaO2. These patients regained normal pulmonary function within a few months, despite the period of hepatic regeneration after LDLT. In conclusion, both DDLT and LDLT are associated with rapid and dramatic reversal of HPS.

Adult↗

Two-stage total hepatectomy and liver transplantation for acute deterioration of chronic liver disease: a new bridge to transplantation.

Two-stage total hepatectomy and liver transplantation has been reported for acute liver disease such as fulminant hepatic failure, primary graft failure, severe hepatic trauma, and spontaneous hepatic rupture secondary to hemolysis, elevated liver function tests, low platelets syndrome, and preeclampsia. This is the first report of patients with cirrhosis to undergo a 2-stage total hepatectomy and liver transplantation. From 1984 to 2002, our institution performed 2008 orthotopic liver transplantations. We identified 4 patients with chronic liver disease who underwent a 2-stage hepatectomy and liver transplantation. This is a retrospective review of these 4 patients and a review of the literature on this procedure. All 4 patients were young men with an age range of 29-31 years and had underlying cirrhosis as well as a previous transjugular intrahepatic portosystemic shunt (TIPS)procedure. Acute decompensation fulfilling Ringes' criteria for toxic liver syndrome secondary to an upper gastrointestinal bleed occurred in all patients. The approximate average time between hepatectomy and liver transplantation was 20 hours (range: 8-42 hours). In all cases, the explanted liver showed histological changes of acute hepatic necrosis within the background of cirrhosis. After hepatectomy, vasopressor requirements were well documented in 2 patients. For 1 patient, there was a clear improvement in their hemodynamic status. The mean hospital stay of the 4 patients was 63 days. All patients were discharged from the hospital and are alive and well with adequate liver function at 6 to 37 months follow-up. Two-stage total hepatectomy and liver transplantation may be a life-saving procedure in highly selected cirrhotic patients with acute hepatic decompensation and multiorgan dysfunction.

Adult↗

Outcomes in liver transplant recipients with hepatitis B virus: resistance and recurrence patterns from a large transplant center over the last decade.

Hepatitis B virus (HBV) recurrence following liver transplantation (LTx) has been controllable primarily with the use of hepatitis B immune globulin (HBIg) and lamivudine (LAM). However, HBV resistance to LAM and/or HBIg has become an increasing problem prompting the use of newer antiviral agents. The purpose of our study was to investigate the association between therapy, HBV breakthrough, and allograft / patient survival in HBV-positive liver transplant recipients. We performed a retrospective review of the medical records of patients that were transplanted for HBV from June 1994 to May 2003. A total of 92 patients, positive for either hepatitis B surface antigen (HBsAg) or HBV deoxyribonucleic acid (DNA) pretransplant, received LAM monotherapy or HBIg (6 months) plus LAM therapy post-liver transplant. HBV breakthrough post-LTx was noted in 14 patients. All patients had detectable HBV DNA prior to liver transplantation; none of the patients that were HBV DNA negative prior to transplant had detectable HBV DNA posttransplant. Of these 14, 9 patients (64%) were switched from LAM to adefovir dipivoxil (ADF) and 5 patients (36%) to tenofovir disoproxil fumarate (TNV). In conclusion, pre-LTx HBV viremia should be considered in planning post-LTx prophylaxis. Trials to evaluate oral antiviral agents in combination with or without HBIg therapy are needed.

Adenine↗

Tracheal transplantation. III. Demonstration of transplantation antigens on the tracheal mucosa of inbred rat strains.

Tracheal transplants were performed on inbred strains of rats. Monoclonal antibodies were used in combination with the biotin-avidin technique for demonstrating donor-specific RT1 Ac transplantation antigen. Transplantation antigens were predominantly contained in the tracheal mucosal cells. No donor-specific antigens could be found in the mucosa of transplants which survived orthotopic tracheal transplantation for longer than 210 days. This suggests that the mucosa of the transplant is rejected and replaced by a mucosa from the recipient.

Animals↗

Analysis of hypertension in children post renal transplantation--a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Hypertension is common in children after renal transplantation and is associated with multiple factors. Data regarding the prevalence of post-transplant hypertension and the relationship between immunosuppressive drugs and the persistence of hypertension in a large population of North American children have not been available. This study was designed by the North American Pediatric Renal Transplant Cooperative Study to evaluate in a large diverse multicenter population of children the prevalence of hypertension post transplantation, the type of antihypertensive medications used to treat this hypertension and to determine the relationship between the blood pressure control and the immunosuppressive therapy. Analysis of 277 patients showed the following: (1) 70% of recipients required antihypertensive medications 1 month post transplant compared with 48% pre transplant; the incidence decreased to 59% at 24 months; (2) the majority of children received multiple drug therapy to control blood pressure; (3) hypertension can be controlled effectively despite inherent etiological factors, such as allograft source, prior hypertension and immunosuppressive therapy.

Adolescent↗

Maintenance immunosuppression therapy and outcome of renal transplantation in North American children--a report of the North American Pediatric Renal Transplant Cooperative Study.

The North American Pediatric Renal Transplant Cooperative Study collects extensive data on all transplants entered into its registry. For this study we evaluated 568 cadaver kidney and 492 live-donor recipients with graft function at 30 days post transplant. Utilizing maintenance immunosuppressive therapy at 30 days post transplant, we evaluated patient and graft outcome, mortality and morbidity over the first 6 months post transplant. For cadaver kidney recipients, 36 patients were receiving prednisone and azathioprine (PA), 114 were maintained on prednisone and cyclosporine (PC) and 418 were on prednisone, cyclosporine and azathioprine (PCA). Patients receiving PA had a greater incidence of rejection prior to 30 days, a greater incidence of hospitalization for rejection and for hypertension over the next 6 months and a greater loss of allograft in the first 6 months compared with the other two groups. The only difference noted between PC and PCA was a lower serum creatinine in the PCA group at 6 months. For living-related kidney recipients, there were 78 patients maintained on PA, 97 on PC and 317 on PCA. Again patients receiving PA had a higher rate of hospitalization for rejection and a higher rate of graft loss. When patients receiving PC were compared with those receiving PCA, no differences were noted in the 6-month serum creatinine values, but a greater percentage of PCA patients were receiving antibiotics on day 30. We conclude that PA is poor therapy for both groups, PCA is ideal therapy for cadaver kidney recipients, but no beneficial effects are noted when PCA is used over PC for live-related donor kidney transplants.

Adolescent↗

Two good reasons for an angiotensin-II type 1 receptor blockade with losartan after cardiac transplantation: reduction of incidence and severity of transplant vasculopathy.

Despite considerable progress in immunosuppressive therapy, the incidence and severity of transplant vasculopathy (TVP) after cardiac transplantation have not declined. The renin-angiotensin system (RAS) plays a pivotal role in the proliferation of vascular smooth muscle cells (VSMCs) contributing to TVP. We compared the effects of an angiotensin-II blocker, losartan (AT(1) blocker), and an angiotensin-converting enzyme (ACE) inhibitor, enalapril, on the incidence of diseased vessels and the severity of experimental TVP in the Lewis-to-Fischer rat heterotopic heart transplantation model. Recipients were randomly divided into six groups, group 1: no therapy, group 2: 3 mg/kg per day cyclosporine (CyA) s.c., group 3: CyA and 10 mg/kg per day losartan p.o., group 4: CyA and 40 mg/kg per day enalapril p.o., and groups 5 and 6: as groups 3 and 4, but additionally pre-treated with losartan or enalapril 7 days prior to transplantation. Eighty days after grafting, we assessed the incidence and severity of TVP, expressed as percentage of diseased vessels and mean vessel occlusion (MVO), by digitizing morphometry. CyA and CyA/enalapril post-treatment significantly reduced MVO, compared with controls, but not the incidence. Additional reduction of MVO was achieved in CyA/enalapril pre-treatment and both CyA/losartan pre- and post-treatment groups when compared with CyA and untreated controls. However, only losartan post-treatment in combination with CyA reduced both incidence and MVO. Our results validate the important role of the RAS in neointimal proliferation after cardiac transplantation. Losartan appears to be superior to enalapril in preventing TVP after experimental cardiac transplantation. Therefore, AT(1) blockade with losartan might be a therapeutic option for the prevention of TVP in human heart recipients.

Acute Disease↗

Limited sampling strategies using Bayesian estimation or multilinear regression for cyclosporin AUC(0-12) monitoring in cardiac transplant recipients over the first year post-transplantation.

OBJECTIVE: The aim of this study was to develop routinely applicable limited sampling strategies for assessing cyclosporin (CsA) AUC(0-12 h), and possibly other exposure indices such as AUC(0-4 h) and C(max), in heart transplant patients over the first year post-transplantation. METHODS: First, the individual pharmacokinetics (PKs) of 14 adult heart-transplant patients receiving Neoral were assessed at three post-transplantation periods, at the end of the first week (W1), the third month (M3) and the first year (Y1). To fit blood concentrations, a PK model specially developed for oral CsA was applied. Second, two statistical methods were compared for AUC(0-12 h) estimation using a limited sampling strategy (maximum of three blood samples): multiple regression analysis (MR) and Bayesian estimation (BE). RESULTS: No significant difference was observed between the individual PK parameters at M3 and Y1, so population modelling was performed taking as a whole the concentration data collected at M3 and Y1. On the contrary, a significant difference ( P<0.05) was found for the C2/dose ratio between W1 and M3 and between W1 and Y1 (mean+/-SD =5.47+/-2.33; 7.78+/-1.05; 6.98+/-2.17 ml(-1 )for W1, M3 and Y1, respectively). Also, C(max)/dose and A were found significantly lower at W1 than at M3 ( P<0.01 and P<0.005, respectively), while lambda(1) was significantly higher at W1 than at both M3 and Y1 ( P<0.01). Using three sampling times (t0 h, t1 h and t3 h), BE allowed an accurate prediction of AUC(0-12 h) (mean bias =3.06+/-12.16%; +1.50+/-1.61%; and -0.20+/-11.42% at W1, M3 and Y1, respectively), AUC(0-4 h )and C(max). MR led to satisfactory estimation of AUC(0-12 h) using only two blood samples collected 2 h and 6 h post-dose (R=0.956-0.993; bias =-5.22 to +4.41; precision =6.38 to 9.90%), but this method is unable to estimate any other exposure index and requires strict respect of sampling times, contrary to BE. CONCLUSION: Neoral monitoring based on full or abbreviated AUC is possible using BE or MR in heart transplant patients over the first year post-transplantation. BE provides a good description of the individual PK profiles and thus might be useful not only in case of potential discrepancies between C2 and clinical findings, but also for clinical trials aimed at finding optimum PK monitoring in heart recipients.

Area Under Curve↗

Two-hour post-dose cyclosporin A levels in adolescent renal transplant recipients in the late post-transplant period.

Although the success of renal transplantation is closely linked to the immunosuppression provided by cyclosporin A (CsA), the best way to monitor the blood levels of CsA is still not clear. Trough CsA levels (C(0)) are commonly used, but the 2-h post-dose CsA levels (C(2)) are reported to correlate better with area under the curve. The aim of this study was to evaluate the correlation of C(2) levels with allograft function in adolescent renal transplant recipients in the late post-transplant period (6 months after transplantation) compared with C(0 )levels. The data of 17 adolescent renal transplant recipients (12 males, 5 females) were evaluated retrospectively. The mean age at the time of transplantation was 15.212+/-2.918 years and the mean follow-up period was 53.172+/-34.090 months. C(0) levels correlated with oral CsA and diltiazem doses, while C(2) levels exhibited no correlation. When C(2) levels were classified as 0-400, 401-800, and 801-1200 ng/ml, no statistically significant difference was found between these groups with respect to glomerular filtration rate (P=0.830). Although 82% of the patients had C(2 )beneath the therapeutic level (<800 ng/ml), none had an acute rejection episode. In conclusion, optimum C(2) levels could be different from levels in the adult population. Furthermore, the correlation of C(2) levels with CsA dose seems to be weaker than in the adult population. Thus, further studies are needed to determine a more reliable predictor for CsA dose monitoring and target blood CsA levels in adolescent patients.

Adolescent↗

Center volume effects in pediatric renal transplantation. A report of the North American Pediatric Renal Transplant Cooperative Study.

An inverse relationship between mortality and center volume has been established for several surgical procedures. Given the distinctiveness of pediatric renal transplantation and the large variation in center volume, investigation for relationships between center volume and graft outcome was pursued using the North American Pediatric Transplant Cooperative Study database. Center volume groups were based on the total number of pediatric transplants reported from 1987 to 1995. Centers reporting > 100, 51-100, or < or = 50 transplants were grouped as high- (n=11), moderate- (n=28), or low-volume (n=65), respectively. Differences between groups included increasing rates of cadaver donor graft thrombosis (2.4%, 4.3%, and 5.7%, P<0.01) and acute tubular necrosis (ATN) (10.2%, 11.5%, and 14.0%, P<0.01) with decreasing center volume. Treatment differences included a higher rate of induction with an anti-T-cell antibody preparation in the larger-volume groups, 60.2%, 51.8%, and 39.2% (P<0.001). Decreasing graft survival for decreasing center size groups was noted at 3 months post transplant, 90.4%, 90.2%, and 88.4%. These differences were significant only with the exclusion of anti-T-cell induction from the proportional hazards model (relative risk=0.81 and =0.70 for the moderate- and high-volume groups, P<0.02). Superior graft survival in the high-volume centers noted at 3 months post transplant appears predominantly the result of lower rates of cadaver donor graft thrombosis and ATN. Analysis points to the need for low-volume centers to identify risk factors influencing these outcomes.

Cadaver↗

Cardiac transplantation for the cardiologist not trained in transplantation.

This review focuses on selected aspects of the treatment of patients being evaluated for and undergoing cardiac transplantation. Cardiac transplantation is a potential therapeutic option for a variety of irreversible cardiac disorders when the symptomatic status and anticipated survival after transplantation exceeds that of the patient's condition. The timing of cardiac transplantation with respect to prognosis is aided by the measurement of baseline hemodynamics and maximal aerobic capacity. Major cardiac problems that occur after transplantation include an increased early risk of acute allograft rejection and, later, the occurrence of allograft coronary artery disease. Furthermore, cardiac transplant recipients have unique "normal" physiologic alterations with respect to intracardiac hemodynamics, exercise capacity, the effects of denervation, and expected electrocardiographic and echocardiographic findings.

Heart Failure↗

Double-lung transplantation for cystic fibrosis. The Cystic Fibrosis Transplant Study Group.

One hundred twenty cystic fibrosis patients were accepted for transplantation. Twenty-five patients underwent double-lung transplantation. Twenty-five patients died awaiting transplantation (20.6%). There were 13 female and 12 male patients. Their mean age was 28 years (range, 7 to 34 years), and mean percentage ideal body weight was 76% (range, 58.5% to 91.9%). Most patients were hypoxic and hypercarbic. Two patients underwent tracheal anastomosis, 15 had en bloc bronchial anastomoses, and 8 had sequential single-lung transplants. Operative mortality was 16%; all deaths were related to bleeding from extensive adhesions. Actuarial survival at 1 year was 64%. Rejection and infection were frequent during the first month and decreased thereafter. Airway complications occurred in 5 patients but were amenable to laser therapy and stenting. We conclude that double-lung transplantation is an acceptable modality for the treatment of cystic fibrosis patients with end-stage lung disease. It may be a better alternative to heart-lung transplantation considering the paucity of thoracic organ donors.

Adolescent↗

Demography and survival of patients receiving treatment for chronic renal failure in Australia and New Zealand: report on dialysis and renal transplantation treatment from the Australia and New Zealand Dialysis and Transplant Registry.

There were 7,059 (403 per million) Australian patients and 1,341 (388 per million) New Zealand patients receiving renal replacement treatment at the end of 1992. Fifty-three percent and 50%, respectively, were dependent on a functioning transplant, 87% and 80%, respectively, from a cadaver donor. In Australia the majority of dialysis patients depended on hemodialysis (68%) and continuous ambulatory peritoneal dialysis (CAPD) (31%); 68% of patients were dialysing at home or in a satellite (free-standing) facility. The majority (62%) of home dialysis patients used CAPD treatment. In New Zealand there were 44% of patients on hemodialysis; 83% dialyzed at home and the majority (65%) used CAPD treatment. Few dialysis units (five of 71) in Australia were "for-profit" facilities; there was none in New Zealand. Universal health care has been available for renal replacement treatment for 20 years. The annual incidence of new patients increased steadily during the past 10 years, to 61 per million (Australia) and 69 per million (New Zealand) in 1992. There were disproportionate numbers of indigenous Australian Aboriginals (51%), New Zealand Maoris (30%), and Polynesian Pacific Islanders (11%) compared with their distribution in the general population. There was a considerable increase in elderly and diabetic patients during the period from 1983 to 1992: in Australia, 25% of patients were over 65 years of age and 14% of patients were diabetic, and in New Zealand, 16% of patients were over 65 years of age and 25% of patients were diabetic. The renal transplantation rate has remained unchanged since 1983 at 27 per million in Australia, but has increased markedly from 20 to 33 per million in New Zealand. The annual transplantation rate was 20% to 30% of those patients aged 15 to 64 years who were likely to be transplanted. The multifactorial analysis of risk factors for survival of dialysis patients showed age, male gender, CAPD treatment, Aboriginal race, and diabetic or analgesic nephropathy to be associated with lower rates of survival. Deaths were commonly due to a cardiac cause (43%), mostly myocardial infarction, or to infection (17%) or withdrawal from treatment (14%). The overall death rate was 12% of patients at risk in 1992. Multifactorial analysis of risk factors for graft survival in transplanted patients showed patient age, diabetic nephropathy, donor age, single-drug regimen, and low transplant activity (operations) at a center to be associated with lower rates of survival.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Symptom complex is associated with transplant coronary artery disease and sudden death/resuscitated sudden death in pediatric heart transplant recipients.

BACKGROUND: Transplant coronary artery disease (TCAD) is a common sequela of heart transplantation. Symptom complexes associated with TCAD have not been well described. The purpose of this study was to determine if somatic complaints are associated with TCAD in pediatric heart transplant recipients. METHODS: We reviewed the medical records of all patients who underwent heart transplantation at our institution from November 1984 to December 2000. TCAD was defined as any interval narrowing of coronary arteries by angiography since the previous study or at least 50% luminal obstruction of 1 or more coronary arteries by histologic examination of explanted or autopsied hearts. RESULTS: Ninety-nine patients received heart transplants, and follow-up data were available in 80. Sixty-six patients met study criteria. Complaints of abdominal (82%), chest (45%), abdominal and chest (27%), and arm (9%) pain were made by 22 (33%) of 66 patients, and TCAD was present in 27 (41%). Of the 22 patients with pain, TCAD was present in 18, for a positive predictive value of 82% (95% confidence interval [CI] 60%-95%). The relative risk of TCAD being present in patients with a history of pain was 4 times that of patients without pain (p < 0.001). Sudden death or resuscitated sudden death occurred in 15 (68%) of 22 patients with pain vs 4 (9%) of 44 without pain (p < 0.001). CONCLUSIONS: The symptom complex of abdominal, chest and/or arm pain is strongly associated with the presence of TCAD and sudden death or resuscitated sudden death in pediatric heart transplant recipients.

Abdominal Pain↗