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Pancreas transplant outcomes for United States (US) cases reported to the United Network for Organ Sharing (UNOS) and non-US cases reported to the International Pancreas Transplant Registry (IPTR) as of October, 2000.

As of October 2000, > 15,000 pancreas transplant had been reported to the IPTR, > 11,000 in the US and > 4,000 outside the US. An era analysis of US cases from 1987-2000 showed a progressive improvement in outcome (p < 0.04), with pancreas transplant graft survival rates (GSRs) going from 72% to 82% at one year for SPK cases, from 52% to 74% for PAK cases, and from 47% to 76% for PTA cases. The improvements were due both to decreases in technical failure (TF) rates (overall from 16% to 7%) and immunological failure rates (going from 8% to 2% for SPK, from 27% to 6% for PAK, and from 37% to 12% for PTA cases). The proportion of recipients > 45 years old increased from 5% to 25%, and the improved outcomes encompassed the older patients as well. In patients > 45 years old, SPK pancreas GSRs at one year increased from 62% to 78% (p < 0.002). Pancreas GSRs were also similar for recipients reported to have Type 1 or Type 2 diabetes (at one year, 84% and 83%, respectively for 1996-2000 SPK transplants), the latter designated in 3% of the recipients. Contemporary pancreas transplant outcomes were calculated separately for 1996-2000 US and non-US cases. US patient survival rates at one year were > or = 94% in each recipient category, with one-year pancreas GSRs of 84% for SPK (n = 3,697), 76% for PAK (n = 696), and 71% for PTA (n = 300) (p = 0.0001). The immunological graft failure rates for 1996-2000 US SPK, PAK and PTA cases were 2%, 6%, and 8% at one year (p = 0.001). There was a progressive increase in the use of ED (as opposed to BD) for duct management, to > 50% for 1996-2000 US SPK transplants. Approximately 20% of US SPK ED transplants had venous drainage via the portal system. Pancreas GSRs were not significantly different for 1996-2000 ED (n = 1,940) and BD (n = 1,541) US SPK transplants (83% and 84%, respectively, at one year), nor was there a difference in pancreas GSRs for systemic (n = 1,509) versus portal (n = 411) venous drained ED SPK transplants (83% for both at one year). Kidney GSRs were also not significantly different for ED versus BD US SPK cases, 93% versus 91% at one year (p = 0.13). Duct management did matter for solitary (PAK and PTA) pancreas transplants (P < or = 0.07). Pancreas GSRs for PAK recipients were 77% at one year for BD (n = 359) versus 67% for ED (n = 306) US transplants; for PTA 75% (n = 174) versus 63%. However, BD transplants were associated with a 12% conversion rate to ED by 2 years after transplantation. Analyses of outcome by immunosuppression for US cases showed pancreas GSRs ranged from 77% to 88% at one year, but were highest in SPK recipients given anti-T-cell agents for induction and CSA-MMF for maintenance immunosuppression. For PAK and PTA recipients, those given anti-T-cell agents for induction and TAC-MMF for maintenance immunosuppression had the highest GSRs: 78% and 78%, respectively, at one year for BD pancreas transplants (vs. 85% in BD SPK recipients similarly immunosuppressed, P > 0.08). In regard to non-US cases, the overwhelming majority were in the SPK category (n = 676 for 1996-2000), with a one-year pancreas GSR of 84%, not significantly different than for US cases. In summary, pancreas transplant graft survival rates were > 70% in the solitary (PAK and PTA) and > 80% in SPK recipients during the last 4 years of the 20th century. These outcomes culminate a third of a century of application for the treatment of diabetes mellitus.

Adult↗

Analysis of United States (US) and non-US pancreas transplants reported to the United network for organ sharing (UNOS) and the international pancreas transplant registry (IPTR) as of October 2001.

As of October 10, 2001, > 17,000 pancreas transplant had been reported to the IPTR, > 11,500 in the US and > 4,700 outside the US. An era analysis of US cases from 1987 to 2001 showed a progressive improvement in outcome (p < 0.04), with pancreas transplant graft survival rates (GSRs) going from 75% to 83% at one year for SPK cases, from 50% to 78% for PAK cases, and from 49% to 78% for PTA cases. The improvements were due both to decreases in technical failure (TF) rates (from 14% to 7% in SPK, 23% to 8% in PAK, and 23% to 10% in PTA) and immunological failure rates (going from 7% to 2% for SPK, from 25% to 2% for PAK, and from 28% to 4% for PTA cases). The proportion of recipients > 45 years old increased from 5% to 25%, and the improved outcomes encompassed the older patients as well. In patients > 45 years old, SPK pancreas GSRs at one year increased from 74% to 80% (p < 0.007). Pancreas GSRs were also similar for recipients reported to have Type 1 or Type 2 diabetes (at one year, 84% and 83%, respectively for 1997-2001 SPK transplants), the latter designated in 5% of the recipients. Contemporary pancreas transplant outcomes were calculated separately for 1997-2001 US and non-US cases. US patient survival rates at one year were > or = 95% in each recipient category, with one year pancreas GSRs of 83% for SPK (n = 3885), 79% for PAK (n = 630), and 78% for PTA (n = 240) (p = 0.0002). The immunological graft failure rates for 1997-2001 US SPK, PAK and PTA cases were 4%, 6%, and 8% at one year (p = 0.0001). There was a progressive increase in the use of ED (as opposed to BD) for duct management, to 67% for 1997-2001 US SPK transplants, 51% for PAK and 42% for PTA. Of US SPK ED transplants, 22% had venous drainage via the portal system. US pancreas GSRs were not significantly different for 1997-2001 ED (n = 2,519) and BD (n = 1,260) US SPK transplants (82% and 85%, respectively, at one year), nor was there a difference in pancreas GSRs for systemic (n = 1,958) versus portal (n = 557) venous-drained ED SPK transplants (82% vs. 84% at one year). Kidney GSRs were slightly higher for ED versus BD US SPK cases, 93% versus 91% at one year (p = 0.03). Duct management did matter for solitary (PAK and PTA) pancreas transplants. Pancreas GSRs for PAK recipients were 85% at one year for BD (n = 316) versus 74% for ED (n = 303) US transplants (p < 0.02); for PTA 81% (n = 168) versus 74% (p > or = 0.37). However, BD transplants were associated with a 12% conversion rate to ED by two years posttransplant. Recipient age made little difference for outcome in any category. Indeed, in the PTA category GSRs were significantly higher for US recipients > 45 years old (n = 66) than 21-45 years old (n = 216), 85% versus 77% at 1 year (p < or = 0.10). TAC + MMF was the dominant maintenance immunosuppressant for 1999-2001 US cases (> 70%). In an analysis of outcome according to type of anti-T-cell antibody agents (depleting vs. non-depleting vs. none) for induction therapy in TAC + MMF treated recipients, there were no differences in GSRs in any of the categories. In regard to non-US cases, the overwhelming majority were in the SPK category (n = 1,649 for 1997-2001), with a one year pancreas GSR of 82%, not significantly different than for US cases. In summary, pancreas transplant graft survival rates were nearly 80% at one year in recipients of solitary (PAK and PTA) pancreas transplants, and > 80% in SPK recipients for 1997-2001 cases. The outcome continues to improve as increasing numbers of solitary pancreas transplants are done.

Adult↗

Middle East Society for Organ Transplantation (MESOT) Transplant Registry.

During the seventies, sporadic renal transplants were performed in few MESOT-region countries, mainly Turkey, Iran, Egypt, and Lebanon. Since the introduction of cyclosporine in the early eighties, transplantation has become the preferred therapeutic modality for end-stage renal failure. In 1986, the Islamic theologians (Al Aloma) issued what became known as the Amman declaration, in which they accepted brain death and retrieval and transplantation of organs from living and cadaveric donors. Based on this and similar declarations, all Middle Eastern countries except Egypt passed laws that allow cadaveric transplantation and regulate live donations. Iran, Turkey, Saudi Arabia, Kuwait, Tunisia, Jordan, and Lebanon all have current active cadaveric programs and perform liver, heart, pancreas, and lung transplants. More than 5088 renal transplants/year are performed in the region with Iran leading with 1600. The cumulative number of renal transplant patients is now nearly 60,000. With a 2003 population of 600,682,175, the rate/million for renal transplantation in the MESOT region is a mere 9/million. Rates of renal transplantation range from 31/million in some countries to 0 in others. The major obstacle in establishing an accurate number of transplants is "tourist transplantation," in which the same transplanted patients are registered in different countries. Although cadaveric programs have been active for more than 10 years, live-related and nonrelated transplants account for nearly 85% of the total transplants. The data presented were collected from MESOT representatives in the region and from publications. For proper compilation of the registry, a format is being proposed that will be presented at the Congress for review and adaptation. Even with the limited resources in the region, immunosuppressive drugs for induction and maintenance therapy are available and are used. Costs for transplantation and immunosuppressive therapy are either totally or heavily supported by governmental agencies.

Humans↗

Early recognition of heart transplant rejection by backscatter analysis from serial 2D ECHOs in a heterotopic transplant model.

The acute phase of heart transplant rejection was evaluated with two-dimensional echocardiographic (2D ECHO) image analysis in a modified Mann's cervical heterotopic transplant. Serial 2D ECHO images were obtained daily, and myocardial biopsies were obtained on the day of transplant, on day 3 after transplant, and after total rejection. Brightness of serial 2D myocardial ECHO images significantly increased to day 3 after transplant, indicating increased backscatter during hyperacute rejection. Histologically this was associated with myocardial edema. These results suggest a potential noninvasive means of recognizing acute cardiac rejection. Heart transplant rejection is characterized by myocardial edema during the early stages. Myocardial edema resulting from ischemia increases the backscatter of ultrasound, which is seen as increased brightness on 2D ECHOs. Hence we hypothesized that myocardial edema observed histologically during a hyperacute rejection process can be seen on serial 2D ECHOs of the transplanted heart. Serial 2D ECHOs were obtained in five goats that had undergone a modified Mann's cervical heterotopic transplant. Image parameters were kept constant throughout each experiment. After each experiment, 2D ECHOs of a soft-tissue phantom were also recorded with the same image parameters and were used for normalizing the myocardial brightness estimated from 2D ECHO images. Visually, brightness of 2D ECHO images of all transplanted myocardia increased to day 3 after transplantation; thereafter, the brightness decreased but was still greater than on the day of transplantation. The measured mean (+/- SD) relative integrated brightness increased from 0.60 +/- 0.38 on the day of transplantation to 1.05 +/- 0.43 (p less than 0.005) on day 3 after transplantation and decreased to 0.70 +/- 0.33 (p less than 0.05) on day 7 after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Relapse after non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: early transplantation, use of an unrelated donor, and chronic graft-versus-host disease are protective.

We analyzed the incidence of posttransplant chronic myelogenous leukemia (CML) relapse in 283 consecutive related-donor (n = 177) and unrelated-donor (n = 106) allogeneic transplant recipients. Twenty-two of 165 related-donor recipients with stable or advanced disease at the time of transplant had hematologic relapse of CML following transplant (5-year Kaplan-Meier estimate of relapse, 20%; 95% confidence interval [CI], 11 to 30%). One of 12 patients transplanted in second stable phase following blast crisis also relapsed. Fifteen related-donor transplant recipients relapsed within 5 years of transplant; however, seven relapsed between 5 and 9 years after transplant. Factors independently associated with an increased risk of posttransplant relapse for related-donor recipients included prolonged interval between diagnosis and transplant (relative risk, [RR], 3.81; P = .009) and bone marrow basophilia (RR, 5.62; P = .01). Related-donor recipients with posttransplant chronic graft-versus-host disease (CGVHD) had a decreased risk of relapse (RR, 0.24; P = .005). Only two of 106 unrelated-donor transplant recipients relapsed following transplant (5-year Kaplan-Meier estimate of relapse, 3%; 95% CI, 0% to 7%). When both related- and unrelated-donor recipients were considered, the use of an unrelated donor was independently associated with a decreased risk of relapse (RR, 0.24; P = .07). Twelve of 16 relapsing patients who received further therapy (nine of 13 who underwent second transplant and three of three who received donor leukocyte infusions) remain alive. This analysis shows that relapse, sometimes occurring long after transplant, is an important adverse outcome in allogeneic transplantation for CML. Early transplant, posttransplant CGVHD, and use of an unrelated donor are associated with a reduced incidence of relapse, perhaps due to allogeneic disparities enhancing the graft-versus-leukemia effect.

Adolescent↗

Hematopoietic stem cell transplantation in childhood: report from the bone marrow transplantation group of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

BACKGROUND AND OBJECTIVE: Transplantation of hematopoietic stem cells from different sources is being increasingly used to treat a variety of diseases in children. Transplant procedures and indications have changed considerably during recent years. Monitoring of information about these changes is useful for interpretation of nationwide collected data. DESIGN AND METHODS: Since 1985, Centers belonging to the AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica), performing hematopoietic stem cell transplants (HSCT) in children, and members of the AIEOP-Bone Marrow Transplant (BMT) Group annually report data on their transplant activity to the AIEOP-BMT Registry employing specially prepared patient-oriented forms. RESULTS: From January 1985 to December 1998, a total of 2,474 bone marrow (BM), peripheral blood (PB) or umbilical cord blood (CB) transplants were reported: 1,296 (52%) were allogeneic (Allo) and 1,178 (48%) autologous (Auto) transplants. These transplants were performed in 19 Italian Centers on 2,249 patients aged less than 17 years. Among Allo-transplants, 1,198 (92%) were performed using BM progenitor cells, whereas 49 (4%) CB, 42 (3%) were PB, 4 BM plus PB, and 3 BM plus CB allografts; they were performed using HLA-identical sibling donors in 867 cases (67%) and alternative donors (i.e. partially-matched relatives or unrelated donors) in the remaining 429 (33%) cases. Allogeneic transplants were performed on 786 (67%) patients with malignancy and on 395 (33%) patients with non-malignant disorders. In the last 6 years, the number of Allo-transplants per year exceeded that of Auto-transplants. Of the Auto-transplants, 775 (66%) were performed using BM, and 403 (34%) using PB alone or combined with BM hematopoietic stem cells. Indications for Auto-BMT were myelo-lymphoproliferative disorders in 524 (49%) cases, solid tumor in 533 (50%) cases and non-malignant disease in 11 (1%) cases. In the last 5 years, the use of PB for autografts has increased from 7% to 70%. INTERPRETATION AND CONCLUSIONS: These data reflect the development and present status of HSCT in Italy and provide a basis for patient counseling and health care planning.

Adolescent↗

Transplantation of embryonic occipital cortex to the brain of newborn rats. An autoradiographic study of transplant histogenesis.

The neurogenesis of immature cerebral cortex transplants was investigated using tritiated thymidine (3HT) autoradiography. Cortical tissue taken from rat fetuses during their last week of gestation (E15-E21) was transplanted to the tectum or cerebral cortex of newborn rat hosts. At different times after transplantation, a single injection of 3HT was given to the host. Most of the experimental animals were killed after the transplants had grown to maturity (5-12 weeks), and some were studied shortly after the tracer had been given. In other experiments, donor tissue was used that was labeled in utero up to 1 day before being transplanted on E16, E17, E18, or E19. It was found that neurons labeled before transplantation survived and differentiated in the graft. Removal of the graft from its natural context did not prevent 3HT incorporation into surviving precursor neurons, indicating continuation of neurogenesis in the cortical transplants. In transplants from E16 donors neurons continued to be generated for 5-6 days after transplantation. Termination of neurogenesis occurred at successively earlier times in transplants taken from correspondingly older embryos. Independent of size and position of the transplant, application of 3HT after "projected" transplant ages of E23 and older labeled only nonneuronal cells. This suggests a time schedule of neuron generation in the cortical transplants similar to that observed during normal development of the cerebral cortex, which is not disturbed by the transplanting procedure.

Animals↗

Surveillance for transplant coronary artery disease in infant, child and adolescent heart transplant recipients: an intravascular ultrasound study.

BACKGROUND: Transplant coronary arteriopathy (TCAD) limits graft survival after heart transplantation in adult and pediatric heart transplant recipients. Intravascular ultrasound (IVUS) provides a highly sensitive technique to detect TCAD. However, its use to determine factors associated with TCAD in pediatric recipients has been limited and its utility in surveillance for symptomatic TCAD in this population is uncertain. METHODS: One hundred fifty-eight IVUS studies from 66 patients (27 <1 year and 39 >1 year at time of transplant) were performed 12 to 144 months after transplantation within the routine surveillance for TCAD. Maximal intimal thickness (MIT) and intimal index (II) were measured, and the Stanford classification was utilized to grade overall severity of disease. Mixed repeated-measures linear regression models were used to investigate the main and interaction effects of age at transplant, age at time of study, time since transplant and rejection events. RESULTS: Age at catheterization (p = 0.0002), transplantation at age >12 months (p = 0.014), increasing time after transplantation (p = 0.021) and the combination of late rejection and hemodynamic compromising rejection (p = 0.05) were significantly associated with increasing MIT. Age at catheterization (p = 0.0149), transplantation at age >12 months (p = 0.016), time from transplantation (p = 0.0076) and rejection with hemodynamic compromise (p = 0.01) were significantly associated with increased II. Nine patients developed evidence of severe (Stanford Class 4) TCAD by IVUS, but only 2 (22%) developed symptomatic TCAD, with a median follow-up of 44 months. Four of the 7 patients who developed symptomatic TCAD had no or minimal TCAD (Stanford Class 0 or 1) on a surveillance examination within 18 months of the onset of symptoms. CONCLUSIONS: Increasing time after transplantation, recipient age and age at transplantation as well as rejection history, especially rejection with hemodynamic compromise, are associated with the development of TCAD as detected by IVUS in pediatric heart transplant recipients. Severe TCAD detected by IVUS does not often rapidly progress to symptomatic TCAD. Symptomatic TCAD may develop rapidly even in patients with little or no TCAD detected by IVUS.

Adolescent↗

Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

BACKGROUND: Transplantation of blood or bone-marrow stem cells is the treatment of choice for selected patients with chronic myeloid leukaemia (CML). Transplantation is used with increasing frequency and success, but remains associated with substantial risks of morbidity and mortality. Other treatments with satisfactory short-term outcome are available. For appropriate counselling of patients, a rapid and simple way to assess risk is needed. METHODS: Data from 3142 patients (1873 [60%] male, 1269 [40%] female; mean age 34 years, range <1-60 years) treated with allogeneic blood or marrow transplants for CML between 1989 and 1997, reported to the European Group for Blood and Marrow Transplantation (EBMT), were used to develop and test a simple risk score based on previously reported major pretransplant risk factors: histocompatibility, stage of disease at time of transplantation, age and sex of donor and recipient, and time from diagnosis to transplantation. We analysed probabilities of survival, leukaemia-free survival, transplant-related mortality, and relapse incidence with respect to these risk factors. FINDINGS: At the time of analysis, 1922 (61%) of the 3142 patients were alive-1567 (65%) of those with HLA-identical sibling donors and 417 (57%) of those with unrelated donors. 1682 (54%) were alive without relapse. 1220 (39%) patients had died, 1013 (83%) of transplant-related causes, 207 (17%) of relapse. 447 (14%) patients had relapsed. The final scoring system was highly predictive for leukaemia-free survival, survival and transplant-related mortality. Survival at 5 years was 72%, 70%, 62%, 48%, 40%, 18%, and 22% for patients with scores 0, 1, 2, 3, 4, 5, and 6, respectively. Risk of transplant-related mortality was 20%, 23%, 31%, 46%, 51%, 71%, and 73%. Data showed the same trends for HLA-identical sibling transplants and unrelated transplants for transplants done in 1989-93 and 1994-96. INTERPRETATION: Pretransplant risk factors are cumulative for individual patients with CML having blood or marrow transplantation. A simple system based on five main factors gives adequate risk assessment for counselling of patients and taking decisions.

Adolescent↗

Does human leukocyte antigen matching influence the outcome of lung transplantation? An analysis of 3,549 lung transplantations.

BACKGROUND AND OBJECTIVE: Human leukocyte antigen (HLA) compatibility has been shown to improve the outcome of renal and cardiac transplantation. However, its impact on outcome following lung transplantation is not clear, with several single-center studies reporting inconsistent results. We studied the influence of HLA matching on survival and the development of rejection and obliterative bronchiolitis after lung transplantation, using data from the United Network for Organ Sharing/International Society for Heart and Lung Transplantation registry. METHODS: The study population included adult patients who received cadaveric lung transplants between October 1987 and June 1997 for whom HLA data were available. Two cohorts were examined, depending on the era of transplantation: (1) October 1987 to June 1997 (n = 3,549): Differences in actuarial survival as stratified by either the total number of HLA mismatches or the number of mismatches at each HLA locus were determined using a log-rank test. Multivariate logistic regression models were developed to determine independent predictors of survival at 1, 3, and 5 years following lung transplantation. (2) April 1994 to June 1997 (n = 1,796): The association of HLA mismatching with acute rejection and obliterative bronchiolitis was determined using a chi-squared analysis. RESULTS: Only 164 patients (4.6%) received lung grafts with 2 or fewer HLA mismatches. Univariate analyses demonstrated a significant difference in post-transplant survival by mismatch level, with the total number of HLA mismatches (p = 0.0008) and mismatching at the HLA-A locus (p = 0.002) associated with worse survival. Multivariate logistic regression demonstrated that the number of mismatches at the HLA-A and HLA-DR loci predicted 1-year mortality (incremental odds ratios 1.18, p = 0.01, and 1.15, p = 0. 03, respectively). The total number of HLA mismatches predicted 3- and 5-year mortality (incremental odds ratios 1.13 at 3 years, p = 0. 0004, and 1.14 at 5 years, p = 0.0002). However, other covariates such as repeat transplantation, transplantation for congenital heart disease, advanced recipient age, and an early era of transplantation were stronger predictors of mortality. We found no significant association between HLA mismatching and the development of obliterative bronchiolitis, although there was an association between mismatching at the HLA-A locus and acute rejection episodes requiring hospital admission (p = 0.008). We also found no association between mismatching at the HLA-B locus and rejection episodes requiring either hospitalization or the alteration of anti-rejection medications (p = 0.034). CONCLUSION: Although the number of HLA mismatches at the HLA-A and HLA-DR loci predicted 1-year mortality and the total number of mismatches predicted 3- and 5-year mortality following lung transplantation, the effect of each covariate was small in this multicenter study of 3,549 patients. Further close follow-up of registry patients is necessary to determine the effect of HLA matching on long-term survival and freedom from obliterative bronchiolitis and rejection following lung transplantation. A prospective study of HLA matching for lung transplantation should not yet be considered in view of the small number of grafts with 2 or fewer mismatches and the modest effect of HLA matching on outcome.

Adult↗

Predictability and other aspects of post-transplant diabetes mellitus in heart transplant recipients.

BACKGROUND: Diabetes mellitus that develops after organ transplantation may predispose patients to further complications. We studied the value of pre-transplant oral glucose tolerance testing or maximum random plasma glucose, and HLA-DR3 and/or DR4 phenotype as predictors of post-transplantation diabetes mellitus in heart transplant recipients. PATIENTS AND METHODS: In 228 cardiac allograft recipients (median age, 50 years; mean follow-up, 4.77 years), we used either pre-transplant oral glucose tolerance testing results (Group I, n = 141)-excluding patients with pre-existing diabetes (n = 9)--or maximum random plasma glucose values (Group II, n = 78) to study predictability of post-transplant diabetes. In addition, we investigated its relation to rejection treatment and clinical course. RESULTS: Cumulative incidence of post-transplant diabetes (n = 43) was 19.6%, 83% of which became manifest within 3 months post-transplant; pre-transplant body mass index was higher (p < 0.01) in this group. Mortality did not increase. Of 123 patients in Group I who survived > 3 months, post-transplant diabetes occurred in 32% vs 16% of those with impaired and normal glucose tolerance respectively (ns), and in 55% of patients with isolated post-load hyperglycemia (p < 0.05 vs normal). Maximum random glucose values (Group II) did not predict post-transplant diabetes. Prevalence of the HLA-DR3, DR4, and DR3DR4 phenotypes did not increase in post-transplant diabetes; relation to rejection treatment was likely in 30%. Approximately 50% of posttransplant diabetes patients required only temporary drug treatment. CONCLUSIONS: The risk of post-transplant diabetes increased parallel to pre-transplant degree of glucose intolerance, but was considerable even in normal glucose tolerance. HLA-DR3 and/or DR4 phenotype was not a predisposing factor.

Adult↗

Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management.

BACKGROUND: Invasive aspergillosis is a serious opportunistic infection in lung transplant recipients. It has not been fully discerned whether there are differences in the characteristics, risk factors and outcome of Aspergillus infection in single as compared with bilateral lung transplant recipients. METHODS: English-language articles identified by a MEDLINE search through December 2000 and bibliographies were used as data sources to identify cases of Aspergillus infections in lung transplant recipients. The studies selected had to have provided a definition of invasive aspergillosis to distinguish colonization from infection. RESULTS: The median incidence of Aspergillus infections in lung transplant recipients was 6.2%. In total, 58% (45 of 78) of the Aspergillus infections were tracheobronchitis or bronchial anastomotic infections, 32% (25 of 78) were invasive pulmonary, and 22% (25 of 78) were disseminated infections. Single lung transplant recipients with Aspergillus infections were significantly older (p = 0.006), more likely to have had chronic obstructive pulmonary disease as an underlying illness (p = 0.05), more likely to have developed Aspergillus infections later after transplantation (p = 0.019), and tended to have a higher incidence of invasive aspergillosis (p = 0.11) than all other lung transplant recipients. Overall mortality in lung transplant recipients with Aspergillus infections was 52%. Single lung transplant recipients (p = 0.03), and patients with late-onset infections (occurring at least 3 months after transplantation ([p = 0.045]) infections had significantly higher mortality. CONCLUSIONS: Single lung transplant recipients with Aspergillus infections had an overall greater morbidity and poorer outcome than other types of lung transplant recipients. Recognition of the unique characteristics of Aspergillus infections in single lung (vs bilateral or heart-lung) transplant recipients has implications relevant for the management of lung transplant recipients with aspergillosis.

Aspergillosis↗

Intestinal transplantation: 1997 report of the international registry. Intestinal Transplant Registry.

BACKGROUND: Small bowel transplantation is an evolving procedure. We reviewed the world experience since 1985 to determine the current status of this procedure. METHODS: All of the known intestinal transplant programs were invited to contribute to an international registry using a standardized report form. RESULTS: Thirty-three intestinal transplant programs provided data on 273 transplants in 260 patients who were transplanted on or before February 28, 1997. The number of procedures per year has increased at a linear rate since 1990, with 58 transplants performed in 1996. Two-thirds of the recipients were children or teenagers. The short gut syndrome was the most common indication for transplantation. The types of transplants included the small bowel with or without the colon (41%); the intestine and liver (48%); and multivisceral grafts (11%). The 1-year graft/patient survival for transplants performed after February 1995 was 55%/69% for intestinal grafts; 63%/66% for small bowel and liver grafts; and 63%/63% for multivisceral grafts. Transplants since 1991 and programs that had performed at least 10 transplants had significantly higher graft survival rates. Seventy-seven percent of the current survivors had stopped total parenteral nutrition (TPN) and resumed oral nutrition. CONCLUSIONS: Transplantation has become a lifesaving procedure for (1) patients with intestinal failure who cannot be maintained on total parenteral nutrution and (2) patients who require abdominal evisceration to completely remove locally aggressive tumors. The 5-year survival rate of intestinal transplantation with large series is comparable to lung transplantation.

Adolescent↗

Increased arterial stiffness in cyclosporine-treated lung transplant recipients early after transplantation.

BACKGROUND: The majority of patients undergoing solid organ transplantation develop hypertension, to which cyclosporine (CsA)-induced peripheral vasoconstriction may contribute. We hypothesized that CsA-treated transplant recipients have an increased basal vascular tone and an altered response to nitric oxide. To test this hypothesis arterial resistance, non-endothelial dependent relaxation and arterial stiffness were investigated in CsA-treated lung transplant recipients within 18 months after transplantation. METHODS: In study 1, forearm blood flow (FBF) was measured by venous occlusion plethysmography at baseline and during glyceryl trinitrate (GTN) and N(G)-monomethyl-l-arginine acetate (l-NMMA) infusion in seven lung transplant recipients and nine healthy subjects. In study 2, arterial stiffness in carotid (CCA) and radial artery (RA) was measured by ultrasound (echo-tracking) in 10 lung transplant recipients, 12 healthy subjects and six patients waiting for lung transplantation. RESULTS: Basal FBF (3.1 +/- 0.2 vs. 3.0 +/- 0.3 mL/min, p = 0.79) and forearm arterial resistance (36 +/- 3 vs. 33 +/- 3 mmHg/mL/min, p = 0.60) did not differ between transplant recipients and controls. GTN infusion increased and l-NMMA decreased blood flow equally in both groups. Transplant recipients had increased arterial stiffness compared to both pre-transplant patients and healthy subjects (CCA stiffness index 11.7 +/- 1.1 vs. 8.5 +/- 0.2 and 8.6 +/- 0.6, p < 0.05 both; RA stiffness index 14.7 +/- 1.5 vs. 8.9 +/- 1.3 and 10.6 +/- 0.7, p < 0.05 both). CONCLUSIONS: Forearm blood flow and arterial resistance did not differ between healthy subjects and cyclosporine-treated lung transplant recipients early after transplantation. Increased arterial stiffness was demonstrated in transplant recipients, which may have implications for future development of transplant hypertension.

Adult↗

Proteinuria in pediatric renal transplant recipients during the first 60 post-transplant days.

Although normative values of post-transplant proteinuria have been reported in adults, data for pediatric renal transplant recipients have not been previously published. We hypothesized that pediatric renal transplant recipients achieve normal urinary protein to creatinine (UProt/UCr) ratios (<0.2) by 60 days post-transplant in the absence of early recurrent disease. Retrospective chart review of 108 consecutive pediatric renal transplant recipients at Stanford University was performed. Thirty-two (30%) patients who were eligible had > or = 1 UProt/UCr ratio obtained during the first 60 post-transplant days. Mean age at transplant was 13.9 +/- 4.2 yr. UProt/UCr ratios were grouped by week post-transplant for quantile analysis. Mean weekly UProt/UCr values were not lower than 0.2 until the ninth post-transplant week. No difference in post-transplant proteinuria existed between nephrectomized and non-nephrectomized transplant recipients. Experience with a single patient with proven focal segmental glomerulosclerosis (FSGS) recurrence suggests that normative UProt/UCr data may be useful in early identification of patients experiencing disease recurrence. Univariate correlations demonstrated that UProt/UCr negatively correlated with serum albumin levels (-0.415, p < 0.0001) and days post-transplant (-0.531, p < 0.0001). Independent of primary diagnosis, proteinuria persists throughout the first 60 days in most pediatric renal transplant patients, decreasing relative to time post-transplant.

Adolescent↗

A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome.

Bone marrow transplantation (BMT) can cure myelodysplastic syndrome (MDS), although transplantation carries significant risks of morbidity and mortality. Because the optimal timing of HLA-matched BMT for MDS is unknown, we constructed a Markov model to examine 3 transplantation strategies for newly diagnosed MDS: transplantation at diagnosis, transplantation at leukemic progression, and transplantation at an interval from diagnosis but prior to leukemic progression. Analyses using individual patient risk-assessment data from transplantation and nontransplantation registries were performed for all 4 International Prognostic Scoring System (IPSS) risk groups with adjustments for quality of life (QoL). For low and intermediate-1 IPSS groups, delayed transplantation maximized overall survival. Transplantation prior to leukemic transformation was associated with a greater number of life years than transplantation at the time of leukemic progression. In a cohort of patients under the age of 40 years, an even more marked survival advantage for delayed transplantation was noted. For intermediate-2 and high IPSS groups, transplantation at diagnosis maximized overall survival. No changes in the optimal transplantation strategies were noted when QoL adjustments were incorporated. For low- and intermediate-1-risk MDS, delayed BMT is associated with maximal life expectancy, whereas immediate transplantation for intermediate-2- and high-risk disease is associated with maximal life expectancy.

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Liver transplantation in the United States from 1987-1998: updated results from the Pitt-UNOS Liver Transplant Registry.

CENTERS: Between 1988-1997, the total number of liver transplantations performed in the US more than doubled from 1,713-4,158, and the number of centers performing liver transplantations increased from 59-107. In recent years, the yearly net gain in the number of operating centers has slowed, and the differences in LT volume across centers has remained stable. OUTCOMES: During the first year following transplantation, patient survival was approximately the same for adults and children, while retransplantation-free survival was poorest among children. Thereafter, survival declined more rapidly among adults than among children. SURVIVAL AMONG PEDIATRIC RECIPIENTS: The estimated cumulative probability of a pediatric recipient surviving for 10 years following transplantation was .80, and surviving for 10 years without retransplantation was .59. In general, few deaths or retransplantations were observed more than 4 years after the initial transplantation. Factors independently associated with patient and retransplantation-free survival among children were year of transplantation, recipient age, being on life support while awaiting transplantation, primary liver disease, serum creatinine, total bilirubin, donor age, donor race, and warm ischemic time. Recipient race, a multi-organ transplant procedure, and serum albumin level were significantly associated with patient survival only. The use of a reduced-size or split liver for transplantation in children was independently associated with retransplantation-free survival, but not with patient survival. SURVIVAL AMONG ADULT RECIPIENTS: The estimated cumulative probability of an adult recipient surviving for 10 years following transplantation was .61, and surviving for 10 years without retransplantation was .46 with the median retransplantation-free survival time estimated at 9.2 years. Factors independently associated with patient and retransplantation-free survival among adults were year of transplantation, recipient age, recipient race, recipient location awaiting transplantation, primary liver disease, serum creatinine and albumin levels, hepatitis B surface antigen status, donor age, donor anti-CMV status, warm ischemic time, sex match, pretransplant ventilator or inotrope use, and recipient anti-HCV status. Pre-transplant bilirubin level, a multi-organ transplant procedure, and the finding of an incidental tumor were significantly associated with patient survival; and donor race, ABO match, and uncontrolled variceal bleeding were associated with retransplantation-free survival.

Adolescent↗

Liver transplantation in the United States: a report from the UNOS Liver Transplant Registry.

Transplants and centers Between 1988 and 1998 the number of liver transplants performed in the US more than doubled from 1,713 to 4,487; the number of centers increased from 59 to 116. The number of living donor, segmental, and multiple organ transplants also increased over time. The rate of increase in the number of centers has slowed over the last few years. Outcomes. Survival among pediatric recipients. The one- and 7-year graft survival rates for pediatric recipients were 72% and 62%, respectively. The one- and 7-year patient survival rates were 85% and 79%. Patient survival did not decrease much after the first 2 years and graft survival stabilized after 4 years posttransplant. Some of the factors associated with increased odds of graft failure and patient death at 6 months posttransplant included having a previous transplant; being hospitalized, in the ICU, or on life support at the time of transplant; creatinine > 2 mg/dl; donor age and race/ethnicity; and transplant type. Factors associated with decreased odds of graft failure or patient death were recipient gender, recipient race/ethnicity, having a metabolic disease and receiving a living donor liver. Among grafts/recipients surviving the first 6 months after transplantation, recipient race/ethnicity, primary liver disease, having a previous transplant, donor age and race/ethnicity, and transplant type were associated with a greater relative risk of graft failure and mortality. Survival among adult recipients. The one- and 7-year graft survival rates among adult recipients were 77% and 57%, respectively. The one- and 7-year patient survival rates were 85% and 67%. Survival rates decreased steadily at all time points following transplantation. Some of the factors associated with increased odds of graft failure and mortality at 6 months after transplantation were recipient age and race/ethnicity; primary liver disease; having a previous transplant; being hospitalized, in the ICU, or on life support at the time of transplant; longer cold ischemia time; older donor age, race/ethnicity, or gender; and having a non-identical recipient/donor blood type match. Having cholestatic liver disease/cirrhosis and shorter cold ischemia times were associated with decreased odds of graft failure and mortality. Many of these characteristics also affected grafts and patients surviving the first 6 months, including recipient race/ethnicity, primary liver disease, previous transplant, and donor age.

Adolescent↗