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PubMed1980

[Renocortical oxygen supply after kidney transplantation. Renocortical oxygen supply and kidney circulation after autologous kidney transplantation in the dog; its value for human kidney transplantation].

Determination of the viability of a transplanted kidney is still an unsolved problem. Apart from immunological effects hemodynamic and microcirculatory changes in the kidney are important. Thus in 39 mongrel dogs renal floow flow (electromagnetic and local renocortical oxygen supply) and microcirculation (by meaning local tissue pO2) were determined before nephrectomy, immediately after revascularization and before sacrification in experiments with autologous transplantation. Whole kidney blood flow decreased by 30-40%. Measurements of tissue pO2 revealed distinct changes in renocortical oxygen supply. Graft function concomitantly was reduced. Hypotension during revascularization is followed by a strong decrease in renal blood flow and renocortical oxygen supply. Even short periods of hypotension should be avoided.

Animals↗
PubMed1997

Points to note from indications for heart transplantation to post-heart transplant care: from the care of patients with refractory heart failure and overseas heart transplantation.

To examine important points surrounding the indications for heart transplantation (HTX) to care after HTX, we reviewed 22 patients with refractory heart failure aged less than 60 years who had been observed for the past 6 years. Sixteen patients had dilated cardiomyopathy; 1, dilated hypertrophic cardiomyopathy; 3, restrictive cardiomyopathy; and 2, ischemic cardiomyopathy; there were 15 males and 7 females, and 6 of the 22 patients were children. The 22 patients were divided into two groups according to their response to tailored medical therapy. Group 1 (n = 6) consisted of those whose cardiac function improved to New York Heart Association (NYHA) status 2 from NYHA status 3 or 4. Group 2 (n = 16) still exhibited refractory heart failure. Seven of these 16 patients went on to have successful HTX. Survival in groups 1 and 2 combined was significantly lower than actuarial survival post-HTX cited in the registry of the International Society for Heart and Lung Transplantation, and group 2 had an even lower survival than the total groups 1 and 2 survival. Survival in children was much lower than that in adults. Seven of the 16 patients in group 2 showed a genetic link, but there was no genetic link in group 1 patients. One patient in group 2 had a panel reactive antibody (PRA) value of 46% and died while awaiting HTX. Post-HTX care in terms of immunosuppressant therapy, was modified for each patient. It is particularly necessary to consider the time a patient will wait on the list for candidates for HTX who are children, have a genetic link, or are positive for PRA. A genetic approach is helpful to determine indications for HTX. Sensitive monitoring of post-HTX immunosuppression is needed.

Adolescent↗
PubMed2004

Immunosuppression use in renal transplantation from Asian transplant centers: a preliminary report from the Asian Transplant Registry.

Since the first renal transplant (RTx) in 1956 in Asia in Japan, over 100,000 RTx have been performed in over 300 centers across the region. A survey was conducted to evaluate immunosuppression (IS) use among Asian RTx. Briefly, directors of RTx centers were surveyed regarding IS use for RTx performed at their centers in 2001 for (1) induction therapy, (2) maintenance IS therapy at hospital discharge, (3) antirejection treatment (REJ) to 1 year post-RTx, and (4) maintenance IS therapy to 1 year post-RTx. Categories and types of IS included in the survey were polyclonal antilymphocyte antibodies (PAB), OKT3, IL2 receptor antibodies (IL2RAb), corticosteroids (CS), cyclosporine (CyA), tacrolimus (Tac), azathioprine (Aza), mycophenolate mofetil (MMF), Mizoribine (Miz), Sirolimus (Sir), and other agents. Though only 17 RTx centers in Asia responded to the survey, a wide variation in IS use was demonstrated. In the 334 living and 85 cadavericRTx among whom actual usage was reported, induction therapy was used in only 18.4% of Asian RTx (14.1%, IL2RAb; 4.3%, PAB), in contrast to the 59.3% reported as using induction IS among RTx from the UNOS database in the same year. For maintenance therapy at hospital discharge, 87.1% of Asian RTx received CyA-based IS while only 12.4% received Tac-based therapy. This is in contrast to the 55.3% use of Tac for new RTx in the United States. Generic CyA has widespread use in Asia with over 29.9% on CyA using generic versus the Neoral formulation. Azathioprine is still the predominant antimetabolite in use in Asian RTx, with MMF being used in only 33.6% of patients, in contrast to its 77% usage in the United States. Usage of Tac and MMF for maintenance therapy was significantly higher among cadavericRTx (P < .005). Corticosteroids were used in 51.1% of REJ episodes while PAB or OKT3 were used in 31.9% and 17% of REJ episodes, respectively. As these results may be skewed due to participation of few centers in the survey, greater participation will ensure more accurate evaluation of immunosuppression use in Asia for de novo RTx.

Asia↗
PubMed1998

Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party.

To determine the incidence and outcome of hepatic veno-occlusive disease (VOD) after blood or marrow transplantation (BMT), we prospectively evaluated all consecutive patients receiving a BMT during a 6-month period in participating EBMT centers. All of them were evaluated for occurrence of VOD according to previously defined clinical criteria. The clinical course, outcome, value of prophylactic and therapeutic interventions, and the influence of previously described risk factors were analyzed. During the study period, 1,652 BMT were performed in 73 centers. VOD was diagnosed in 87 patients (5.3%; 95% confidence interval [CI], 4.2% to 6.4%). Fifty-six of 631 allogeneic BMT (8.9%) and 31 of 1,010 autologous BMT (3.1%) developed this complication (P <.0001). VOD was classified as mild in 7 (8%), moderate in 56 (64.4%), and severe in 24 (27.6%) cases. Sixteen patients died of VOD (corresponding to 1% of the whole series, 18.4% of VOD patients, and 66.7% of severe VOD). The use of unfractionated heparin did not significantly decrease the incidence of VOD. Independent variables associated with an increased risk of VOD were allogeneic BMT (relative risk [RR], 2.8; P <.001), pre-BMT elevation of serum aspartate aminotransferase (RR, 2.4; P =.001), high-dose cytoreductive therapy (RR, 2.3; P =.003), Karnofsky performance score less than 90% (RR, 2.7; P =.006), and prior abdominal radiation (RR, 2.9; P =.03). In conclusion, this prospective study shows that (1) the incidence of VOD is lower than that reported in smaller studies from single centers, (2) about one fourth of cases of VOD progress to severe disease, (3) main risk factors have a major impact on incidence of VOD, and (4) the use of prophylactic unfractionated heparin does not seem to reduce the incidence of VOD.

Adult↗
PubMed2002

Cardiac Transplantation: Pre-transplant Infectious Diseases Evaluation and Post-transplant Prophylaxis.

Screening of recipients and donors of cardiac allografts for infectious pathogens, and the use of appropriate immunization and antimicrobial prophylaxis strategies, remain important for the control of infection following heart transplantation. However, the risk of infectious complications in a particular patient must often be weighed against the risk of delaying or denying allograft transplantation. In addition, the ongoing degree of immunosuppression and its contribution to the risk for infectious complications should also be considered to guide the length of prophylactic antimicrobial therapy and provide optimal patient care.

Journal Article↗
PubMed1995

The European Primary Hyperoxaluria Type 1 Transplant Registry report on the results of combined liver/kidney transplantation for primary hyperoxaluria 1984-1994. European PH1 Transplantation Study Group.

This paper reports on a total of 61 patients receiving 64 liver grafts for primary hyperoxaluria type 1 (PH1) at 25 centres throughout Europe between 1984 and 1994 recorded in a central registry. Fifty-seven patients received simultaneous kidney grafts and one patient a delayed kidney graft, two patients received isolated liver grafts and a further three patients underwent retransplantation of the liver, a final patient receiving a liver alone dying intra-operatively before a planned kidney graft was performed. Results of such liver grafts are excellent, reversing the metabolic defect of PH1. Thirteen grafts have been lost and 10 patients have died, with actuarial graft and patient survival rates of 88% at 1 year and patient survival of 80% at 5 years. Early combined liver and kidney grafting appears to represent the optimal treatment for patients with PH1, avoiding the adverse effects of a prolonged period of dialysis and the development of the complications of systemic oxalosis. The registry will continue to collect and collate data on patients undergoing hepatic transplantation for PH1.

Adolescent↗
PubMed2002

European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.5.4. Cardiovascular risks. Post-transplant diabetes mellitus.

GUIDELINES: A. Post-transplant diabetes mellitus (PTDM) should be identified by regular (every 3 months) fasting blood glucose and/or glycated haemoglobin (HbA1c) measurements. PTDM should be treated as appropriate to achieve normoglycaemia. B. Immunosuppressive therapy should be adjusted to reverse or ameliorate PTDM.

Diabetes Mellitus↗
PubMed1998

[Allogenic blood stem cell transplants: characteristics of transplantation material and clinical transplantation course].

We have analysed the clinical course of the 14 consecutive allogeneic peripheral blood stem cell transplantations (PBSCT) and cellular composition of the grafts. Donors were HLA-identical siblings except for the one donor who was only HLA-phenotypically identical brother. Nine of them were sex-mismatched to their recipient. Donors received filgrastim (G-CSF) at a dose of 10 microkilograms/kg for 5 days (4-6). Leukaphereses were started at 5 day to obtain the target dose 4 x 10(6) CD34+ cells/kg recipient weight. Median 24 l of blood (24-36) was processed collecting: 10.3 x 10(8)/kg (6.69-18.8) WBC, 9.9 x 10(8)/kg (5.87-16.02) MNC, 9.72 x 10(6)/kg (0.74-18.98) CD34+ cells, 242.5 x 10(6)/kg (77.9-422) T lymphocytes (CD4+ to CD8+ ratio was 1.5), 76 x 10(6)/kg (24-113) B lymphocytes, 33 x 10(6)/kg (14-88) NK cells and 168.8 x 104/kg (23.1-271.4) CFU-GM with 131.7 x 10(4)/kg (8.4-297.6) BFU-E. Engraftment times to a neutrophil count (ANC) > 0.5 x 10(9)/l was achieved at a median of 15 days (range 10-23) in all patients whereas the platelet count > 20 x 10(9)/l at a median of 14 days (9-19) in all but one patient who received the smallest dose of CD34+ cells. Acute graft versus host disease (GvHD) developed in 8 patients who survived more than 30 days. Most of them (75%) were patients with chronic myeloid leukaemia (CML). In 4 of them GvHD was steroid resistant. Chronic GvHD developed in 3 of 6 evaluable patients. We confirm that allogeneic PBSCT result in rapid and longterm trilineage engraftment. However, the observation of the increasing incidence and severity of acute GvHD in patients with CML will require verification in the larger setting of patients after completion of ongoing clinical trials.

Adult↗
PubMed1984

[Transplant conditioning and transplant size in heterotopic autologous spleen transplantation].

In an experimental study we compared two methods of preparing transplants in rabbits (n = 66): 4-5 splenic fragments with a thickness of 1 mm and graduated weight (5-800 mg) were attached onto the peritoneal peritoneum. Splenic homogenates with increasing weight (5-800 mg) were placed in 4-5 preformed pockets in the parietal peritoneum. At different postoperative intervals (maximum 42 days), a relaparotomy was performed. The regenerated splenic tissue was dissected, weighted and histologically examined. We found a linear correlation between pre- and postoperative weight. However, this correlation applies only to the homogenates with a weight of maximal 200 mg and to the fragments with a weight of maximal 300 mg. We have come to the conclusion that homogenates regenerate better than fragments.

Animals↗
PubMed1995

Survival modelling in kidney transplantation: hazard rates of graft loss. Transplant Working Group of the Registry Committee of the European Dialysis and Transplantation Association-European Renal Association (EDTA-ERA).

Mathematical modelling of survival data provides long-term projection of graft survival and allows evaluation of the impact of several variables on graft outcome. We analysed 52,315 first cadaveric grafts performed between 1971 and 1985 and reported to the EDTA Registry. We quantified the risk of graft loss using the hazard rates. The hazard function provides the magnitude of the risk of graft loss at a given time post-transplantation. For the 1971 and the 1985 cohorts, the risk of graft loss at 1 month posttransplantation was 143 and 53 per 1000 patient-months, respectively. At 1 year it was 5 and 2.4 per 1,000, respectively. The hazard function thus allowed quantification of the magnitude of the risk of graft loss and its evolution along with time. At 5 years posttransplantation, the risk of graft loss was close to 1 per 1,000, whatever the cohort considered, quantifying the lack of improvement of graft losses in the long term since the early 1970s. It was also possible to evaluate the composition of the risk and to explore the respective influence of graft failure and of patient death.

Aged↗
PubMed1996

Transplantation Report. 2: Pre-emptive renal transplantation in adults aged over 15 years. The EDTA-ERA Registry. European Dialysis and Transplant Association-European Renal Association.

Between 1985 to 1992, 2545 renal transplantation (RTx) were performed as pre-emptive grafts in adults. This procedure represented 7.2% of first RTx for patients starting first renal replacement therapy (RRT) during this period, 6.1% of RTx performed in 1992 and 5.6% of all RTx ever performed and reported to the EDTA Registry. The procedure is more frequent in cases of live donor grafts, representing one third of pre-emptive RTx. Both 5 year patient and graft survivals are unaffected by dialysis duration prior to the first RTx: none in pre-emptive, < 1 years, 1-5 years or > 5 years. In our personal view, this procedure should be developed.

Adolescent↗
PubMed1989

[Long-term results of orthotopic liver transplantation during the cyclosporin era. 393 orthotopic liver transplantations accomplished in 313 consecutive patients at the Pittsburgh Transplantation Center].

During the cyclosporine era 1980-1984, 393 consecutive orthotopic liver transplantations (OLT) were performed in 313 patients at the University of Pittsburgh. This paper analyses the long-term results in this group of patients who have been followed-up for a minimum of three years. The results of OLT for different indications are discussed. The five-year survival rates after OLT for metabolic diseases, biliary atresia, primary biliary cirrhosis, posthepatic cirrhosis and primary hepatobiliary cancer are 75%, 68%, 60%, 58.9%, 53.2% and 23.8%, respectively. Recurrence of the primary disease after OLT is rare for benign diseases but rather frequent for malignant ones. The incidence of retransplantation for delayed rejection and for extrahepatic complications is discussed. The quality of life for most of the long-term survivors is good. Because of its good long-term results, OLT should become the therapy of choice in a lot of acute and chronic hepatopathies.

Cyclosporins↗
PubMed1997

Karyotype in acute myeloblastic leukemia: prognostic significance for bone marrow transplantation in first remission: a European Group for Blood and Marrow Transplantation study. Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

The presentation cytogenetic result was correlated with outcome for 999 patients with acute myeloblastic leukemia (AML) having bone marrow transplantation (BMT) in first complete remission (CR1). The karyotype at diagnosis was classified according to the modified Chicago classification. Allogeneic BMT (AlloBMT) was performed in 500 patients and autologous BMT (ABMT) in 499 patients. For both groups, an abnormal chromosome (abn) 5 and/or 7 or a hypodiploid karyotype had a poor outcome, whereas t(15;17), pseudodiploidy, hyperdiploidy and diploidy were associated with a standard prognosis. Abn (16) and t(8;21) were also of standard prognosis for ABMT, but favorable for AlloBMT. When comparing AlloBMT and ABMT in patients with favorable or standard cytogenetics, AlloBMT was of benefit for remission duration and leukemia-free survival (LFS). Patients with an unfavorable karyotype had a similar outcome, regardless of type of BMT. By multivariate analysis, cytogenetics at diagnosis had the strongest prognostic value for relapse, LFS, and survival in AlloBMT. In ABMT, cytogenetics influenced relapse and LFS. We concluded that the karyotype at diagnosis had important prognostic implication in AML grafted in CR1.

Adolescent↗
PubMed1997

Blood and marrow transplantation activity in Europe 1995. European Group for Blood and Marrow Transplantation (EBMT).

In 1995, a total of 12,101 blood or marrow transplants, performed in Europe by 343 teams from 31 countries, were reported to the European Group for Blood and Marrow Transplantation (EBMT). Of these, 3858 (32%) were allogeneic, 8243 (68%) autologous transplants. Of the autologous transplants 1384 (17%) were bone marrow derived, 6504 (79%) from peripheral blood stem cells and 355 (4%) combined bone marrow and peripheral blood stem cell transplants. Of the allogeneic transplants, 571 (15%) were peripheral blood stem cell transplants, the remainder, 3287 (85%) bone marrow transplants. Main indications were leukemias with 4408 transplants (36%), 2977 allogeneic (68%) and 1431 autologous (32%); lymphomas with 4671 transplants (39%), 272 allogeneic (6%) and 4399 autologous (94%); severe aplastic anemia with 237 transplants (2%), 237 allogeneic (100%) and 0 autologous (0%); solid tumors with 2399 transplants (20%), 17 allogeneic (1%) and 2382 autologous (99%); and congenital disorders with 294 transplants (2%), 294 allogeneic (100%) and 0 autologous (0%) and others with 92 transplants (1%), 61 allogeneic (66%) and 31 autologous (34%). There were major differences between participating countries. The absolute numbers of teams and transplants per country differ widely and range from 0.2 to 33.3 teams per 10 million inhabitants (median 5.8); 3.2 to 733.3 total transplants per 10 million (median 200); 0.7 to 210 allogeneic transplants per 10 million (median 65); 0.3 to 700 autologous transplants per 10 million (median 122); 0 to 47.7 unrelated transplants per 10 million inhabitants (median 8.7). There is also a difference in the relative number of transplants for the individual indications. The coefficient of variation for selected diseases was calculated for those 14 countries with a minimum of 100 transplants. A narrow coefficient of variation indicates consensus amongst grafting physicians. It is narrowest for chronic myeloid leukemia in allogeneic transplants (36.7%) and for Hodgkin's disease in autologous transplants (44.8%). These data reflect the present status of blood and marrow transplantation in Europe and provide a basis for patient counselling and health care planning.

Anemia, Aplastic↗
PubMed1994

The effect of transplant center volume on cardiac transplant outcome. A report of the United Network for Organ Sharing Scientific Registry.

OBJECTIVE: The number of cardiac transplant programs continues to increase despite no increase in the number of hearts available for transplantation. As a result, the majority of heart transplant centers perform extremely small numbers of transplant operations annually. To determine the effect of small transplantation volume on transplant outcome, the following study was performed. DESIGN: Using the Scientific Registry of the United Network for Organ Sharing, all cardiac transplant procedures from October 1987 through December 1991 were analyzed to determine whether center volumes affected cardiac transplant outcome. Patient survival rates for each center were determined, and the survival rates were modeled for the following patient variables: first transplantation or retransplantation, patient condition at the time of transplantation, patient underlying cardiac disease (congenital vs all others), and time. SETTING: All cardiac transplant centers in the United States were included in the analysis. PATIENTS: All patients undergoing cardiac transplantation in the United States from October 1987 through December 1991 were included in the analysis. MAIN OUTCOME MEASURE: The primary end point in this analysis was mortality. RESULTS: Throughout the entire study, of the 150 cardiac transplant centers, 35.3% of the centers were performing fewer than five cardiac transplantations per year, 53.3% were performing fewer than nine transplantations per year, and 61.3% were performing fewer than 12 transplantations per year, the minimum required for Medicare payment eligibility. Using the modeled survival rates, the risk of mortality decreased to a basal level in those centers performing between eight and 10 transplant operations per year. In centers performing fewer than nine transplantations, mortality increased sharply and exponentially. Dividing centers into those that performed nine or more transplantations per year (70 centers) and fewer than nine transplantations per year (80 centers), the increased risk of mortality at 1 month and 12 months was 40.3% and 33.1%, respectively, in centers performing fewer than nine cardiac transplantations per year (P < .001). Once the threshold of nine transplant procedures was met, those centers that were eligible for Medicare payment did not have significantly better survival than those centers not eligible for Medicare coverage. CONCLUSIONS: These data demonstrate that the risk of mortality at early and intermediate time points is substantially higher in low-volume cardiac transplant centers, which make up more than half of the centers performing cardiac transplantation in the United States.

Adolescent↗
PubMed1999

Blood and marrow transplantation activity in Europe 1997. European Group for Blood and Marrow Transplantation (EBMT).

Data from the annual survey on transplant activity 1997, collected from 457 transplant teams in 31 European countries by the European Group for Blood and Marrow Transplantation (EBMT) were used to describe current status and to assess relative and absolute changes in indication, donor type and stem cell source compared to 1991. A total of 16950 patients were reported to have a first blood or marrow transplant in 1997, a total of 18 923 procedures, including re- and double transplants were performed. Of the 16950 first transplants, 4751 (28%) were allogeneic, 12199 (72%) autologous transplants. Of the autologous transplants, 829 (7%) were bone marrow derived, 11370 (93%) from peripheral blood stem cells or combined bone marrow and peripheral blood stem cell transplants. Of the allogeneic transplants, 3311 (70%) were bone marrow, 1440 (30%) were peripheral blood stem cell transplants. In 1991, the respective figures were 2175 allogeneic (44%) and 2786 (56%) autologous transplants, more than 90% of the autologous, all allogeneic transplants bone marrow derived. Main indications in 1997 were leukemias with 5253 transplants (31%), 70% allogeneic; lymphomas with 6773 transplants (40%), 94% autologous; solid tumors with 4154 transplants (24%), 99% autologous; non-malignant disorders with 770 transplants (5 %), 85 % allogeneic. There was an absolute increase of 11971 transplants since 1991. An increase was observed in all disease categories. Marked differences were found, when the relative increase index (RII) for specific disease categories over time was analyzed. In allogeneic transplants, relatively more transplants were performed in 1997 for acute myeloid leukemia beyond 1st complete remission (RII 1.28), myelodysplastic syndromes (RII 1.58), chronic lymphocytic leukemia (RII 1.33) and non-Hodgkin's lymphoma (RII 1.58). For autologous transplant indications, a high relative increase index was observed in myelodysplastic syndromes (RII 3.77), in multiple myeloma (RII 2.12) and carcinoma of the breast (RII 6.37) with a relative decrease in leukemias (RII 0.39) and certain solid tumors such as glioma (RII 0.27) and neuroblastoma (RII 0.46). These data present the current status of blood and marrow transplantation in Europe. They show the change from bone marrow to blood as stem cell source and highlight shifts in indication. They provide a basis for patient counselling and health care planning.

Bone Marrow Transplantation↗
PubMed1999

Auxiliary versus orthotopic liver transplantation for acute liver failure. EURALT Study Group. European Auxiliary Liver Transplant Registry.

BACKGROUND/AIMS/METHODS: We report 1-year results after auxiliary liver transplantation for acute liver failure in a cohort of 47 patients transplanted in 12 European centers as compared with those of 384 consecutive patients undergoing orthotopic liver transplantation for acute liver failure in the Eurotransplant area. RESULTS: One-year patient survival resp. retransplant-free patient survival did not differ between orthotopic (61%, 232/384 resp. 52%, 200/384) and auxiliary liver transplantation (62%, 29/47 resp. 53%, 25/47). One-year patient survival resp. retransplant-free patient survival after auxiliary partial orthotopic liver transplantation was 71% (25/35) resp. 60% (21/35), not significantly different from orthotopic liver transplantation (61%, 232/384 resp. 52%, 200/384), while both transplantation techniques had better 1-year patient survival resp. retransplant-free patient survival than after heterotopic auxiliary liver transplantation (33%, 4/12) (p < 0.05). Primary nonfunction was more frequent after heterotopic auxiliary liver transplantation (3/12, 25%) than after orthotopic liver transplantation (21/384, 5.5%), while the incidence did not differ between orthotopic liver transplantation and auxiliary partial orthotopic liver transplantation (3/35, 8.5%). Portal vein thrombosis was more frequent after both heterotopic auxiliary liver transplantation (5/12, 42%) and auxiliary partial orthotopic liver transplantation (5/35, 14%) than after orthotopic liver transplantation (2/384, 0.5%) (p < 0.001). Of the patients, 65% (17/26) surviving auxiliary liver transplantation for 1 year without retransplantation by orthotopic liver transplantation were free of immunosuppression within 1 year, compared with none of the patients transplanted by orthotopic liver transplantation (p < 0.01). CONCLUSIONS: Auxiliary liver transplantation, especially auxiliary partial orthotopic liver transplantation, offers an advantage over orthotopic liver transplantation in acute liver failure in terms of a chance of a life free of immunosuppression, apparently without jeopardizing chances of survival. Reduction of the incidence of primary nonfunction and vascular complications should be a focus of research in auxiliary liver transplantation. These findings need to be confirmed in a prospective study.

Adolescent↗