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PubMed1995

Rat heart-aorta cluster transplantation: a novel model to study transplant rejection.

The purpose of this study was to develop a microsurgical cluster model of heart plus entire thoracic aorta transplantation and to compare it to the isolated model of heart transplantation as a tool to study transplant rejection. Thirty-six syngeneic (DA x DA and Lew x Lew) and allogeneic (DA x PVG and DA x Lew) cluster heart-aorta transplants were compared to 43 syngeneic and allogeneic isolated heart grafts. Graft survival, recipient survival and histological data on myocardial and aortic tissues were assessed. There was no statistically significant difference in graft survival between the two models studied (P > 0.05). In the cluster transplants, the aortic component was spared the severity of acute rejection noted for the myocardial counterpart. In conclusion, the results demonstrated that the cluster model was technically feasible and highly reproducible. Additionally, it was possible to apply this model to the study of experimental allograft rejection using novel immunosuppressants. The success of the cluster model in strongly mismatched transplant strain combinations underscores its potential for application in slower rejection combinations, making it particularly suited for chronic rejection studies. The inherent capacity for sampling a broader range of vessel sizes in one animal makes the cluster model more suitable than the isolated models of aorta or heart for application to experimental protocols.

Animals↗
PubMed1991

Echocardiographic findings in kidney transplanted type 1 (insulin-dependent) diabetic patients with and without a pancreas transplant.

Echocardiography with Doppler recordings was carried out in 14 Type 1 (insulin-dependent) diabetic recipients of pancreas and kidney transplants and in 14 Type 1 diabetic kidney transplanted control patients, matched for age, sex, duration of diabetes, extent of other late complications, time since transplantation, dose of prednisolone, and renal function. HbA1c was 5.5 +/- 0.6 vs 8.7 +/- 1.4% (pancreas transplanted vs kidney only). Both groups had a slight increase in interventricular septum thickness. Left ventricular mass was equal. The ejection fraction as a measure of systolic function was normal and equal, 0.71 +/- 0.05 vs 0.69 +/- 0.07. Diastolic function was also equal in two out of three parameters, isovolumic relaxation time and deceleration time. The A/E ratio, however, tended to be lower in the pancreas transplanted group, 0.94 +/- 0.20 vs 1.06 +/- 0.18 (p = 0.04). This indicates more frequent occurrence of impaired diastolic filling in the recipients of kidney only. Follow-up will show whether diastolic dysfunction increases and may be related to the increased cardiovascular mortality in kidney transplanted Type 1 diabetic patients.

Adult↗
PubMed2000

Transplant activities in Germany in 1998--a survey facilitated by the National Registry for Hemopoietic Stem Cell Transplantation.

To improve the infrastructure of hemopoietic stem-cell transplantations in our country, the German Registry for Hemopoietic Stem-Cell Transplantations (DRST) was established in 1998. The present paper summarizes the current status of the DRST and gives a survey of transplant activities in Germany in 1998 in terms of transplant units, transplant types, transplant frequencies and underlying diseases.

Blood Cells↗
PubMed1997

Renal transplantation, chronic dialysis, and chronic renal insufficiency in children and adolescents. The 1995 Annual Report of the North American Pediatric Renal Transplant Cooperative Study.

The 1995 Annual Report of the North American Pediatric Renal Transplant Cooperative Study summarizes data voluntarily collected from 123 centers on 5,197 children and adolescents grouped into three cohorts: (1) patients who received renal transplants on or after 1 January 1987 (n = 3,066), (2) patients who were maintained on peritoneal dialysis (PD) or hemodialysis (HD) on or after 1 January 1992 (n = 1,488), and (3) patients treated for chronic renal insufficiency (CRI) on or after 1 January 1994 (n = 643). The transplant and dialysis information update previous registry data whereas the CRI information reflects 1st-year registry data. Three-year graft survival rates were 83% and 66% for living donor grafts and cadaver donor (CD) grafts, respectively. Triple drug maintenance therapy with prednisone, cyclosporine, and azathioprine was used by > 70% of all transplant recipients through 5 years of follow-up. The 2-year CD survival has steadily improved from 65% in 1987 to 82% in 1992. Fifty malignancies have been reported, the majority of which are lymphoproliferative disorders. The 2-year patient survival posttransplantation is 95%. Mortality rates for the youngest patients have drastically improved over the past 2 years. Approximately two-thirds of patients in the dialysis cohort are maintained on PD; automated PD remains the preferred modality. Overall, the peritonitis rate is one infection every 13.3 patient months, the frequency of infection being greatest in the youngest patients. Whereas the primary reason for dialysis modality termination is transplantation approximately 40% of the entire dialysis cohort (PD at HD) were not considered active transplant candidate Baseline CRI data revealed the most common primary diagnoses to be obstructive uropathy (24%) and aplastic/hypoplastic/dysplastic kidneys (19%). The standardized height deficit in the CRI cohort was greatest in the younger patients and those with the most impaired renal function.

Adolescent↗
PubMed2005

Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation.

The syndrome of microangiopathic hemolysis associated with renal failure, neurologic impairment, or both is a recognized complication of hematopoietic stem cell transplantation. This entity is often called hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP), yet it is clear that the pathophysiology of transplant-associated HUS/TTP is different from that of classic HUS or TTP. Furthermore, the incidence of this syndrome varies from 0.5% to 76% in different transplant series, primarily because of the lack of a uniform definition. The toxicity committee of the Blood and Marrow Transplant Clinical Trials Network has reviewed the current literature on transplant-related HUS/TTP and recommends that it be henceforth renamed posttransplantation thrombotic microangiopathy (TMA). An operational definition for TMA based on the presence of microangiopathic hemolysis and renal and/or neurologic dysfunction is proposed. The primary intervention after diagnosis of TMA should be withdrawal of calcineurin inhibitors. Plasma exchange, although frequently used in this condition, has not been proven to be effective. In the absence of definitive trials, plasma exchange cannot be considered a standard of care for TMA. It is hoped that these positions will improve the identification and reporting of this devastating complication after hematopoietic stem cell transplantation and facilitate future clinical studies for its prevention and treatment.

Clinical Trials as Topic↗
PubMed2006

Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation.

This is an update of a randomized study on antithymocyte globulin (ATG; Thymoglobulin) before transplantation in patients undergoing unmanipulated marrow transplantation from unrelated donors. The median follow-up for surviving patients is 5.7 years. At last follow-up, chronic graft-versus-host disease (GVHD) was scored in 60% of non-ATG and in 37% of ATG patients (P=.05), and extensive chronic GVHD was present in 41% and 15%, respectively (P=.01). Chronic lung dysfunction was diagnosed in 51% versus 19% of patients (P=.005). Forced vital capacity decreased significantly with time in non-ATG patients (P=.005), but not in patients who received ATG (P=.30). The proportion of patients with Karnofsky scores of >or=90% at 4 years was 57% versus 89% in non-ATG versus ATG patients (P=.03). The actuarial 6-year survival for all patients randomized was 31% versus 44% (non-ATG versus ATG; P=.80). The cumulative incidence of transplant-related mortality was 51% versus 41% (P=.70) and of relapse was 32% versus 40% (P=.90). For patients who survived 1 year, transplant-related mortality was 25% versus 3% (P=.03), and actuarial survival was 58% versus 85% (P=.09). In conclusion, the addition of ATG to cyclosporine/methotrexate provides significant protection against extensive chronic GVHD and chronic lung dysfunction, reduces late transplant mortality, and improves quality of life in patients undergoing unrelated donor transplantation.

Adolescent↗
PubMed2006

The effect of gender combinations on outcome in human lung transplantation: the International Society of Heart and Lung Transplantation Registry experience.

BACKGROUND: In the current practice of lung transplantation, donor and recipient genders are neither directly considered nor matched. METHODS: We analyzed the potential effect of gender combinations on survival in 9,651 lung transplant recipients in the International Society of Heart and Lung Transplantation Registry (ISHLT) Registry. We compared the risk of overall and 90-day mortality by using statistical models that accounted for confounding variables. RESULTS: A Kaplan-Meier survival analysis revealed a significant difference of survival among gender combinations (log rank, p = 0.0009). The unadjusted odds ratio (OR) of 90-day mortality was significantly higher in female (F) donors to male (M) recipients (OR, 1.58; 95% confidence interval (CI), 1.22-2.04; p < 0.001) and lower in F to F (OR, 0.742; 95% CI, 0.61-0.90; p = 0.004) compared with the reference category of M to M. After adjusting for size mismatch and diagnosis in the multivariate logistic regression model, the OR of F to M was still statistically significant (F to M OR, 1.52l; 95% CI, 1.04-2.20; p = 0.028; F to F OR, 0.67; 95% CI, 0.53-0.91; p = 0.008) for 90-day mortality. A Cox proportional hazards analysis for overall survival also showed a significantly higher hazard ratio of 1.12 in F to M (95% CI, 1.01-1.23) and a lower hazard ratio of 0.92 in F to F (95% CI, 0.87-0.98). CONCLUSION: ISHLT Lung Transplant Registry data demonstrated a significant risk for F to M. Interestingly, F to F appears to be potentially beneficial in lung transplantation. Gender combinations do appear to significantly impact outcome after lung transplantation.

Adult↗
PubMed2004

Outcomes in cardiac transplant recipients using allografts from older donors versus mortality on the transplant waiting list; Implications for donor selection criteria.

OBJECTIVES: This study investigates the outcomes of cardiac transplantation using older donors. BACKGROUND: Despite high mortality rates on waiting lists, transplanting hearts from older donors remains a relative contraindication. METHODS: We retrospectively reviewed data on 479 adult heart transplant recipients, 352 status I patients, and 534 status II patients enrolled on a waiting list between 1992 and 1999. The Cox proportional hazards model was used for statistical analysis. RESULTS: Of all donors, 20% were 40 to 50 years old and 8% were > or =50 years old. The risk of six-month mortality on the waiting list for patients who were not transplanted (status I: relative risk [RR] 8.5; status II: RR 3.7) significantly outweighed the risk of transplanting patients with a heart from donors >40 years old (status I: RR 1.6; status II: RR 2.1). Recipients of cardiac allografts from donors <40 years old had a one-month mortality rate of 5%, in contrast to 13% and 22% in those receiving allografts from donors 40 to 50 years old and > or =50 years old, respectively. Donor age did not influence long-term survival or frequency of rejections; however, it did correlate with the early presence of transplant-related coronary artery disease (TCAD). By the first annual angiogram, only 17% of recipients with donors <20 years old developed TCAD, in contrast to 26% to 30% and 34% of recipients who received allografts from donors age 20 to 40 years and >40 years, respectively. CONCLUSIONS: Despite a strong association between older donor age and increased post-operative mortality and TCAD, it is more beneficial in terms of patient survival to receive an allograft from a donor >40 years old than to remain on the waiting list.

Adolescent↗
PubMed2004

Domino liver transplant: influence on the number of donors and transplant coordination.

The shortage of organs forces coordinators to seek new forms of generating organs for transplantation of the increasing numbers of patients on waiting lists. A recent technique called sequential transplant or domino liver transplant (DLT) allows the transplantation of a patient with chronic liver disease by implantation of a full-size liver derived from a patient with familial amyloidosis polyneuropathy (FAP) who receives a cadaveric graft. Therefore, it is possible to transplant two patients with only one cadaveric liver. The present report illustrates the use of this technique for the first time in our country, thereby increasing the number of hepatic transplants by 25%.

Humans↗
PubMed2005

Cardiovascular benefits of simultaneous pancreas-kidney transplant versus kidney alone transplant in diabetic patients.

UNLABELLED: The aim of our study was to demonstrate the cardiovascular benefits of simultaneous pancreas-kidney transplantation when compared to kidney-alone transplants in diabetic recipients. PATIENTS AND METHODS: A total of 386 renal transplants were performed from 1985 to 2004, including 262 (68%) in diabetic recipients and 124 (32%) in nondiabetics. Among the former group, 200 kidneys were transplanted simultaneously to the pancreatic graft (KP group) and 62 were kidney-alone transplants (KA group). The mean time on dialysis was 31 +/- 20 months (range 0-126 months). The duration of diabetes was 24 +/- 7 years (range 5-51 years). Ninety-nine percent of the patients were on renal replacement therapy (79% on hemodialysis and 20% on peritoneal dialysis). RESULTS: Among 262 patients, 28 (11%) died due to a cardiovascular event, which was higher among KA patients compared with the KP group (P = .004). Overall patient survival was significantly higher in the KP group when compared with the KA group (log-rank: P = .0004). Patient survivals were 80% and 70% versus 70% and 40% at 5 and 10 years in the KP and KA groups, respectively. Kidney graft survivals were 81% and 60% versus 63% and 26% at 5 and 10 years in the KP and KA groups, respectively. Pancreas graft survival was 70% and 50% at 5 and 10 years, respectively. CONCLUSIONS: This clinical evaluation, even if retrospective, confirmed that simultaneous pancreas-kidney transplantation has a protective effect against cardiovascular mortality in diabetic recipients affected by end-stage renal disease.

Cardiovascular Physiological Phenomena↗
PubMed1985

Further cardiac transplant procedures in patients with heterotopic heart transplants.

Seven patients with heterotopic heart transplants have undergone further heart transplant procedures. In 5, the first heterotopically placed donor heart was excised and replaced with the second donor heart. In 2, the first heterotopic donor heart was left in situ and the patient's own heart (then nonfunctioning) was excised and replaced by the second donor heart; thus, these patients underwent orthotopic transplantation and were left with two donor hearts. The decision to perform retransplantation in a patient undergoing irreversible acute rejection is usually straightforward, but the timing of a further transplant procedure in a patient with advanced graft arteriosclerosis may present a difficult problem. Two of the 7 patients in this series died of infectious complications within the first 3 months after retransplantation. A third patient acutely rejected the second donor heart within 5 days, but survived an additional 17 months with the support of his own cardiomyopathic heart. Four patients remain alive and well between 5 and 36 months following the second transplant and between 17 and 54 months following the first transplant procedure.

Acute Disease↗
PubMed1998

Autologous transplantation of urothelium into demucosalized gastrointestinal segments: evidence for epithelialization and differentiation of in vitro expanded and transplanted urothelial cells.

PURPOSE: Our study established a technique for in vitro expansion and subsequent transplantation of autologous urothelial cells into vascularized seromuscular segments from stomach and colon in sheep. The proof of proliferation and differentiation of the transplanted urothelium in the absence of resident urothelium is considered to be a prerequisite for use of this technique in bladder augmentation. MATERIALS AND METHODS: Autologous sheep urothelial cells were expanded in vitro and grown on collagen membranes for sheet grafting. Using a vital stain, viability and confluency status of the urothelial graft were determined before transplantation into demucosalized segments isolated from the sheep stomach and colon gastrointestinal pouches. The gastrointestinal segments were sewn up and remained in the abdomen as small pouches stiched to the abdominal wall. Take and differentiation of transplanted cells within the pouch were assessed two and three weeks later using histological and immunohistological means. RESULTS: Urothelial cells grew well on collagen membranes. A confluency status > 40% and co-culturing with 3T3 feeder cells favored successful transplantation. Two weeks after transplantation a multilayered urothelial-like epithelium was found to line the lumen of the pouch. The epithelium was characterized by a distinct urothelium-typical distribution of basal and luminal keratins and the expression of the umbrella cell-specific marker uroplakin III. Moreover, the epithelium had an underlying basal lamina which focally contained collagen type IV. CONCLUSIONS: The data indicate that in vitro expanded urothelial cells are capable of epithelializing demucosalized gastrointestinal segments forming a genuine, differentiated "neo" urothelium.

Animals↗
PubMed1980

Post-transplantation pyelonephritis: factors producing low patient and transplant morbidity.

A retrospective study of 1,100 consecutive renal transplantations done on 959 patients revealed postoperative pyelonephritis in 15 patients, 14 of whom were women. Sixteen of the 20 episodes of pyelonephritis were caused by Escherichia coli and only 4 episodes occurred within the first year after transplantation, thus revealing the crucial differentiation from a rejection episode. When the etiology of the original renal failure was pyelonephritis the incidence of pyelonephritis in the transplanted kidneys was high. This high incidence also was true for cases associated with post-transplantation urological complications. When the etiology of renal failure was diabetes or polycystic renal disease, or when urologic abnormalities pre-existed the incidence of pyelonephritis was low. No transplant or patient loss was caused by post-transplantation pyelonephritis, probably because of prompt, correct diagnosis and a low urological complication rate.

Adult↗
PubMed1995

Endorectal pull-through of transplanted colon as part of intestinal transplantation.

BACKGROUND: Two children with life-threatening disorders underwent intestinal transplantation; one multivisceral transplantation excluding the liver, and the second transplantation of the liver, small bowel, and colon. METHODS: Involvement of the native rectum necessitated resection and replacement with the transplanted allograft. To prevent a permanent colostomy, a pull-through of the allograft colon was performed. RESULTS: Both patients had a stormy early postoperative course, mainly because of the complexities of intestinal transplantation, but with eventual recovery, including improvement of rectal function. CONCLUSIONS: These are the first two known cases in which a transplanted large intestine was used for a pull-through procedure.

Colon↗
PubMed1976

Parent-to-child and child-to-parent kidney transplants. Experience with 101 transplants at one centre.

101 first transplants were done in patients with end-stage renal disease using kidneys from parents or offspring. All patients were followed up for at least two years, and the absolute two-year patient-survival rate was 88% and the two-year functional-kidney rate was 79%. Actuarial statistics at four years were 82% for survival and 67% for function in the parent-to-child group. In the child-to-parent group absolute patient survival was 83% and transplant function was 79% at two years; these results were unchanged at four years. Thus, transplants from parents to children or from children to parents are much the same despite differences in age. There is some advantage in parent-to-child transplants from being female but no advantage in being diabetic, receiving higher or lower doses of antilymphocyte globulin, or sharing more than two HLA antigens with the donor. Mismatched sibling transplants survived approximately as well as did grafts from parents to children and children to parents. These results, taken in concert with the poor results of cadaver transplantation, the relative safety of donation, the high personal motivation to donate in these groups, and the personal satisfaction derived by the donor, strongly support the policy of informing potential recipients of the benefits of parental or offspring kidney donation.

Adolescent↗
PubMed2000

The effect of prelung transplant clinical status on post-transplant survival of children with cystic fibrosis.

The aim of this study was to determine whether transplanting paediatric cystic fibrosis (CF) patients later in the course of their disease was detrimental to their post-transplant survival. Data was collected from 51 children with CF undergoing lung or heart-lung transplantation May 1988-March 1999. The following risk factors were tested by Cox proportional hazards modelling: age at transplant; sex; donor/recipient sex mismatch; donor/recipient cytomegalovirus (CMV) mismatch; cold and warm graft ischaemic times; and donor age. Pretransplant forced expiratory volume in one second (FEV1), minimum oxygen saturation obtained during 12 min walk (Sa,O2min), and a survival probability score (SP) calculated from FEV1, age adjusted resting heart rate, age, sex, blood haemoglobin (Hb), and serum albumin were then added to the model. None of the risk factors were significantly correlated with death during the study period. No evidence that clinical status prior to transplant has any effect upon the post-transplant survival of children with cystic fibrosis was found.

Adolescent↗
PubMed1997

High-dose chemotherapy, autologous bone marrow or stem cell transplantation and post-transplant consolidation chemotherapy in patients with advanced breast cancer.

This study was designed to determine the complete response (CR) rate, event-free survival (EFS) and overall survival (OS) in patients with metastatic breast cancer treated with an adriamycin-based induction regimen, high-dose chemotherapy consisting of cyclophosphamide and thiotepa with autologous bone marrow or stem cell reinfusion, followed by post-transplant 5-fluorouracil and cisplatin. Forty-eight consecutive patients were enrolled and 35 received two to four cycles of a cytoreductive chemotherapy regimen followed by high-dose chemotherapy which included cyclophosphamide and thiotepa. Thirty-three patients with non-progressive disease received at least one cycle of post-transplant 5-fluorouracil and cisplatin. Fifty percent of patients with evaluable disease responded to induction chemotherapy. Three of the 34 patients (9%) evaluable for response to high-dose chemotherapy achieved CR, eight (24%) achieved partial response (PR), 12 (35%) had stable disease (SD) and 11 (32%) had progressive disease (PD). The median time to neutrophil recovery was 11.5 days (range, 8 to 40 days) post- reinfusion. The median time to platelet independence was 14.5 days (range, 8 to 44 days). The median follow-up is 24.5 months (range, 1 to 96 months). The actuarial probability of EFS for all patients is 17% at 4 years. The EFS for patients receiving all four cycles of post-transplant chemotherapy is 27% at 4 years, compared to 36% at 1 year for patients not receiving any post-transplant chemotherapy. Ten of the 48 patients (21%) are alive, and seven of these (15%) have no evidence of disease. High-dose chemotherapy with autologous bone marrow or peripheral blood-derived stem cell transplantation followed by post-transplant consolidation chemotherapy in patients with metastatic breast cancer results in a proportion of patients without evidence of disease at 4 years.

Adult↗
PubMed1998

Successful salvage using mismatched umbilical cord blood transplant in an adult with recurrent acute myelogenous leukemia failing autologous peripheral blood progenitor cell transplant: a case history and review.

We report a 26-year-old female with AML, FAB classification M5 who was initially treated with induction therapy consisting of idarubicin and cytarabine followed by high-dose cytarabine and autologous peripheral blood progenitor cell (PBPC) transplant for consolidation. The patient remained in remission for 1 month post-PBPC transplant, when relapse was noted. Reinduction therapy with idarubicin, cytarabine and etoposide was unsuccessful, and the patient underwent an unrelated, two-antigen mismatched umbilical cord blood (UCB) transplant for salvage after melphalan plus total body irradiation. Complications post transplant included veno-occlusive disease, delayed engraftment, and acute grade III graft-versus-host disease (GVHD). The patient remains in remission 1 year post transplant. This study demonstrates the salvage capability of UCB transplantation for refractory leukemia and its potential use in adult patients.

Adult↗