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PubMed2001

Renal transplantation following previous heart, liver, and lung transplantation: an 8-year single-center experience.

BACKGROUND: Long-term follow-up of heart, liver, and lung transplantation has led to an increased recognition of secondary end-stage renal failure (ESRF) in transplant recipients. This study examines our center's experience with renal transplantation following previous solid organ transplantation. METHODS: From January 1, 1992, to September 30, 1999, our center performed 18 renal transplants in previous solid organ recipients. During the same period, 815 total renal transplants were performed. One- and 3-year graft and patient survival, recipient demographics, donor type, and reason for transplantation were compared between these groups. RESULTS: Of the 18 recipients, 7 had prior heart transplants, 4 had prior liver transplants, and 7 had prior lung transplants. Cyclosporine toxicity contributed to renal failure in 17 (94.4%) of the patients-either as a sole factor (11 patients) or in combination with hypertension, renal artery stenosis, or tacrolimus toxicity (6 patients). Kaplan-Meier 1- and 3-year patient survival was 82.9% and 73.7%, compared with 95.5% and 90.7% in all renal transplant recipients. No surviving patient has suffered renal allograft loss. Mean current creatinine level is 1.4 mg/dL. CONCLUSIONS: Renal transplantation is an excellent therapy for ESRF following prior solid organ transplantation. One and 3-year patient and graft survival demonstrate the utility of renal transplantation in this patient population.

Follow-Up Studies↗
PubMed1995

Indications and donor source of hematopoietic stem cell transplants in Europe 1993: report from the European Group for Blood and Marrow Transplantation (EBMT).

This report details the evolution of bone marrow transplantation in Europe over a 20-year period. In 1973, 8 teams undertook a total of 16 allogeneic bone marrow transplants; in 1983, 97 teams performed 1353 transplants. In 1993, the numbers had risen to 260 teams and 7737 transplants. Donor source in 3092 cases was an allogeneic donor (2464 HLA-identical sibling transplants, 147 non-identical family donor transplants, 25 twin donor transplants and 456 unrelated donor transplants). For 4645 patients the transplant was autologous (2450 autologous bone marrow transplants, 1830 autologous peripheral blood stem cell transplants and 365 combined autologous peripheral blood and bone marrow transplants). Indications for transplants in 1993 were leukemias in 3419 patients (44%; 2332 allogeneic, 1087 autologous), lymphoproliferative disorders in 2666 patients (34%; 197 allogeneic, 2469 autologous), solid tumors in 1077 patients (14%; 9 allogeneic, 1068 autologous), aplastic anemia in 251 patients (3%; 250 allogeneic, 1 autologous), inborn errors in 244 patients (3%; 242 allogeneic, 2 autologous) and miscellaneous disorders in 80 patients (1%; 62 allogeneic, 18 autologous). These data illustrate the increase of hematopoietic stem cell transplants as a therapeutic modality over the last 20 years in Europe.

Bone Marrow Transplantation↗
PubMed1995

Worldwide thoracic organ transplantation: a report from the UNOS/ISHLT International Registry for Thoracic Organ Transplantation.

The number of heart transplant operations performed in the United States has grown modestly as indicated by an 11% increase from 1990 (n=2,108) to 1994 (n=2,340). From 1987 (n=18) to 1993 (n=666), lung transplant procedures have increased by 3600%. This trend continued with 722 procedures performed in 1994 and 760 (22% increase from 1993) currently reported for 1995. Non-US heart transplants have also leveled during recent years. The number of new heart transplant programs in the United States has not increased during the last 2 years with no change from 1993-1994 and a decrease of 2 heart programs from 1994-1995. From 1990 (n=37) to 1995 (n=71), the number of centers performing lung transplantation increased by 92%. No significant changes were noted in the number non-US heart or lung programs from 1993-1994. The most frequently reported US indications for thoracic transplantation were coronary artery disease (43.5%) for heart, cystic fibrosis (37.9%) for double lung, emphysema/COPD (44.1 %) for single lung and congenital lung disease (40%) for heart-lung. The most frequently reported non-US diagnoses for thoracic transplantation included cardiomyopathy (48.8%) for heart, cystic fibrosis (39.4%) for double lung, idiopathic pulmonary fibrosis (31.4%) for single lung and primary pulmonary hypertension (24.3%) for heart-lung. US heart transplant recipients were predominantly male (77.9%), over 50 years of age (54.3%) and white (83.3%); while US lung transplant recipients were predominantly female (53.2%), between 35- 64 years of age (73.2%) and white (90.7%). No significant variance from the US recipient demographic profile was noted for non-US recipients in this analysis. Differences were noted in the percent distribution of non-US and US donor causes of death. The top US causes of donor death were motor vehicle accidents (31.7%), cerebrovascular/strokes (24.0%), gunshot/stab wounds (23.2%) and non-motor vehicle head traumas (11.8%). The leading causes of donor death for non-US cases included cerebrovascular/strokes (55.7%), non-motor vehicle head traumas (28.7%), motor vehicle accidents (7.7%) and central nervous system tumors (3.0%). Gunshot/stab wounds accounted for only 0.9% of donor deaths. A leveling of US heart transplant one-year survival during recent years was indicated by a 1.5% increase from 1988-1994. Improvement in one-year US lung transplant survival was indicated by a rise from 35.3% in 1987 to 74.1 % in 1994. Non-US one-year survival rates were 77.5% for heart and 67.5% for lung in 1994. The long-term thoracic patient survival rates in the United States were: 36.9% at 11 years for heart, 41 % at 5 years for lung and 24.7% at 10 years for heart-lung recipients. Long-term survival rates for non-US cases were 37.1 % at 11 years for heart, 39.7% at 5 years for lung and 16.8% at 10 years for heart-lung. The most important risk factor for US heart recipients at one month, one year, 2 years and 3 years posttransplant was receipt of a previous heart transplant. Other substantial risk factors included congenital diagnosis, donor age greater than 50 years and recipient on a ventilator at the time of transplant. The most important risk factor for mortality in US lung recipients was the transplant number (primary or repeat). Diagnosis and ventilator use were also highly influential risk factors for mortality.

Adolescent↗
PubMed2006

Definitions of primary graft dysfunction after lung transplantation: differences between bilateral and single lung transplantation.

OBJECTIVE: The primary graft dysfunction definition has been applied to both bilateral lung transplantation and single lung transplantation. However, the differences between bilateral and single lung transplantation in terms of primary graft dysfunction remain unknown. This study aims to investigate the features and utility of the new primary graft dysfunction grading system by comparing early outcomes from bilateral and single lung transplantation. METHODS: The primary graft dysfunction grade of 228 consecutive lung transplants (149 bilateral and 79 single lung transplants) at multiple postoperative time points was analyzed. Subgroup analysis with chronic obstructive pulmonary disease was performed to further validate the difference between bilateral lung transplantation and single lung transplantation. RESULTS: The percentage of grade 3 primary graft dysfunction in bilateral and single lung transplants was 32% and 37% at 0 hours (T0), 9% and 33% at 12 hours (T12), 7% and 26% at 24 hours (T24), and 9% and 18% at 72 hours (T72), respectively. The prevalence of the grade 3 primary graft dysfunction (T24) was significantly different between those undergoing bilateral lung transplantation and those undergoing single lung transplantation (P = .02). The primary graft dysfunction grade (T0) significantly correlated with the duration of intubation in both bilateral (r = 0.35, P < .0001) and single (r = 0.42, P = .001) lung transplantation and length of intensive care unit stay in both bilateral (r = 0.31, P = .0002) and single (r = 0.33, P = .006) lung transplantation. These differences were validated by the subgroup analysis. CONCLUSIONS: The prevalence of primary graft dysfunction grade is different between bilateral and single lung transplantation and varies with time. Although the primary graft dysfunction grade correlated with the early posttransplantation outcomes, for the purposes of description and further studies, primary graft dysfunction in bilateral and single lung transplantation should be considered separately.

Adult↗
PubMed2001

Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience.

BACKGROUND: Increased referral for lung transplantation, persistent shortage of donor lungs, and moderate transplant outcome call not only for adequate listing criteria, but also for an optimal allocation scheme. We used global cohort survival after listing and survival benefit from transplantation to study the effect of a lung allocation scheme, primarily driven by waiting time, on the different types of end-stage lung disease. METHODS: We followed all adult patients consecutively listed for first, lung-only transplantation between 1990 and 1996 (n = 1,208) for at least 2 years, with an additional 2-year follow-up after transplantation (n = 744). We used the competing risk method, the Kaplan-Meier method, and a time-dependent non-proportional hazards model to analyze waiting-list outcome and global mortality after listing, post-transplant survival, and transplant effect, respectively. Each analysis was stratified for type of end-stage lung disease. RESULTS: At 2 years, 57% of the total cohort had received lung transplants, whereas 25% had died on the waiting list. The 2-year survival post-transplant was 55%. The global mortality of the cohort, since listing, amounted to 46% at 2 years. Compared with continued waiting, patients experienced benefit from transplantation by Day 100, which lasted until the end of the 2-year analysis period. We noticed the highest global mortality rates for patients with pulmonary fibrosis and pulmonary hypertension (54% and 52%); emphysema patients had the lowest (38%). Patients with pulmonary fibrosis and cystic fibrosis had much earlier benefit from transplantation, 55 and 90 days, respectively. Transplantation also benefited emphysema patients by Day 260. CONCLUSIONS: Lung transplantation conferred transplant benefit in a Western European cohort of adults, in particular for patients with pulmonary fibrosis and cystic fibrosis, but also for patients with emphysema. The global survival rate, reflecting the real life expectancy for a newly listed transplant candidate, is poor for patients with pulmonary fibrosis and pulmonary hypertension. Allocation algorithms that lessen the impact of waiting time and take into account the type of end-stage lung disease should be developed.

Adolescent↗
PubMed1999

Peripheral vascular disease and renal transplant artery stenosis: a reappraisal of transplant renovascular disease.

BACKGROUND: Renal transplant artery stenosis (RTAS) continues to be a problematic, but potentially correctable, cause of post-transplant hypertension and graft dysfunction. Older transplant recipients, prone to peripheral vascular disease (PVD), may have pseudoRTAS with PVD involving their iliac system. METHODS: We retrospectively analyzed 819 patients who underwent kidney transplantation between 1993 and 1997 to determine the contribution of pseudoRTAS to renal transplant renovascular disease. Univariate analyses were performed for donor and recipient variables, including age, weight, gender, race, renal disease, cholesterol and creatinine values, human leukocyte antigen (HLA) matching, cytomegalovirus (CMV) infection, and immunosuppressive medications. Significant variables were then analyzed by a Cox proportional hazards model. RESULTS: Ninety-two patients (11.2%) underwent renal transplant arteriogram (Agram) or magnetic resonance angiography (MRA) for suspected RTAS. RTAS or pseudoRTAS, defined as one or more hemodynamically significant lesions in the transplant artery or iliac system, was evident in 44 patients (5.4%). Variables significantly associated with RTAS by univariate analysis were weight at the time of transplant (p = 0.0258), male gender (p = 0.034), discharge serum creatinine > 2 mg/dL (p = 0.0041), and donor age (p = 0.0062). Variables significantly associated with pseudoRTAS by univariate analysis were weight at the time of transplant (p = 0.0285), recipient age (p = 0.0049), insulin-dependent diabetes mellitus (IDDM; p = 0.0042), panel reactive antibody (PRA) at transplant (p = 0.018), and body mass index (p = 0.04). Weight at transplant and donor age remained significantly associated with an increased risk for RTAS in a multivariate stepwise Cox proportional hazards model. IDDM, transplant PRA, weight at transplant, and donor age were significantly associated with an increased risk for pseudoRTAS in a multivariate stepwise Cox proportional hazards model. Importantly, both RTAS and pseudoRTAS were associated with poorer graft survival (p < 0.007 for each). CONCLUSIONS: Renal transplant renovascular disease encompasses pre-existing PVD acting as pseudoRTAS, as well as classical RTAS. Efforts to identify and correct renal transplant renovascular disease of either nature are important, given its negative impact on graft survival.

Adult↗
PubMed2003

The first report from the patient outcomes registry for transplant effects on life (PORTEL): differences in side-effects and quality of life by organ type, time since transplant and immunosuppressive regimens.

BACKGROUND: Post-transplant patient quality of life (QOL) is affected by a number of different factors. A nationwide patient registry has been established to evaluate QOL and determine the effects of transplant and immunosuppressive regimens on patient outcomes. METHODS: Patients were contacted directly at national meetings, through transplant centers, and patient support groups and invited to participate in the registry. All transplant patients aged 16 and over were eligible to enroll. Patients completed a 100-item self-administered questionnaire consisting of questions about patient demographics, organ functioning, and other post-transplant outcomes. General QOL was measured by the Short form - 12 (SF-12). The Memphis Survey, an instrument developed and psychometrically validated at the University of Tennessee, was administered to patients to evaluate side-effects associated with immunosuppression. Data were analyzed from the first 722 patients who entered the registry. Side-effect profile and QOL outcomes were evaluated by organ type, time since transplant and immunosuppressive regimen. Multiple regression analyses were conducted to determine predictors of post-transplant QOL. RESULTS: When outcomes were analyzed by organ type, there were no differences in SF-12 or total weighted Memphis scores. Analysis by time since transplant demonstrated that side-effects in the mobility domain increased with patient age and time since transplant. Analysis by immunosuppressive regimen focused on cyclosporine and tacrolimus-based regimens congruent with similar classifications reported in previous studies (Pirsch JD et al. Transplantation 1997: 63: 977, Shield CF III et al. Transplantation 1997: 64: 1738). When analyzed by regimen, there were no differences between the groups in terms of patients reporting good to excellent organ function, treatment for rejection, infection, and over-immunosuppression. Statistically significant differences were observed when side-effect profile was analyzed by immunosuppressive regimen. Patients on cyclosporine-based regimens reported greater overall side-effect severity and more problems with mobility and life roles. Cyclosporine patients also reported more problems in the miscellaneous subscale, including high blood pressure, enlarged gums and hair growth, but less trouble with trembling hands. Multiple stepwise regression models identified several side-effect subscales as having profound effects on mental and physical QOL. CONCLUSION: Transplant recipients report good to excellent levels of QOL, however, side-effects associated with immunosuppressive regimens impair post-transplant QOL. Problems in certain domains, such as mobility, are found to increase with time since transplant. Tacrolimus-based regimens are associated with fewer and less severe side-effects than cyclosporine-based regimens in key domains that affect post-transplant QOL.

Activities of Daily Living↗
PubMed2005

[Cost comparison of cadaveric liver transplantation with living-donor transplantation].

OBJECTIVE: To compare the cost of cadaveric liver transplantation with adult-adult right hepatic lobe living-donor transplantation. METHOD: Total cost of 25 cadaveric liver transplantations and 22 adult-adult right hepatic lobe living-donor transplantations was considered from the day of hospital admission until the day of discharge. Professional fees and expenses due to post-transplant complications and donor follow-up were not included. RESULTS: There was no difference in hospital stay between recipients of cadaveric transplantation (13.2+/- 4.1 days) and those of living-donor transplantation (15.4+/- 4.5 days). Costs of living-donor organ acquisition (USD 4,975.08+/- 565.34) were higher than those of cadaveric organ donation (USD 3,081.73+/- 305.57) (p<0.001). Implantation costs were similar for cadaveric and living-donor transplantation. Operating room and material costs were higher for living-donor transplantation and medications, exams and blood components costs were higher for cadaveric transplantation. The most expensive component of both cadaveric and living-donor liver transplantation was the cost of medications. Total cost was higher for living-donor transplantation (USD 22,986.60+/- 1,477.09) than for cadaveric transplantation (USD 21,582.90+/- 1,818.11) (p= 0.0022). CONCLUSIONS: Total cost of living-donor liver transplantation is higher than that of cadaveric transplantation.

Adult↗
PubMed2003

Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of May 2003.

As of December 31, 2003, more than 21,000 pancreas transplants had been reported to the IPTR, >15,000 in the US and >5,000 outside the US. An era analysis of US cases from 1987 to May 15, 2003 showed a progressive improvement in outcome (p<0.04), with pancreas transplant graft survival rates (GSRs) going from 76% at one year for 1987-92 to 85% for 2001-2003 SPK cases, from 57%-79% for PAK cases, and from 55%-76% for PTA cases. The improvements were due both to decreases in technical failure rates (from 15%-10% in SPK, 21%-13% in PAK, and 24%-8% in PTA) and immunological failure rates (going from 6%-1% for SPK, from 23%-4% for PAK, and from 28%-7% for PTA cases). The proportion of recipients >45 years old increased from 11% in all 3 recipient categories in 1987-92 to 32-36% for 2001-2003 cases, and the improved outcomes encompassed the older patients as well. Contemporary pancreas transplant outcomes were calculated separately for January 1, 1999- May 15, 2003 US and non-US cases. The results of the US analysis are summarized first. US patient survival rates at one year were >95% in each recipient category, with one-year primary pancreas GSRs of 85% for SPK (n=3,775), 79% for PAK (n=951), and 78% for PTA (n=403) (p<0.0001). The immunological graft failure rates for 1996-2002 technically successful SPK, PAK and PTA cases were 2% (n=3,437), 5% (n=854), and 7% (n=356) at one year (p=0.0001). There was a progressive increase in the use of ED (as opposed to BD) for duct management. For 1999-2003 US primary pancreas transplants, ED was used in 78% of SPK, 60% of PAK and 49% for PTA cases. Of the ED transplants, venous drainage via the portal system was used for 23% of SPK, 27% of PAK and 44% of PTA cases. Pancreas GSRs were nearly identical for 1999-2003 ED (n=2,898) and BD (n=798) SPK transplants (85% for both at one year), nor was there a significant difference (p>0.17) in pancreas GSRs for systemic (n=2,218) versus portal (n=680) venous drained ED SPK transplants (84% vs 87% at one year). Kidney GSRs were not significantly different for ED versus BD SPK cases, 93% and 92% at one year (p=0.24). Pancreas GSRs for PAK transplants were 82% at one year for BD (n=360; all systemic venous drainage) versus 77% for ED with systemic (n=398) versus 74% for ED with portal (n=150) venous drainage (p=0.03 overall, and 0.02 for ED portal vs ED systemic). For PTA cases, one-year GSRs were 81% with BD (n=196; all systemic venous drainage) versus 69% for ED with systemic (n=99) versus 80% for ED with portal (n=90) venous drainage (p > or = 0.08 overall, and 0.11 for ED portal vs ED systemic). BD transplants were associated with a 12-14% conversion rate to ED by 2 years after transplantation in the 3 recipient categories. The age of US pancreas transplant recipients made little difference for outcome in the SPK category, with one-year pancreas GSRs ranging from 80-85% for patients grouped by age in decades from 10-19 to 60-69 years. In the PAK category, one-year GSRs tended to increase with age, going from 71% for those 20-29 to 89% for those 60-69 years old. Likewise, in the PTA category one-year GSRs were higher in older than younger donors, age, being only 50% in 10-19 year-old and 87% in 40-49 year-old recipients. Pancreas GSRs were identical (85% at one year) for 1999-2003 US SPK recipients reported to have Type 1 (n=3,479) or Type 2 (n=231) diabetes (6% classified as Type 2). TAC+MMF was the dominant maintenance immunosuppressant for 1999-2003 US cases (approximately two-thirds) and with this regime one-year GSRs were >81% in all 3 recipient categories. The results were very similar (> or = 79% one-year GSR) in patients (approximately 10%) treated with sirolimus under various protocols. HLA-B locus matching had a significant effect on pancreas transplant outcome in the PTA category. For 1999-2003 cases the one-year rejection loss rate was 15% in recipients mismatched for 2 B-locus antigens (n=28) versus 3% and 4% for those mismatched for one (n=114) or zero (n=82) antigens. The proportion of 1999-2003 US pancreas grafts that were retransplants was <2% in the SPK and only 9% in the PTA categories, but 23% in the PAK category. The majority of the latter were done after isolated failure of a pancreas graft in SPK recipients. Pancreas retransplant GSRs at one year were 69% in the SPK (n=60), 77% in the PAK (n=288) and 73% in the PTA (n=39) categories, significantly lower than for primary grafts only in the SPK category (p=0.001). In regard to non-US pancreas transplants, even in 1999-2003 the overwhelming majority were in the SPK category (n=1,833), with one-year patient, kidney and pancreas survival rates of 98%, 94% and 89%, slightly but significantly higher than those for US cases done during the same period. Non-US PAK (n=55) GSR at one year was 88%, similar to that for US cases done during this period, but the non-US PTA (n=80) GSR at one year was lower at 66%. In summary, with modern immunosuppression (TAC + MMF for maintenance) 1999-2003 US pancreas transplant graft survival rates were > or = 80% at one year in all categories of recipients (SPK, PAK, PTA), as was the case for non-US SPK and PAK transplants.

Demography↗
PubMed2006

The high integration and differentiation potential of autologous neural stem cell transplantation compared with allogeneic transplantation in adult rat hippocampus.

Cell therapy is thought to have a central role in restorative therapy, which aims to restore function to the damaged nervous system. The purpose of this study was to establish an autologous neural stem cell (NSC) transplantation model using adult rats and to compare survival, migration, and differentiation between this system and allogeneic NSC transplantation. Furthermore, we compared the immunologic response of the host tissue between autologous and allogeneic transplantation. NSCs were removed from the subventricular zone of adult Fischer 344 rats using stereotactic methods. NSCs were expanded and microinjected into normal hippocampus in the autologous brain. Allogeneic NSC (derived from adult Wistar rats) transplantation was performed using the same procedure, and hippocampal sections were analyzed immunohistologically 3 weeks post-transplantation. The cell survival and migration rate were higher for autologous transplantation than for allogeneic transplantation, and the neuronal differentiation rate in the autologous transplanted cells far exceeded that of allogeneic transplantation. Furthermore, there was less astrocyte and microglia reactivity in the host tissue of the autologous transplantation compared with allogeneic transplantation. These findings demonstrate that immunoreactivity of the host tissue strongly influences cell transplantation in the CNS as the autologous transplantation did not induce host tissue immunoreactivity; the microenvironment was essentially maintained in an optimal condition for the transplanted cells.

Animals↗
PubMed2000

Haematopoietic stem cell transplantation for patients with myelo-dysplastic syndromes and secondary acute myeloid leukaemias: a report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

Allogeneic stem cell transplantation from an HLA-identical sibling donor is a curative treatment option for a young patient with myelodysplastic syndrome, limited by age and lack of sibling donors. Alternative stem cell sources have been used more recently, such as unrelated donors, non-identical family members or autologous transplants. This analysis of 1378 transplants reported to the European Group for Blood and Marrow Transplantation (EBMT) addresses the outcome of the varying procedures according to the known risk factors. The estimated disease-free survival (DFS) and estimated relapse risk at 3 years were both 36% for 885 patients transplanted with stem cells from matched siblings. In the multivariate analysis, age and stage of disease had independent prognostic significance for DFS, survival and treatment-related mortality. Patients transplanted at an early stage of disease had a significantly lower risk of relapse than patients transplanted at more advanced stages. The estimated DFS at 3 years was 25% for the 198 patients with voluntary unrelated donors, 28% for the 91 patients with alternative family donors and 33% for the 126 patients autografted in first complete remission. The non-relapse mortality was 58% for patients with unrelated donors, 66% for patients with non-identical family donors and 25% for autografted patients. The relapse rate of 18% was relatively low for patients with non-identical family donors, 41% for patients with unrelated donors and 55% for patients treated with autologous stem cell transplantation. Both allogeneic and autologous stem cell transplantation have emerged as treatment options for patients with myelodysplastic syndromes. Transplantation with an HLA-identical sibling donor is the preferred treatment option. Patients without an HLA-identical sibling donor may be treated with either autologous stem cell transplantation or an alternative donor transplantation. Patients younger than 20 years may be treated with an unrelated donor transplantation. Patients older than 40 years, and probably also patients between 20 and 40 years, may benefit most from an autologous stem cell transplantation.

Actuarial Analysis↗
PubMed1996

Incidence of post-transplant malignancy among 674 solid-organ-transplant recipients at a single center.

We evaluated the post-transplant course of the entire solid-organ-transplant population at our institution to determine the frequency, incidence and specific type of post-transplant malignancies which occurred at a single center. Of 674 solid-organ-transplant recipients (305 renal, 307 heart, 54 lung, 8 heart/lung), we detected 79 malignancies (48 heart, 28 renal, 2 lung, 1 heart/lung), representing an overall cancer frequency of 11.7%, 15.6% for heart and 9.2% for renal transplant recipients. The frequency in both transplant groups was higher than that reported previously in the multicenter data in the literature (about 6%); we also noted a shorter interval to malignancy (27 vs. 61 months). The most common malignancies overall were skin/lip carcinomas and post-transplant lymphoproliferative disorder (PTLD). The frequency of PTLD was higher in non-renal (6.5%) than renal (0.7%) transplant recipients and statistical analysis confirmed a significant higher incidence of all malignancies (p = 0.0032) and of PTLD (p = 0.0001) in heart and lung recipients as opposed to renal transplant recipients. The frequency of total skin/lip carcinomas was essentially equal in the heart and renal transplant groups (6%), and statistical analysis showed no significant difference in incidence of this general type of malignancy; however, there was a marked disparity in interval to squamous cell carcinoma (SCC) between renal and heart transplant recipients (27 versus 59 months). This was associated with an apparent increase in the rate of occurence of SCC after 60 months in heart transplant recipients, a finding not previously reported in the multicenter data in the literature. We did not demonstrate a significant effect of the withdrawal of prophylactic OKT3 from the immunosuppression regimen of heart transplant recipients on the incidence of all tumors, PTLD or skin/lip tumors.

Aged↗
PubMed1984

Transplantation of tectal tissue in rats. IV. Maturation of transplants and development of host retinal projection.

We have examined the time course of maturation of embryonic tectal tissue transplanted to the midbrain region of newborn rats and studied the development of the host retinal projection to the grafts. Transplants were examined 2-19 days after transplantation. The morphology of developing transplants was studied using Holmes silver and neutral red stained material. Tectal transplants attained their mature morphology about 17 days after transplantation. The time course of tectal transplant maturation appeared to be similar to that of normal superior colliculus in situ. The development of the host retinal projection into the transplants was examined by injecting the host eyes with horseradish peroxidase (HRP) at various times after transplantation. Retinal fibers anterogradely labeled with HRP were first seen growing into the transplants 3-4 days after transplantation. Ingrowing fibers were always located close to the surface of the transplants. The rate of growth of optic axons into the grafts was estimated to be about 250 to 300 micron per day. Patch-like arborizations of retinal afferents were formed soon after innervation and the mature pattern of optic innervation was established by about two weeks. There was no evidence for an initial transitory phase in which the axons invaded the whole transplant. The development of the host retinal projection preceded morphological maturation of the transplants. The mode of ingrowth of retinal axons into tectal grafts was in many respects similar to the way optic fibers grow into the superior colliculus during normal in situ development. The transplant technique thus provides an opportunity to manipulate and analyze the factors which guide optic fiber growth in intact brains.

Animals↗
PubMed1999

Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry.

BACKGROUND AND METHODS: It is uncertain whether mortality rates among patients who have undergone bone marrow transplantation return to the level of the mortality rates of the general population. We analyzed the characteristics of 6691 patients listed in the International Bone Marrow Transplant Registry. All the patients were free of their original disease two years after allogeneic bone marrow transplantation. Mortality rates in this cohort were compared with those of an age-, sex-, and nationality-matched general population. Cox proportional-hazards regression was used to identify risk factors for death more than two years after transplantation (late death). RESULTS: Among patients who were free of disease two years after transplantation, the probability of living for five more years was 89 percent (95 percent confidence interval, 88 to 90 percent). Among patients who underwent transplantation for aplastic anemia, the risk of death by the sixth year after transplantation did not differ significantly from that of a normal population. Mortality remained significantly higher than normal throughout the study among patients who underwent transplantation for acute lymphoblastic leukemia or chronic myelogenous leukemia and through the ninth year among those who underwent transplantation for acute myelogenous leukemia. Recurrent leukemia was the chief cause of death among patients who received a transplant for leukemia, whereas chronic graft-versus-host disease was the chief cause among those who received a transplant for aplastic anemia. Advanced, long-standing disease before transplantation and active chronic graft-versus-host disease were important risk factors for late death. CONCLUSIONS: In patients who receive an allogeneic bone marrow transplant as treatment for acute myelogenous or lymphoblastic leukemia, chronic myelogenous leukemia, or aplastic anemia and who are free of their original disease two years later, the disease is probably cured. However, for many years after transplantation, the mortality among these patients is higher than that in a normal population.

Adolescent↗
PubMed1997

Delaying transplantation after total body irradiation is a simple and effective way to reduce acute graft-versus-host disease mortality after major H2 incompatible transplantation.

BACKGROUND: We have previously reported that delaying histoincompatible transplantation after total body irradiation (TBI) conditioning markedly decreased the mortality of acute graft-versus-host disease (GVHD) in severe combined immunodeficiency mice. However, it was not clear whether the delayed transplantation would affect the final engraftment and acute GVHD mortality in normal hosts. METHODS: BALB/c mice (H2d) were lethally irradiated with 8.5 Gy TBI and transplanted with C57BL/6 (H2d) bone marrow plus spleen cells on the same day (TBI+day 0) or 4 days after TBI conditioning (TBI+day 4). RESULTS: We again demonstrated that delaying transplantation by 4 days after TBI conditioning markedly reduced acute GVHD mortality in normal hosts after major histoincompatible transplantation. The survival rates were 66% in TBI+day 4 vs. 0% in TBI+day 0 allogeneic transplanted animals by day +60 (P<0.001). Further analysis demonstrated that the 4-day rest between the TBI and allogeneic transplantation broke the interaction of cell/inflammatory tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-6 cytokine reactions stimulated by TBI and incompatible transplantation. Flow cytometry revealed 97% donor cells in host marrow by 2 weeks in TBI+day 0 transplantation versus 57% in TBI+day 4 transplantation. There was no difference in percentage of donor CD3+ T-cell engraftment between the TBI+day 0 and TBI+day 4 allogeneic transplanted animals. In TBI+day 4 transplantation, the percentage of donor cells in host marrow steadily increased to 74% by day +60 and 93% by day +100. CONCLUSIONS: This 2- to 3-month early mixed chimerism in TBI+day 4 transplanted animals might be related to lower levels of tumor necrosis factor-alpha and IL-6 both of which have been shown to stimulate lymphohematopoiesis and was associated with lower acute GVHD mortality. The data again demonstrated in immunologically normal BALB/c mice that delaying allogeneic transplantation after TBI is a simple and effective way to reduce acute GVHD mortality, achieve satisfactory engraftment and significantly increase overall survival.

Animals↗
PubMed1998

Prognosis after primary renal transplant failure and the beneficial effects of repeat transplantation: multivariate analyses from the United States Renal Data System.

BACKGROUND: Survival of transplant recipients after primary renal allograft failure has not been well studied. METHODS: A cohort of 19,208 renal transplant recipients with primary allograft failure between 1985 and 1995 were followed from the date of allograft loss until death, repeat transplantation, or December 31, 1996. The mortality, wait-listing, and repeat transplantation rates were assessed. The mortality risks associated with repeat transplantation were estimated with a time-dependent survival model. RESULTS: In total, 34.5% (n=6,631) of patients died during follow-up. Of these deaths, 82.9% (n=5,498) occurred in patients not wait-listed for repeat transplantation, 11.9% (n=789) occurred in wait-listed patients, and 5.2% (n=344) occurred in second transplant recipients. Before repeat transplantation, the adjusted 5-year patient survival was 36%, 49%, and 65% for type I diabetes mellitus (DM), type II DM, and nondiabetic end-stage renal disease, respectively (P<0.001; DM vs. nondiabetics). The adjusted 5-year patient survival was lower in Caucasians (57%, P<0.001) compared with African-Americans (67%) and other races (64%). The 5-yr repeat transplantation rate was 29%, 15%, and 19%, whereas the median waiting time for a second transplant was 32, 90, and 81 months for Caucasians, African-Americans, and other races, respectively (P<0.0001 each). Repeat transplantation was associated with 45% and 23% reduction in 5-year mortality for type I DM and nondiabetic end-stage renal disease, respectively, when compared with their wait-listed dialysis counterparts with prior transplant failure. CONCLUSIONS: The loss of a primary renal allograft was associated with significant mortality, especially in recipients with type I DM. Repeat transplantation was associated with a substantial improvement in 5-year patient survival. Recipients with type I DM achieved the greatest proportional benefit from repeat transplantation.

Adolescent↗
PubMed2004

Successful renal transplantation following prior bone marrow transplantation in pediatric patients.

Improving survival rates following pediatric bone marrow transplantation (BMT) will likely result in greater numbers of children progressing to end-stage renal disease (ESRD) because of prior chemotherapy, irradiation, sepsis, and exposure to nephrotoxic agents. Renal transplantation remains the treatment of choice for ESRD; however, the safety of renal transplantation in this unique population is not well established. We report our experience with living related renal transplantation in three pediatric patients with ESRD following prior BMT. Two patients with neuroblastoma and ESRD because of BMT nephropathy, and one patient with Schimke immuno-osseous dysplasia and ESRD because of immune complex mediated glomerulonephritis and nephrotic syndrome. Age at time of BMT ranged from 2 to 7 yr. All patients had stable bone marrow function prior to renal transplantation. Age at renal transplant ranged from 8 to 14 yr. All three patients have been managed with conventional immunosuppression, as no patient received a kidney and BMT from the same donor source. These patients are currently 7 months to 6 yr status post-living related transplant. All have functioning bone marrow and kidney transplants, with serum creatinine levels ranging 0.6-1.2 mg/dL. There have been no episodes of rejection. One patient with a history of grade III skin and grade IV gastrointestinal-graft-vs.-host disease (GI-GVHD) prior to transplantation, had a mild flare of GI-GVHD (grade I) post-renal transplant and is currently asymptomatic. The incidence of opportunistic infection has been comparable with our pediatric renal transplant population without prior BMT. One patient was treated for basal cell carcinoma via wide local excision. Renal transplantation is an excellent option for the treatment of pediatric patients with ESRD following BMT. Short-term results in this small population show promising patient and graft survival, however long-term follow-up is needed. Pre-existing immune system impairment and bone marrow function should be taken into consideration when weighing different immunosuppressive agents for renal transplantation. Patients who have undergone renal transplantation following BMT are at high risk for opportunistic infections and malignancy, and need life-long medical surveillance.

Adolescent↗
PubMed2000

Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT).

Peripheral blood cells are increasingly used in place of bone marrow as a source of hematopoietic stem cells for allogeneic transplantation. The relative efficacy of these 2 approaches is unknown. This retrospective multivariate analysis compared results of 288 HLA-identical sibling blood stem cell transplantations with results of 536 HLA-identical sibling bone marrow transplantations. No transplants were T-cell depleted. Median follow-up was 12 months, and analyses focused on 1-year outcomes. Recipients of blood stem cell transplants had more rapid recovery of neutrophils to at least 0.5 x 10(9)/L (median time to recovery, 14 days, compared with 19 days for marrow transplants; P <.001) and of platelets to at least 20 x 10(9)/L (median time, 18 days, compared with 25 days for marrow transplants; P <.001). There was no significant difference in the incidence of grades II to IV acute graft versus host disease (GVHD). The incidence of chronic GVHD was significantly higher after blood stem cell transplantation (1-year probability [95% confidence interval], 65% [56%-72%] compared with 53% [47%-59%]; P =.02) Relapse incidence in the 2 transplant groups did not differ significantly. Treatment-related mortality rates were lower and leukemia-free survival rates were higher with blood stem cell transplants in patients with advanced leukemia (acute leukemia in second remission or chronic myelogenous leukemia in accelerated phase) but not in early leukemia (acute leukemia in first remission or chronic myelogenous leukemia in chronic phase). The median time from transplantation to hospital discharge was 23 days after blood stem cell transplantation and 28 days after bone marrow transplantation (P =.003). Further study with longer follow-up is necessary to definitively establish the role of blood stem cells for allogeneic transplantation, especially in patients with good-risk disease. (Blood. 2000;95:3702-3709)

Acute Disease↗