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PubMed2005

Analysis of factors that influence survival with post-transplant lymphoproliferative disorder in renal transplant recipients: the Israel Penn International Transplant Tumor Registry experience.

Significant mortality is associated with post-transplant lymphoproliferative disorder (PTLD) in kidney transplant recipients (KTX). Univariate/multivariate risk factor survival analysis of US PTLD KTX reported to Israel Penn International Transplant Tumor Registry from November 1968 to January 2000 was performed. PTLD presented 18 (median) (range 1-310) months in 402 KTX. Death rates were greater for those diagnosed within 6 months (64%) versus beyond 6 months (54%, p = 0.04). No differences in death risk for gender, race, immunosuppression, EBV, B or T cell positivity were identified. Death risk increased for multiple versus single sites (73% vs. 53%, hazards ratio (HR) 1.4). A 1-year increase in age increased HR for death by 2%. Surgery was associated with increased survival (55% vs. 0% without surgery) (p < 0.0001). Patients with allograft involvement, treated with transplant nephrectomy alone (n = 20), had 80% survival versus 53% without allograft removal (n = 15) (p < 0.001). Overall survival was 69% for allograft involvement alone versus 36% for other organ involvement plus allograft (n = 19 alive) (p < 0.0001). Death risk was greater for multiple site PTLD and increasing age, and risks were additive. Univariate analysis identified increased death risk for those not receiving surgery, particularly allograft involvement alone.

Graft Rejection↗
PubMed2000

Post-transplant lymphoproliferative disorders (PTLD) after renal transplantation: management and evolution of seven cases among 1002 renal transplants in São Paulo, Brazil.

We reported seven cases (0.7%) of PTLD among 1002 renal transplants performed at Renal Transplant Service from Hospital São Paulo-Universidade Federal de São Paulo/Escola Paulista de Medicina, São Paulo, Brazil, between 1976 and 1997. There were three male and four female patients with median age of 37 year-old. According to Ann Arbor staging system there were four localized extra-nodal intermediate-grade NHL, one disseminated low-grade NHL and two polyclonal lymphoid hyperplasia. Four patients received cadaveric, two received related and one received unrelated renal transplant. PTLD occurred after a median latency period of 36 months (ranging from 5 to 84 months). In situ hybridization for EBER1 was performed in five patients and molecular evidence of EBV was found in 3 cases (two DLCL and one lymphoplasmocytoid lymphoma). All patients were treated with immunosuppression withdrawal, four patients received anthracyclin-based chemotherapy for control of localized or systemic clonal disease and three were treated with resection of primary PTLD. Four of seven patients (57%) are in complete remission 11, 20, 25 and 79 months after PTLD onset. One patient lost follow-up and two patients died due to lymphoma relapse, respectively 4 and 10 months after completion of treatment. In conclusion, our experience with this small group of patients showed that: 1) immunosuppression withdrawal is not necessarily associated with loss of renal transplant and can be used as the only treatment for polyclonal PTLD; 2) chemotherapy can simultaneously lead to clonal PTLD remission and periodic immunosuppression, avoiding graft rejection after immunosuppression withdrawal.

Adult↗
PubMed1996

[Indications, contraindications and differential therapeutic alternatives in heart transplantation. Current status and results of a survey by the German Transplantation Programs. Thoracic Organ Transplantation Study Group of the German Society of Cardiology--Heart and Lung Research].

In conjunction with the report on "Posttransplant care and rehabilitation", the consensus paper on "Indications, contraindications, and therapeutic alternatives to cardiac transplantation" reflects the current practice in German cardiac transplant centers. This paper is based on a survey organized in 1994 by the Working Group on Thoracic Organ Transplantation of the German Society of Cardiology in which all German transplant centers participated.

Combined Modality Therapy↗
PubMed2002

Application of peripheral blood stem cells (PBSC) mobilized by recombinant human granulocyte colony stimulating factor for allogeneic PBSC transplantation and the comparison of allogeneic PBSC transplantation and bone marrow transplantation.

Recombinant human granulocyte colony stimulating factor (rhG-CSF)-mobilized peripheral blood stem cells (PBSC) are now widely used for allogeneic PBSC transplantation (alloPBSCT). Large numbers of hematopoietic progenitor cells mobilized by rhG-CSF would be considered equivalent or better than bone marrow (BM) cells and would be used as an alternative to BM for allogeneic hematopoietic stem cell transplantation. The complications associated with the administration of rhG-CSF and apheresis in PBSC collection in formal donors are well tolerated and usually acceptable in the short term but some hazardous adverse events such as splenic rupture and cardiac arrest are reported although the incidence is very low. Protective means and stopping rules for safe donation in the collection of PBSC are established. The characteristics of PBSC were clarified; the expression of some adhesion molecules such as CD49d on CD34 positive cells of PBSC have been shown to be low compared to BM stem cells. In alloPBSCT compared with allogeneic BM transplantation (alloBMT), the incidence and frequency of graft versus host disease (GVHD) is of concern because high number of T lymphocytes are infused in alloPBSCT. The incidence and severity of acute GVHD are not increased but chronic GVHD is higher in alloPBSCT compared with alloBMT. The outcome of alloPBSCT and BMT are almost equivalent and conclusive results regarding survival are not yet available.

Blood Cells↗
PubMed2000

Hospital capacity and post-transplant survival after allogeneic bone marrow transplantation: analysis of data from the Japan Society for Hematopoietic Cell Transplantation.

The association between hospital capacity and survival after allogeneic bone marrow transplantation (allo-BMT) was examined using the dataset accumulated by the Japan Society of Hematopoietic Cell Transplantations (JSHCT). The subjects were 3134 patients who received first allo-BMTs between 1991 and 1997 reported to the JSHCT. They were divided into three groups by cumulative hospital experience of allo-BMTs: low volume (capacity) (LV; < or = 25 cases), moderate volume (capacity) (MV; 26-75 cases) and high volume (capacity) (HV; > or = 76 cases). Using a proportional hazards model, the association of hospital experience with early survival at day 100 (D100S), and overall survival (OS) were examined. For leukemia patients, leukemia-free survival (LFS) was also analyzed. When HV was defined as the reference group, the hazard ratios (HRs) of OS for all subjects were 1.10 (95% confidence interval; 0.97-1.25) for MV and 1.25 for LV (1.08-1.44). The HRs with D100S were 1.20 (0.96-1.51) for MV and 1.40 (1.08-1.80) for LV. Larger values were observed for OS and D100S in cases of leukemia. Survival after BMT from sibling donors was clearly influenced by hospital experience, but this was not the case from unrelated donors. These findings suggest that size of the transplant team should be considered in order to improve the outcome of sibling BMT in general.

Adolescent↗
PubMed2006

Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006: transplant activity, long-term data and current results. An analysis by the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

The introduction of imatinib mesylate has changed attitudes towards hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML). Information on the current use and results of HSCT is warranted. Data from 592 teams in 42 European countries described their use of HSCT for CML from 1990 to 2004. Outcomes were analyzed for 13,416 patients, with a median age of 36 years (range 1-71 years); 60% were male. The analysis considered three time cohorts, 1980 to 1990, 1991 to 1999 and 2000 to 2003. Survival, transplant-related mortality and relapse incidence were assessed at 20 years for the first cohort and compared at 2 years between the three cohorts. The numbers of HSCT for CML increased from 540 allogeneic HSCT in 1990 to 1,396 HSCT in 1999 and declined to 802 in 2004. One third of all patients and half of those with a low risk were alive at 20 years. Survival at 2 years has improved from 53% to 61% in the most recent years due to a reduction in transplant-related mortality from 41% to 30% in all patients and from 31% to 17% in low-risk patients. Stage, donor type, time interval, age and donor-recipient sex combination remain the main risk factors; patients with a risk score of 0 or 1 have a survival probability of 80% at 2 years. HSCT remains an important treatment option for patients with CML. The data describe the current status of this option and the outcome a patient can expect today. They provide an objective basis for decision making.

Adolescent↗
PubMed2000

Current results of bone marrow transplantation in patients with acquired severe aplastic anemia. Report of the European Group for Blood and Marrow transplantation. On behalf of the Working Party on Severe Aplastic Anemia of the European Group for Blood and Marrow Transplantation.

We have analyzed 2,002 patients grafted in Europe between 1976 and 1998 from an identical twin (n = 34), from an HLA-identical sibling (n = 1,699) or from an alternative donor (n = 269), which included unrelated and family mismatched donors. The proportions of patients surviving in these three groups are, respectively, 91, 66 and 37%: major causes of failure were acute graft-versus host disease (GvHD) (11%), infection (12%), pneumonitis (4%), rejection (4%). In multivariate Cox analysis, factors predicting outcome were patient's age (p < 0.0001), donor type (p < 0.0001), interval between diagnosis and bone marrow transplantation (BMT) (p < 0.0005), year of BMT (p = 0.0005) and female donor for a male recipient (p = 0.02). Patients were then divided in two groups according to the year of BMT: up to or after 1990. The overall death rate dropped from 43 to 24% (p < 0.00001). Improvements were seen mostly for grafts from identical siblings (from 54 to 75%, p < 0.0001), and less so for alternative-donor grafts (from 28 to 35%; p = 0.07). Major changes have occurred in the BMT protocol: decreasing use of radiotherapy in the conditioning regimen (from 35 to 24%; p < 0.0001) and increasing use of cyclosporin (with or without methotrexate) for GvHD prophylaxis (from 70 to 98%; p < 0.0001). In conclusion, the outcome of allogeneic BMT for patients with severe aplastic anemia has considerably improved over the past two decades: young patients, grafted early after diagnosis from an identical sibling, have currently an over 80% chance of long-term survival. Transplants from twins are very successful as well. The risk of complications with alternative donor transplants is still high.

Acute Disease↗
PubMed1990

Transplantation in patients with diabetic nephropathy. Outcome of combined pancreas and kidney transplantation compared with kidney transplantation only.

Detailed results of 12 combined pancreas and kidney transplantations (Comb) were compared with those of two matched diabetic controls per patient--one living donor kidney recipient (LD) and one cadaveric donor kidney recipient (CD--who, though eligible for pancreas transplantation also, preferred kidney transplantation only. Mean follow-up was 22, 23, and 21 months in the three groups. There was no mortality in the LD group, but two CD and one Comb patient died from cardiovascular disease. Two kidneys were lost in both the Comb and the LD group, compared to five in the CD group. Ten major vascular events occurred and three of them were lethal. The only LD case was one below-knee amputation; the other nine were equally distributed in the Comb and CD groups. The time spent in the hospital was shorter for the LD group. Thus, in the short run, LDs confer the best results, whereas in the long term the better metabolic control in the Combs may prove favorable.

Adult↗
PubMed2004

Myeloablative allogeneic hematopoietic stem cell transplantation in patients who experience relapse after autologous stem cell transplantation for lymphoma: a report of the International Bone Marrow Transplant Registry.

Myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly used in patients with lymphoma who experience disease relapse after autologous hematopoietic stem cell transplantation (auto-HSCT) because the allograft is tumor free and may induce a graft-versus-tumor effect. We analyzed 114 patients treated with this approach from 1990 to 1999 to assess disease progression, progression-free survival (PFS), and overall survival (OS). Cumulative incidence of disease progression at 3 years was 52%, whereas treatment-related mortality was 22%, lower than previously reported. Three-year probabilities of OS and PFS were 33% and 25%, respectively. With prolonged follow-up, however, nearly all patients experienced disease progression, and 5-year probabilities were 24% and 5%, respectively. Complete remission at the time of allo-HSCT and use of total body irradiation (TBI) in patients with non-Hodgkin lymphoma (NHL) were associated with lower rates of disease progression and higher rates of OS. In summary, allo-HSCT is feasible for patients with lymphoma who have relapses after auto-HSCT and can result in prolonged survival for some, but it is usually not curative. Most likely to benefit are patients who have HLA-matched sibling donors, are in remission, and have good performance status.

Adolescent↗
PubMed1995

Reduced size liver transplantation, split liver transplantation, and living related liver transplantation in relation to the donor organ shortage.

Because of the shortage of cadaveric donors, three techniques of partial liver grafting have been developed. These techniques are placed in perspective in relation to the organ shortage. Reduced size liver transplantation (RSLTx) is widely used and has results comparable to those from whole liver grafting. However, this technique, while benefitting pediatric patients, reduces the adult donor liver pool. It also makes inefficient use of an available adult donor liver. In split liver transplantation (SPLTx), the whole liver is used after bipartition for two recipients. The results are comparable to those of RSLTx. The problem with SPLTx is that it is a very demanding technique applied only in centers with extensive experience with liver resection and reduction. Living related liver transplantation (LRLTx) yields excellent results; however, it places an otherwise healthy person at risk. It is argued that instead of performing risky operations on healthy persons, the health authorities should take specific measures to alleviate the organ shortage. In the meantime, SPLTx should be developed further because of its optimal use of donor tissue. As for LRLTx, its excellent results and the present shortage of size-matched pediatric liver donors justify its use, at least for now.

Adult↗
PubMedDate not supplied

Heart transplantation in children after mechanical circulatory support: comparison of heart transplantation with ventricular assist devices and elective heart transplantation.

Heart transplantation (HTx) is an ultimate treatment for children with end-stage heart failure or inoperable congenital heart disease. The supply of hearts is inadequate; therefore, different mechanical support systems must be used as bridge to HTx in pediatric patients with postoperative low output. The use of ventricular assist devices (VADs) as bridge to HTx in children is limited because of size differences. The purpose of this study was to evaluate the overall long-term outcome of pediatric circulatory support before pediatric HTx. From 1989 through 2004, 91 pediatric patients underwent isolated HTx. Seven of them required mechanical support before transplantation. We reviewed retrospectively the course of 91 children (mean age 14.7 years) who underwent HTx. Group A consisted of elective HTx patients who were treated as outpatients before HTx, whereas group B was the VAD-HTx bridging group (n=7; mean age 12.31 +/- 2.8 years). Mean duration of VAD support was 108 +/- 98 days (minimum 1 day, maximum 258 days). Overall survival rate after HTx was 80% at 1 year without significant differences between groups. Five of seven patients survived and could be discharged after successful HTx, for a survival rate of 77%. The mean follow-up period was 16.76 +/- 10.6 months. No differences in posttransplantation long-term survival and rejection episodes occurred between patients transplanted with or without VAD. VAD therapy can keep pediatric patients with end-stage heart failure alive until successful HTx, and bridge to HTx is a safe procedure in pediatric patients. After HTx, survival rates of these children are similar to those of patients awaiting elective HTx.

Adolescent↗
PubMedDate not supplied

Infections in heart transplant recipients: the experience of the Italian heart transplantation program. Italian Study Group on Infections in Heart Transplantation.

Infectious complications are an important cause of morbidity and mortality in heart transplantation. In this report we describe their incidence in the Italian Heart Transplantation Program and their relationship to induction immunosuppressive protocols used. A total of 662 heart transplantations in 651 patients had been performed by March 1, 1990, in 10 Italian centers, with a follow-up of 12,022 patient-months. Actuarial survival at 54 months was 80%. There were 115 deaths, 28 as a result of infection (24%); 30 were perioperative. Mortality from infection was 15% in the first 30 postoperative days and 35% thereafter. During follow-up, 256 life-threatening infectious episodes occurred in 180 patients, for a mean of 1.42 infections/patient. Of these episodes, 28 (10.9%) were lethal. The rate at 54 months, excluding perioperative deaths, was 0.021 episodes/patient-month, with a mean of 0.39 infections/patient in the 651-patient series. At 6 months, 72% of patients were free from infection. This value did not change significantly during subsequent follow-up. Bacterial infections were most frequent (49.2%); fungal (10.5%) and protozoan (5.9%) infections had the worst outcome (lethality 26% and 20%, respectively). A primary cytomegalovirus infection was observed in 23 cases (12 mismatches). Lung involvement (99 episodes) and bacterial sepsis (47 episodes) were most common. Eighty episodes of infection (31.2%) were preceded by a supplementary treatment for rejection with steroid pulses (69%), prednisone boost (20%), or cytolytic therapy (11%). Treatment had preceded the infection by less than 15 days in 55% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart Transplantation↗
PubMed1978

Dynamic renal transplant imaging with Tc-99m DTPA (Sn) supplemented by a transplant perfusion index in the management of renal transplants.

We have performed 955 studies on 152 patients with 167 renal transplants. Images were recorded following bolus injection of 12-15 mCi Tc-99m DTPA (Sn). The data were stored on a computer and analyzed by generation of region-of-interest curves from (a) the iliac artery distal to the transplant, (b) the kidney, and (c) a background area. A perfusion index was adopted: formula see text. In 276 studies the patient clearly had acute tubular necrosis (ATN), rejection, or a normal kidney on retrospective analysis. The normal perfusion index has a value below 150, and it increases with falling perfusion, such as is seen in rejection and in renal-artery stenosis. The use of this index in addition to sequential images and changes in the region-of-interest curves usually allows separation of rejection from ATN and, particularly, rejection from normals. When serial studies are performed, the separation of rejecting from nonrejecting transplants is excellent, although renal-artery stenosis may cause similar changes in perfusion.

Acute Kidney Injury↗
PubMed2006

Use of G-CSF in matched sibling donor pediatric allogeneic transplantation: a consensus statement from the Children's Oncology Group (COG) Transplant Discipline Committee and Pediatric Blood and Marrow Transplant Consortium (PBMTC) Executive Committee.

Preliminary studies indicate that G-CSF-primed marrow harvesting may result in a graft with increased mononuclear cells collected, increased CD34(+) stem and progenitor cell dose and a potential for more rapid engraftment. Increased cell dose plus other potential positive effects of G-CSF priming have resulted in improved survival in non-randomized preliminary studies. These benefits may be available without the increased risk of chronic graft versus host disease (GVHD) that is experienced with allogeneic peripheral blood stem cell (PBSC) transplant. A phase III Children's Oncology Group (COG)/Pediatric Blood and Marrow Transplant Consortium (PBMTC) trial comparing G-CSF-primed marrow to standard marrow has been proposed. This document reviews background studies of G-CSF-primed marrow and addresses benefits and risks of G-CSF administration to normal pediatric donors. We conclude that the approach is promising and warrants further study. Risks of G-CSF to the donor are minimal and benefits to both donor and recipient may occur.

Child↗
PubMed2002

European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.6.2. Cancer risk after renal transplantation. Skin cancers: prevention and treatment.

GUIDELINES: D. Due to the high prevalence of skin cancers after organ transplantation, it is highly recommended to inform patients about self-awareness. E. Primary prevention should include the avoidance of sun exposure, use of protective clothing and use of an effective sunscreen (protection factor >15) for unclothed body parts (head, neck, hands and arms) in order to prevent the occurrence of squamous-cell carcinoma. This is the most frequent skin tumour in transplant recipients, and its preferential location is the head. F. Recipients with pre-malignant skin lesions (warts, epidermodysplasia verruciformis or actinic keratoses) should be referred early to a dermatologist for active treatment and close follow-up. G. All skin cancers should be completely removed by a dermatologist with appropriate techniques, such as electro-desiccation with curettage, cryotherapy or surgical excision. H. Secondary prevention for recipients should include close follow-up by a dermatologist (at least every 6 months), the use of topical retinoids to control actinic keratoses and to diminish squamous-cell carcinoma recurrence, and reduction of immunosuppression whenever possible. I. In recipients with multiple and/or recurrent skin cancers, the use of systemic retinoids, such as low-dose acitretin, could be recommended for months/years, if well tolerated, in addition to further reduction in immunosuppression whenever possible.

Humans↗
PubMed2001

[Progress in transplantation surgery--current status: kidney transplantation, recurrence of the primary illness and kidney transplantation].

Although there are numerous reasons for organ loss following transplantation, the recurrence of underlying disease plays a major role. Focal segmental glomerulosclerosis and mesangioproliferative glomerulonephritis are leading causes. Especially in children, hemolytic uremic syndrome (HUS) is a wide concern. If recurrence occurs, there is a high chance of graft loss within the next one to two years. Therapeutic options are minimal and focus on symptomatic relief of the ongoing vascular processes. Only metabolic causes may be treated by a combined transplantation, e.g., kidney plus liver in oxalosis and kidney plus pancreas in diabetes mellitus. Prospective therapeutic studies are required to solve part of the problem.

Humans↗
PubMed1992

The collaborative corneal transplantation studies (CCTS). Effectiveness of histocompatibility matching in high-risk corneal transplantation. The Collaborative Corneal Transplantation Studies Research Group.

The Collaborative Corneal Transplantation Studies (CCTS) were designed to evaluate the effect of donor-recipient histocompatibility matching and crossmatching on the survival of corneal transplants in high-risk patients. Corneas were allocated to the 419 patients in the double-masked Antigen Matching Study on the basis of serologically defined HLA-A, -B and HLA-DR antigen match. ABO blood group compatibility was determined but not used for recipient selection. The 37 patients in the Crossmatch Study were randomly assigned to receive a cornea from either a positively or negatively crossmatched donor. All patients received topical steroid therapy according to a standard protocol. Matching for HLA-A, -B and HLA-DR antigens had no effect on overall graft survival, the incidence of irreversible rejection, or the incidence of rejection episodes. At 3 years after surgery, the estimated proportion of eyes with graft failure was 41% for the ABO-incompatible group and 31% for the ABO-compatible group (relative risk, 1.43; 95% confidence interval, 1.00 to 2.06). The estimated proportion of eyes with failure from rejection by 3 years was 30% for the ABO-incompatible group and 16% for the ABO-compatible group (relative risk, 1.98; 95% confidence interval, 1.25 to 3.13). The positive group in the Crossmatch Study had fewer graft failures, rejection failures, and rejection episodes than the negative group; however, these differences were not statistically significant. These studies demonstrate that, for high-risk patients who are immunosuppressed by topical steroid therapy and followed up according to the CCTS protocol: (1) neither HLA-A, -B nor HLA-DR antigen matching substantially reduces the likelihood of corneal graft failure; (2) a positive donor-recipient crossmatch does not dramatically increase the risk of corneal graft failure; and (3) ABO blood group matching, which can be achieved with relatively little effort and expense, may be effective in reducing the risk of graft failure.

ABO Blood-Group System↗
PubMed1988

[Transplantation of a donor liver to 2 recipients (splitting transplantation)--a new method in the further development of segmental liver transplantation].

A donor liver was divided in such a way that the left part (segment II and III without caval vein) could be transplanted into a child, the right part (segment I, IV, V to VIII) into an adult successfully. Common bile duct and common hepatic artery remained with the left part of the liver, portal vein with the right one. In the recipient of the left part of the liver the own caval vein was preserved and anastomosed with the left hepatic vein; the other anastomoses were carried out in the typical way. In the recipient of the right part of the liver the right hepatic artery of the graft was anastomosed with the recipient's common hepatic artery using a saphenous interponate. Two separate intrahepatic bile ducts were anastomosed with a Roux-en-Y loop of the jejunum. The other anastomoses were carried out in the typical way. Thus the possibility of using one donor liver for two recipients (splitting transplantation) has been demonstrated.

Biliary Atresia↗