Compatible Grafts Research Articles

Is the ABO incompatibility a risk factor in bone marrow transplantation?

ABO histo -bloodgroups are strong transplantation antigens. In bone marrow transplantation, foreign ABO red cell antigens are not ignored by the immune system of the host, neither by the immunocompetent cells of the graft. Although ABO incompatibility is not considered a contraindication in bone marrow transplantation (BMT), its clinical consequences are still a matter of investigation. An overview of reports published by different groups is given and discussed. They present conflicting data regarding the role of the ABO match between patient and donor in the haematopoietic stem cell (HSC) transplantation. We report on the clinical outcome of bone marrow transplantation in 223 patients who received grafts from MHC identical siblings. Included are 139 ABO identical, 32 ABO minor mismatched, 34 major mismatched and 13 bi-directionally mismatched pairs. The statistical evaluation of standard parameters used to monitor the post -transplant period gave a proof that in neither group of patients with an ABO incompatible donor the recovery and success rate of transplantation, including the relapse incidence, risk of graft vs. host disease (GVHD) or overall survival, were significantly inferior. However, in all three cohorts of ABO mismatched patients, a delayed recovery of neutrophils was recorded as compared to the group receiving an ABO compatible graft. These finding leads us to the conclusion that the ABO compatibility is not a disadvantage in BMT, whereas the delayed recovery of neutrophils in patients having received an ABO mismatched graft is probably reflecting a transient humoral process leading to immune tolerance and graft accommodation.

Transient anti rhesus alloantibody produced by graft after non-myeloablative allogeneic stem cell transplant

Background: We report the case of a patient who received an allogeneic transplant with peripheral blood compatible ABO, Rhesus mismatched progenitor cells and who developed an asymptomatic transient anti Rhesus alloimmunisation. Case report: A 56-year-old man with renal cell carcinoma received a non-myeloablative allogeneic PBPC ABO compatible graft from his HLA-identical brother. Graft-versus-host disease prophylaxis consisted of cyclosporine alone. On day + 59, prior to any transfusion, a positive direct antiglobulin test (IgG++, C3d−) was detected. The indirect antiglobulin test (IAT) was considered doubtful, and IAT identification revealed the presence of an active anti Rhesus antibody (anti D specificity) in the patient’s serum. This immunisation had no clinical consequence, with no acute hemolytic episode. Further monitoring showed negative antibody screening tests on day + 78. Conclusion: To our knowledge this is the first reported case of transient anti Rh (D) allo-immunisation after non-myeloablative allogeneic peripheral blood progenitor cell (PBPC) transplant. The period of occurrence and the specificity of this antibody strongly suggest a donor cell origin.

Depletion of donor-reactive cells as a new concept for improvement of mismatched bone marrow engraftment using reduced-intensity conditioning

New nonmyeloablative strategies to improve acceptance of mismatched bone marrow (BM) may compensate for the inadequate supply of compatible grafts. Recently we proposed to facilitate engraftment of mismatched BM by selective depletion of activated donor-reactive host cells with cyclophosphamide (CY). Here we have compared engraftment of allogeneic BM after depletion of antigen-activated host lymphocytes by CY, with BM engraftment following general immunosuppression by the same CY dose. Naive or mildly irradiated BALB/c mice were primed with C57BL/6 BM cells (day 0), treated with CY in order to deplete activated T cells (day 1), and transplanted with a second C57BL/6 BM inoculum (day 2) in order to achieve BM engraftment. Alternatively, mice received an equal dose of donor BM cells in a single injection one day after the same CY dose. Treated animals were repeatedly tested for persistence of donor cells in the blood. Depletion of alloantigen-primed lymphocytes by 200 mg/kg CY provided stable GVHD-free engraftment of allogeneic BM in nonirradiated mice, while immunosuppressive treatment with the same CY dose alone resulted in BM rejection. Low-dose irradiation before priming with donor BM allowed the tolerance-inducing CY dose to be reduced to 100 mg/kg. Alloantigen-primed lymphocyte depletion (APLD) by a reduced CY dose resulted in engraftment of donor BM after a significantly lower irradiation dose than treatment with irradiation and CY alone. Our results demonstrate that conditioning that focuses on APLD has a definite advantage over general immunosuppression with CY and radiation therapy.

Depletion of alloantigen-primed lymphocytes overcomes resistance to allogeneic bone marrow in mildly conditioned recipients

Objective: Successful implantation of allogeneic bone marrow (BM) cells after nonmyeloablative conditioning would allow to compensate for the inadequate supply of compatible grafts and to reduce mortality of graft-vs.-host disease (GVHD). Recently, we proposed to facilitate engraftment of mismatched BM by conditioning for alloantigen-primed lymphocyte depletion (APLD) with cyclophosphamide (CY). Here we summarize the experimental results obtained by this approach. Materials and methods: Naive or mildly irradiated BALB/c mice were primed with C57BL/6 BM cells (day 0), treated with CY (day 1) to deplete alloantigen-primed lymphocytes, and given a second C57BL/6 BM transplant (day 2) for engraftment. Recipients were repeatedly tested for chimerism in the blood and followed for GVHD and survival. The protocol was also tested for inducing tolerance to donor tissue and organ allografts, and for treatment of leukemia, breast cancer, and autoimmune diabetes in NOD mice. Results: APLD by 200 mg/kg CY provided engraftment of allogeneic BM from the same donor in 100% mildly irradiated recipients. Eighty percent chimeras remained GVHD-free more 200 days. All chimeras accepted permanently donor skin grafts and donor hematopoietic stromal progenitors. Allogeneic BM transplantation (BMT) after APLD had a strong therapeutic potential in BALB/c mice harboring malignant cells and in autoimmune NOD recipients. Tolerance-inducing CY dose could be reduced to 100 mg/kg. Conditioning for APLD resulted in engraftment of allogeneic BM after a significantly lower radiation dose than treatment with radiation and CY alone. Conclusion: Our results demonstrate that conditioning for APLD has a definite advantage over general immunosuppression with CY and radiation therapy.

A novel extracorporeal kidney perfusion system: a concept model

The number of patients awaiting kidney transplantation has more than doubled in the past decade while the number of available donor organs has seen only a modest increase, leading to a critical shortage of organs. In response to this extreme shortage, the criteria for accepting organs have been modified to include marginal donors such as non-heart beating donors (NHBD). In these kidneys, determining viability is important for success of transplantation. Therefore, a study was undertaken to develop a system that would allow the extracorporeal assessment of function and compatibility of the donor organ before the patient is exposed to the risks associated with surgery. Following bilateral nephrectomy, the kidneys of 10 pigs (approximately 30 kg) were connected to a commercially available hypothermic pulsatile kidney perfusion apparatus. This system was modified to allow for normothermic pulsatile renal perfusion using the potential recipient's blood, via vascular access. These kidneys were perfused with the animal's blood for a minimum of two hours while various parameters were monitored. Perfusion pressures were kept between 60 and 90 mmHg, which correlated to flows between 70 and 150 mL/min. A decrease in perfusion pressure with a concomitant rise in flow over the two-hour period served as a good predictor of a viable and compatible graft. The modified kidney preservation system allows the normothermic, pulsatile extracorporeal perfusion of donor kidneys with the ability to monitor resistance to flow and urine production. This model also allows observation of the kidney for signs of hyperacute rejection. Further research needs to be conducted in order to determine if the system represents a methodology to increase the pool of available donor organs.

Embriões, células-tronco e terapias celulares: questões filosóficas e antropológicas

AS THE possibility of therapeutic cloning in humans has just been demonstrated by a Corean group of researchers, the paper argues that biotechnologies of that kind may contribute to alleviate the chronic shortage of organs and tissues for transplantation. Ever since immunosuppressant drugs have become available, transplantation surgery has made considerable progress, and the procurement of transplants, especially from living donors, has been problematic. The investigation of the properties of (adult or embryonic) stem cells opened great hopes. Conditions such as diabetes, multiple sclerosis, myocardial infarct, or neurodegenerative diseases (Parkinson's, Alzheimer's, Huntington's diseases), could be treated by cellular therapy, namely, transplantation of human cells issued from cell lines derived from human stem cells possibly stored in cell banks. Adult stem cells, however, are rare and difficult to identify (apart from bone marrow, which contains the precursors of blood cells, a resource already widely used). There exists a large supply of human embryonic stem cells in countries where the freezing of embryos for the purposes of medically assisted procreation leaves 'spare' or 'surplus' embryos which may be either destroyed or donated for research after couples have fulfilled their procreative aim. It is often considered that harvesting stem cells from those embryos, for use in research or therapeutics, is morally more acceptable than destroying them. But the constitution of stem cell banks is open to two objections. First, in order to offer HLA compatible grafts to a large population, the bank should offer a selection of cell supplies representative of all HLA types in the population, a virtually impossible task. Second, with HLA compatible grafts there remains a risk of immunorejection, and a necessity for the patients treated to take immunosuppressant drugs for the rest of their lives. Should biological research establish their feasibility and safety, cloning techniques might then appear to be the best choice. Treating (for example) diabetic patients with cells constructed by transferring the nucleus of a somatic cell of the patient into an enucleated oocyte would have the double advantage that the graft would be immunocompatible with the receiver, and that cell banks would not be required; instrumentalizing women for the collection of oocytes has been found objectionable, but a Chinese group of researchers suggested the possibility of using animal oocytes. It remains that such practices have raised lots of ethical controversies. It is at this moment difficult to assess their impact on our vision of 'humanity'.

LIVER TRANSPLANTATION FOR FULMINANT HEPATIC FAILURE: EXPERIENCE WITH 40 ADULT PATIENTS OVER A 17 YEAR PERIOD

P577 Aims: The overall prognosis for patients with FHF is quite poor without transplantation, with survival rates usually reported between 10% and 30% in relation with the type of clinical presentation. Aim of this study is to evaluate the influence of pretransplant recipient and donor prognostic factors on graft-patient survival. Methods: From April 1986 to June 2003, 796 LT were performed in 696 patients. In the same period, 40 (5,7%) adult patients underwent to first liver transplantation for FHF. The mean age was 32 years (range 17-60); 45% of recipients were male and 55% were female. The coma’s grade was defined by Glasgow Coma Score (GCS) scale. Among the pretransplant recipients variables we analyzed: age, gender, type of FHF, aetiology, time list to LT, Glasgow Coma Score, prothrombin time, AST, ALT, total bilirubin, serum-creatinine, era of transplant, packed red blood cells (PRBC), ischemic period, total operation time, type of surgical procedure (with or without veno-venous by-pass). The following pretransplant donor variables were analyzed too: age, gender, cause of death, ICU stay, ABO match, type of perfusion solution. We used preoperative supportive therapies as bridge to LT by a Bio Artificial Liver (BAL) with porcine cells in one case and by Extra Corporeal Artificial Device with human hepatocytes in another one. The mean patient follow-up time was 41.6 months (range 0-178 months). Results: The indication for transplantation was hyperacute-FHF in 25 cases (62.5%), acute-FHF in 14 (35%), and subacute hepatic failure in one (2.5%). In 52,5%, the aetiology of FHF was virus B infection (21 patients). The other indications were: Amanita Phalloides intoxication in 5 cases, Wilson’s disease in 2, Budd-Chiari Syndrome in one and paracetamol intoxication in another one, in 10 cases (25%) the origin remained unknown. Pre-transplant GCS was <5 in 22 patients (55%) and ≥5 in 18 patients (45%). By far the majority of patients (24/40; 60%) the waiting list time was <48h, while in the remaining 16 patients (40%) it was ≥48h. An identical or compatible graft was used in 87,5% of recipients, while in 12,5% (5/40) a incompatible graft was transplanted. The overall graft survival was 48.3%, 41.1% and 41.1% at 1, 3 and 5 years, respectively, whereas patient survival was 61.3%, 54.6% and 50.4% at 1, 3 and 5 years, respectively. None of the donor parameters analyzed had a significant impact on graft and patient survival. The only recipient variable which had a statistically significant impact on graft survival resulted the waiting list to transplant <48 hours (p=0.05). The overall patient survival resulted slightly influenced by the mean AST level > 1043 U/l, as well as by the mean total operation time >533 minutes. In the incompatible group 4 out of 5 patients lost the graft for acute rejection (3 cases) and PNF (1 case). Conclusions: Liver transplantation remains the better treatment for fulminant hepatic failure. Based on our results the prognostic factors influencing the graft survival is represented by short waiting list time to LT less than 48 hours. Further studies are need to validate extracorporeal support system with either porcine liver cells or non utilized human hepatocytes as a bridge to transplantation.

THE EFFECT OF HLA MISMATCHES, SHARED CREGS, AND SHARED HLA-DR ON THE OUTCOME AFTER PEDIATRIC LIVER TRANSPLANTATION

O96* Aims: Prospective HLA matching is not routinely performed before liver transplantation. However, on the basis of experimental studies, reconsideration of these procedures may be justified, especially in pediatric recipients. The aim of this study was to analyse the effect of the number of HLA mismatches, the number of shared common cross-reactive antigen groups (CREGs), and the number of shared HLA-DR antigens on the outcome after liver transplantation in an exclusively pediatric population. Methods: Inclusion criteria were primary transplants with an ABO-identical or compatible graft with an immunosuppressive regimen consisting of cyclosporine or tacrolimus. All transplants should have had a possible follow-up of at least one year. In this way, 136 consecutive transplants could be analysed. Outcome parameters were graft survival, acute rejection within three months, and portal fibrosis at one year after transplantation. A subgroup analysis was made considering full-size (FS) and technical-variant (TV) liver grafts. The influence of HLA mismatches, shared CREGs, and shared HLA-DR antigens on the outcome was assessed by using adjusted multivariate analysis. Confounding factors related to recipients, donors, transplant procedures (including immunosuppression), and postoperative complications were identified. Results: HLA mismatching, shared CREGs, and shared HLA-DR did not influence overall graft survival, nor survival of FS liver grafts. Survival of TV grafts was better in case of two mismatches at the HLA-DR locus compared to zero or one mismatch at this locus (P=0.01) and better in case of none shared HLA-DR antigens compared to one shared HLA-DR antigen (P=0.004). Of 86 one-year posttransplant biopsies, 33 (38%) showed normal histology and 29 (34%) showed portal fibrosis. The remaining 24 (28%) biopsies were excluded because of other histopathologic abnormalities. The incidence of portal fibrosis in grafts with zero or one mismatch at the HLA-DR locus was 59% compared to 36% with two mismatches at this locus (P=0.08). The incidence of portal fibrosis after FS transplantation was 34% and after TV transplantation 60% (P=0.04). Analyzing the effect of HLA-DR mismatches on the incidence of portal fibrosis considering graft type, revealed 9 of 9 (100%) TV grafts with 0-1 mismatches at the HLA-DR locus showing portal fibrosis compared to 9 of 21 (43%) grafts with 2 mismatches (p=0.004). After adjusted multivariate regression analysis, matching for HLA-DR (β=0.19, 95%CI 0.05–0.75, P=0.02) as well as TV liver grafts (β=6.26, 95%CI 1.49–23.20, P=0.01) proved to be independent risk factors for portal fibrosis. HLA did not influence the incidence of acute rejection. Conclusions: HLA-DR mismatching had a positive effect on survival of technical-variant liver grafts and was associated with a lower incidence of portal fibrosis in such grafts. Shared HLA-DR antigens had a negative influence on survival of technical-variant grafts.

Hepatic allograft arterialization by means of the gastroduodenal bifurcation (branch patch) as a prognostic factor.

Because of the current shortage of cadaveric organs, it is important to determine preoperatively those variables that are readily available, inexpensive, and noninvasive that can predict a higher incidence of hepatic artery thrombosis (HAT). From April 1986 to October 2001, 717 patients underwent 804 liver transplants. All the arterial reconstructions were performed with fine (7-0) monofilament sutures in an interrupted fashion. Two methods were used: group I, end-to-end arterial anastomosis, and group II, the gastroduodenal branch patch. After a mean follow-up of 72 (range 3-174) months, HAT was observed in 19 patients (overall incidence 2.4%). End-to-end anastomosis (group I) was performed in 39.50% (316) of cases, and HAT developed in 14 (4.4%) cases. Branch-patch anastomoses (group II) were carried out in 60.5% (488) of the patients; the presence of HAT was detected in five cases (1.03%) (P = 0.03, P < 0.05). A total of 21 variables were selected in the univariate analysis; however, after the multivariate analysis, all but two of the factors lost statistical significance, and these corresponded to the type of arterial reconstruction (gastroduodenal branch patch vs. end-to-end) and the ABO compatibility. Liver transplantation with compatible grafts using branch-patch anastomosis for the arterialization (both manipulative by the transplant team) reduces HAT-derived loss of grafts, with the consequent increase in graft availability and reduced mortality rate on the waiting list.

Liver transplantation across ABO blood groups in children

Late results after ABOI LTx are inferior to ABO compatible organs. We report seven patients who received LTx across ABO group for emergency indications. The blood type combinations were: A to O in three, B to O in two, and B to A in two. Episodes of acute and chronic rejection, immunosuppression, and biochemical and functional tests after transplantation as well as patient and graft survival were compared between ABOI group and patients with compatible ABO group transplanted due to FLF (group I) or in an elective setting (group II). Four children are alive. Two children died of sepsis and CNS damage or MOF, and one patient died during transplantation because of cardiac failure. All recipients of ABOI grafts received immunosuppression with cyclosporine or tacrolimus and steroids. MMF was added in two subjects, and induction with antilymphocyte globulins used in five patients. An acute rejection episode was diagnosed in two recipients between 7 and 11 days after LTx. All four living patients with ABOI grafts are doing well with follow-up time between 11 months and 5 years. In one patient PTLD occurred at 1 year after ABOI LTx but was cured by discontinuation of immunosuppression and administration of rituximab. Graft survival in the ABOI group was 57.1% versus 71% in group I and 73% in group II. Respective patients survival was 57.1% 71%, and 82.0% respectively. In conclusion, in urgent cases ABOI transplantation is justified in pediatric patients when compatible grafts are not available.

New Prostheses for Use in Bypass Grafts with Special Emphasis on Polyurethanes

Vascular bypass procedures using traditional prosthetic grafts such as polytetrafluoroethylen (PTFE) and polyethylene tetraphthlate (Dacron) are prone to failure when used in low flow states such as in below knee bypass and when the diameter of the graft is less than 6 mm. A major factor in this is compliance mismatch between the graft and the diseased vessel, which may cause intimal hyperplasia at the distal anastomosis. PTFE and Dacron are rigid grafts with poor compliance. By improving the compliance of the prosthetic graft it is hoped that patency will improve. Recent advances in polyurethane chemistry have developed materials that do not degrade and which allow compliance matching of the graft to the patient's vasculature. It is now possible to manufacture biologically and haemodynamically compatible grafts with small diameter from these polyurethane graft materials. This review will focus on the lack of compliance in current vascular bypass grafts and the promise of the new polyurethane polymers in a new generation of small-bore bypass grafts.

Predicting time on the waiting list for HLA matched corneal grafts.

Recent studies report the beneficial effect of HLA matching for the long-term prognosis of penetrating keratoplasty (KP). This improvement in prognosis, however, has to be weighed against the additional waiting time while a HLA compatible graft is found. Precise estimation of this additional waiting period is a prerequisite for informed consent on the waiting policy. A mathematical model based on survival analysis and HLA haplotype frequencies was used to estimate time on the waiting list for each of 1400 HLA typed patients registered at the Lions Cornea Bank North Rhine Westfalia (NRW). Additionally, the waiting period for each patient was retrospectively determined. Both values were tested for correlation. This analysis was performed for acceptance of up to two mismatches on HLA-A, -B and -DR. The median predicted waiting period was compatible with the median waiting period in retrospective simulation. Correlation of both entities was statistically significant also. Predicted time on the waiting list as derived from the patient's HLA genotype and a comprehensive database of HLA haplotype frequencies is thus a valuable tool for management of HLA-matching in KP.

Peroxidase Isozyme Profiles in Compatible and Incompatible Pear-Quince Graft Combinations

The similarity or differences of peroxidase isozymes in rootstocks and scions may influence their graft compatibility. This study was conducted to identify peroxidase isozymes that may be used as markers to predict compatibility between pear (Pyrus communis L.) and various quince (Cydonia oblonga Mill.) clones. `Bartlett' (BT) and `Beurre Hardy' (BH) pear cultivars are known to form incompatible and compatible grafts, respectively, with quince rootstocks. The two pear scion cultivars were budded on `quince A' (QA), `quince BA-29', and 15 selected quince clones from Turkey. Bark and cambial tissues were taken from nonbudded rootstocks and scions, and 4 cm above and below the graft union for peroxidase isozyme analysis performed by starch gel electrophoresis. Isoperoxidase analyses were also performed on samples from the graft unions collected 12 months after grafting. Many isozyme bands were observed commonly in the two scions; however, one anodal peroxidase A was detected in BH (compatible scion) but not in BT (incompatible scion) samples. This isoperoxidase was also detected in QA, Quince BA-29, and nine of the Turkish quince clones. Another isoperoxidase, band B, was detected in BH but not in BT or any of the rootstocks. However, the compatible (BH/QA) and moderately compatible (BT/BA-29) graft union tissues contained bands A and B whereas incompatible graft union tissues (BT/QA) lacked both. Graft union samples involving BT and five Turkish quince clones (705, 609-2, 702, 804, and 806) had both `A' and `B' isoperoxidases while one or both of these bands were absent in nonbudded graft partners. Field observations of 3.5 year-old grafts of BT and Turkish quince clones revealed that the vegetative growth (vigor) of BT scion was significantly greater, when grafted on these five clones, than that in graft combinations with other clones. We suggest that matching of isoperoxidase `A' in quince rootstocks and BH pear scion may be associated with a compatible graft combination. Additionally, presence of isoperoxidases `A' and `B' in the graft union tissues may be used as an indicator to predict a compatible graft between BT and quince rootstocks.

New prostheses for use in bypass grafts with special emphasis on polyurethanes

Vascular bypass procedures using traditional prosthetic grafts such as polytetrafluoroethylen (PTFE) and polyethylene tetraphthlate (Dacron) are prone to failure when used in low flow states such as in below knee bypass and when the diameter of the graft is less than 6 mm. A major factor in this is compliance mismatch between the graft and the diseased vessel, which may cause intimal hyperplasia at the distal anastomosis. PTFE and Dacron are rigid grafts with poor compliance. By improving the compliance of the prosthetic graft it is hoped that patency will improve. Recent advances in polyurethane chemistry have developed materials that do not degrade and which allow compliance matching of the graft to the patient's vasculature. It is now possible to manufacture biologically and haemodynamically compatible grafts with small diameter from these polyurethane graft materials. This review will focus on the lack of compliance in current vascular bypass grafts and the promise of the new polyurethane polymers in a new generation of small-bore bypass grafts.

Improving vascular grafts: the importance of mechanical and haemodynamic properties.

In the last 40 years, as techniques and materials have improved, the success rate of vascular prostheses with a diameter greater than 6mm has risen steadily, 5-year survival rates exceeding 95% in most centres. With smaller grafts no comparable improvement has occurred, the majority failing within 5 years, usually as a result of intimal hyperplasia and, ultimately atherosclerosis, in and around the downstream anastomosis. Clinical evidence suggests that the patency rates of small grafts are improved by matching the elastic properties of the graft to that of the artery into which it is placed. Although there is little reliable evidence that 'elastic mismatch' per se is the cause of intimal hyperplasia, it is generally accepted that mechanical factors are important in its genesis. These include disturbed flow at the anastomosis leading to fluctuations in shear stress at the endothelium (a known cause of intimal hyperplasia in normal arteries), injury due to suturing and stress concentration at the anastomosis. Few suitable materials or techniques have yet been developed to improve the long-term survival rates of small grafts. Recent advances in tissue engineering in which prostheses are manufactured by culturing vascular smooth muscle cells on a tubular scaffold of biodegradable polymer may ultimately make it possible to manufacture biologically and haemodynamically compatible grafts with diameters as small as 1mm.

Long-term immunosuppression without corticosteroids after orthotopic liver transplantation: A positive therapeutic aim

Long-term treatment with corticosteroids after orthotopic liver transplantation (OLT) may cause adverse effects, particularly hypertension, diabetes, and bone disease. The results of steroid withdrawal from long-term immunosuppression in 114 patients after OLT was reviewed. Initial treatment was with corticosteroids, azathioprine, and cyclosporine A in 76.3% and with antithymocyte globulin in 17.5%. Corticosteroids were stopped in 96 patients (84.2%) during mean follow-up of 6.7 +/- 3.9 months, and acute rejection subsequently developed in 8. By comparison 7 of 18 patients, in whom corticosteroids were continued, developed acute rejection. Six of these had received blood group (ABO)-compatible nonidentical grafts. Rates for retransplantation in the steroid withdrawal and nonwithdrawal groups were 4.2% and 22.2%, respectively, and mortality in the two groups was 14.6% and 44.4%, respectively. Azathioprine was not given or withdrawn in 28 patients in the group from which corticosteroids were also withdrawn, with no adverse effect. Diabetes mellitus improved following corticosteroid withdrawal, but there was no improvement in hypertension. We conclude that corticosteroids can be safely withdrawn in the majority of patients after OLT.

ABO blood group incompatibility in liver transplantation: a single-centre experience.

For most organ transplantation (Tx), ABO blood group incompatibility (ABOI) is an absolute contraindication because of the high incidence of hyperacute rejection (HAR). While HAR occurs in ABOI liver Tx (LTx), it is known that some liver grafts can be accepted. ABO-incompatible (ABOI) liver allografts were used in seven of 355 orthotopic LTx operations performed at our institution over a 10-year period. All seven recipients were in fulminant hepatic failure (FHF) prior to Tx. Following Tx, all grafts functioned immediately. One patient died without recovering consciousness. Six patients recovered consciousness following Tx but three patients subsequently required re-transplantation (with ABO-compatible grafts (ABOC)) because of severe acute rejection (2) and chronic rejection (1). Hyper-acute rejection did not occur. All six patients are now well, with a mean survival of 61.5 months. When compared to 36 other FHF patients who received ABOC grafts, graft survivals were 3/7 (43%) for ABOI versus 23/36 (64%) for ABOC (P = not significant (NS)). Patient survivals were 6/7 (85.7%) for ABOI patients and 23/36 (64%) for ABOC (P = NS). The re-transplantation rate was significantly higher in the ABOI group (P = 0.001). The results confirm that ABOI liver grafts should be used in urgent circumstances when compatible grafts are not available. Some grafts function indefinitely, while those that fail may function for sufficient time to allow successful retransplantation with ABOC grafts.

The Possible Role of Phenolics in Incompatibility Expression in Eucalyptus gunniiMicrografts

As a result of incompatibility, Eucalyptus gunnii showed in the graft area of in vitro micrografts a typical accumulation of gallic, ellagic, gentisic and p-coumaric acid: (+)-catechin also increased in concentration. In compatible grafts, a lower concentration of phenolics accumulated. The possible role of both specific types of phenolic accumulation and the higher activities of soluble peroxidases and polyphenol oxidase in incompatible grafts as opposed to compatible ones is discussed.

The Possible Role of Phenolics in Incompatibility Expression in Eucalyptus gunnii Micrografts

As a result of incompatibility, Eucalyptus gunnii showed in the graft area of in vitro micrografts a typical accumulation of gallic, ellagic, gentisic and p-coumaric acid: (+)-catechin also increased in concentration. In compatible grafts, a lower concentration of phenolics accumulated. The possible role of both specific types of phenolic accumulation and the higher activities of soluble peroxidases and polyphenol oxidase in incompatible grafts as opposed to compatible ones is discussed.

Selection of the most compatible graft recipient by computer program, used in regional tissue typing laboratory of Hellas (R.T.T.L.).

The purpose of this study was to present the new computer program that we developed in the regional tissue typing laboratory (R.T.T.L.) and use for the selection of the most suitable recipient for cadaveric allografts in a more efficient way. This new program was written and compiled in TURBO PASCAL 6.0, sorts all possible recipients to the HLA type of a donor, checks for the existence of splits and utilises them, and when requested, gives out results to more specific inquiries, i.e. all compatible recipients from 2DR2B2A to 1DR0B0A matching. It can also forecast success percentages according to different factors, i.e. combination of donor's and recipient's ages, HLA matching etc. The material used for this study were the patients who are registered in the formal cadaveric transplantation list of R.T.T.L. We have used this program since 2 January 1992 together with the old one. Since then we found that the new program is faster in sorting all the possible recipients of cadaveric renal allografts according to the criteria already mentioned. The total selection time, with all the criteria activated, averages a few seconds, whereas with the old program it took approximately 2 min just for the sorting of HLA matching, without any other criteria activated. In the printout of the final result of each inquiry are all the possible recipients in the sorted order together with relevant data (telephone number, address etc.). As a result, the laboratory personnel has been free from the tedious task of this sorting which was initially done by hand and the possibility of error has been eliminated. The program was developed exclusively by doctors and all the updates needed are done by the users. More important, however, is the fact that in many cases the time of cold ischaemia was reduced by more than 30 min with all the obvious advantages for the longevity of the graft's life.