Experience with cyclosporine in 1519 kidney transplantations from living donors in a national transplant programme, 1983-2002.

Following the introduction of cyclosporine as basic immunosuppression in our national transplant programme in 1983, the pool of grafts from living donors (LDs) was expanded 2 years later by also accepting LDs mismatched for 2 HLA haplotypes and living unrelated donors (LURDs), mostly spouses. A policy of approaching family members to promote donation was consistently pursued. During 1983 through 2002, nephrectomy was performed on 1519 LDs without mortality.

Fewer relapses and increased chronic GVHD in patients transplanted with blood stem cells: a 5-year follow-up in a single centre study.

A total of 61 consecutive adult patients with haematological malignancies with an HLA-identical or one antigen-mismatched haploidentical family donor were randomised to allogeneic transplantation with blood stem cells (BSC) or bone marrow (BM). The median observation time was 5 years. Apart from engraftment parameters and acute graft-versus-host disease (GVHD), transplant-related mortality (TRM), incidence and severity of chronic GVHD, relapse, leukaemia-free survival (LFS) and overall survival (OS) were recorded.

Individualized T cell monitored administration of ATG versus OKT3 in steroid-resistant kidney graft rejection.

Acute steroid-resistant rejection episodes are recommended to be treated with set doses of anti-thymocyte globulin (ATG) or anti-CD3 monoclonal antibody (OKT3). Individualized T cell monitoring has been proposed as a tool for dose finding. A randomized study comparing the efficacy and safety of ATG (n = 27) with OKT3 (n = 28) in the treatment of biopsy verified acute steroid-resistant rejection (ASRR) when both drugs were administered on the basis of daily individualized T cell measurements.

Donation of stem cells from blood or bone marrow: results of a randomised study of safety and complaints.

Biological consequences and physical complaints were compared for donors randomly assigned either to blood stem cell (BSC) or bone marrow (BM) donation. In the period 1994-1999, 61 consecutive donors were included. The BSC donors were given G-CSF 10 microg/kg s.

A randomised study of allogeneic transplantation with stem cells from blood or bone marrow.

Sixty-one consecutive adult patients with leukaemia, primary myelofibrosis or myelodysplastic syndrome with an HLA-identical or one antigen mismatched family donor were randomised to allogeneic transplantation with PBPC or BM. Progenitor cells were mobilised into the blood by giving the donors 10 microg/kg/day G-CSF subcutaneously for 5-7 days. G-CSF was not given to patients after transplantation.

[Immunosuppressive agents in organ transplantation].

Initial use of intensive immunosuppressive therapy is mandatory after organ transplantation; during the following months treatment is tapered to the lowest effective and tolerable maintenance level. Immunosuppressants with different mechanisms of action are combined in order to obtain additive or synergistic effects, and to reduce the incidence of adverse effects. Traditional immunosuppressive agents like azathioprine, steroids, cyclosporine and polyclonal and monoclonal antibodies against T-cell antigens are challenged by new drugs like mycophenolate mofetil, tacrolimus, sirolimus and interleukin-2 receptor monoclonal antibodies.

The national kidney transplant program in Norway still results in unchanged waiting lists.

1. Of 2,670 patients starting renal replacement therapy for end-stage renal disease in Norway from 1989-1997, 76% were candidates for transplantation. The annual need for transplantations increased from 47 to 64 grafts PMP as the number of elderly patients increased.

Unrelated living donors in 141 kidney transplantations: a one-center study.

Background: Kidney transplantation is the optimal treatment for the majority of patients with end-stage renal disease. However, the shortage of kidneys for transplantation is a global problem, and any attempt to improve the donor situation would be of benefit to the growing number of patients on transplant waiting lists.

Patients And Methods: Since 1984, we have transplanted 141 kidneys from genetically unrelated living donors.

No prevention of cytomegalovirus infection by anti-cytomegalovirus hyperimmune globulin in seronegative bone marrow transplant recipients. The Nordic BMT Group.

A randomized multicentre study was conducted to evaluate the effect of anti-CMV hyperimmune globulin in the prophylaxis of CMV infections in CMV seronegative allogeneic BMT patients who received a transplant from a seropositive donor or who had received blood products unscreened for CMV during the treatment before BMT. Twenty-eight patients were included in the study. Thirteen were randomized to receive and 15 not to receive intravenous CMV hyperimmune globulin.

[Mycophenolate mofetil--a new immunosuppressive agent].

Mycophenolate mofetil is a prodrug that is rapidly converted to the active immunosuppressant mycophenolic acid. This substance inhibits the enzyme inosine monophosphate dehydrogenase, leading to a depletion of (deoxy-)guanosine nucleotides and thereby a reduction of de novo purine synthesis. Lymphocytes are relatively dependent on this pathway, particularly for RNA and DNA synthesis, and are thereby more susceptible to the antiproliferative effects of mycophenolate.

Pharmacokinetics and immunodynamics of chimeric IL-2 receptor monoclonal antibody SDZ CHI 621 in renal allograft recipients.

SDZ CHI 621 is a murine-human chimeric monoclonal antibody (mAb) to the interleukin-2 (IL-2) receptor (CD25) intended for prophylactic immunosuppression against acute rejection in the first several weeks following kidney transplantation. A multicentre, prospective, dose-finding study was conducted in 37 primary, mismatched cadaver kidney transplant patients to assess its tolerability, pharmacokinetics and immunodynamics. Successive cohorts of patients were stratified to receive total doses of 20, 30, 40 or 60 mg (n = 4, 4, 14, 15, respectively) administered as 15- or 20-mg intravenous infusions with the first dose given preoperatively and subsequent doses within the first 10 days posttransplant.

Ischemic heart disease--major cause of death and graft loss after renal transplantation in Scandinavia.

Causes of graft loss and death were studied in 1347 recipients of primary renal transplants followed for 5 years after transplantation irrespective of graft function. Immunosuppression consisted of high or medium dose CsA and prednisolone or low dose CsA and prednisolone and azathioprine. In recipients of cadaver grafts, death with a functioning transplant was more common than graft rejection after the first posttransplant year, accounting for 49% and 41% of the graft losses, respectively.

Pretransplant plasma exchange or immunoadsorption facilitates renal transplantation in immunized patients.

Patients with preformed antibodies against HLA molecules accumulate on renal transplant waiting lists and have inferior graft survival compared with nonsensitized patients. One hundred patients were included in a program of pretransplant removal of antibodies by plasma exchange (n = 90) or immunoadsorption (n = 10) in addition to prednisolone and cyclophosphamide medication. After plasma exchange, the panel reactivity and the antibody titer were reduced in about half of the patients, and after immunoadsorption the panel reactivity fell in 6 of 10 patients.

[Allogeneic transplantation of stem cells--procedure and biological aspects].

The biological challenges to be overcome for allogeneic stem cell transplantation to succeed include: 1, eradication of the patient's malignant tissue by effective, yet tolerable cytoreductive preconditioning; 2, suppression of the patient's immunocompetence to prevent graft rejection; 3, a stem cell graft of adequate haematopoietic capacity must be obtained from a donor of acceptable histocompatibility, and transferred to the patient; and 4, since the graft also contains lymphocytes mediating antirecipient donor alloimmunity, posttransplant immunosuppressive therapy is required to prevent, and sometimes to treat graft-versus-host disease. Basic immunobiological and clinical aspects, and methods used in stem cell transplantation are reviewed in the article.

HLA-A incompatibility associated with enhanced long-term renal graft survival in HLA-B, DR mismatched transplants.

The effect of HLA-A matching on long-term cadaver kidney graft survival was analysed, on average, 6 years after transplantation in a total of 1085 cyclosporine (CyA)-treated patients. A beneficial effect of HLA-A mismatching on graft survival was found by univariate and multivariate analyses (P < 0.05).

A randomized multicenter trial of cyclosporin and prednisolone versus cyclosporin, azathioprine, and prednisolone following primary living donor renal transplantation.

A total of 195 consecutive recipients of primary living donor renal transplants were randomized to receive either cyclosporin (CyA) and prednisolone (double therapy) or CyA, prednisolone, and azathioprine (triple therapy). There was no significant difference in patient or graft survival, incidence of acute rejection episodes, or major complications between the groups. The graft survival at 5 years was 71.