Low-dose Maintenance Immunosuppression Research Articles

Outcomes with alemtuzumab induction therapy in lung transplantation: a comprehensive large-scale single-center analysis.

Alemtuzumab is a monoclonal antibody targeting CD52, increasingly used as induction therapy after transplantation. The aim of this study was to analyze the outcomes of alemtuzumab induction therapy followed by a low-dose maintenance immunosuppression in a large single-center cohort of lung transplant recipients. All patients, who received alemtuzumab induction followed by a low-dose maintenance immunosuppression were included in the analysis. Short- and long-term outcomes were analyzed. 721 lung transplant recipients, transplanted between January 2008 and June 2019, were included in this retrospective study. Freedom from higher-grade ACR at 1, 5, and 10years was 98%, 96%, and 96%, respectively. Thirty-nine patients (5%) developed clinical AMR. Twenty-one percent of patients developed high-grade CKD. A total of 1488 infections were recorded. Sixteen percent were diagnosed within the first 3months. Sixty-two patients (9%) developed a malignancy during follow-up. Freedom from CLAD at 1, 5, and 10years was 94%, 72%, and 53%, respectively. Overall survival rates at 1, 5, and 10years were 85%, 71%, and 61%, respectively. Alemtuzumab induction combined with a low-dose tacrolimus protocol is safe and associated with low rates of acute and chronic rejection, as well as an excellent long-term survival.

Continuous function of 80 primary renal allografts for 30-47 years with maintenance prednisone and azathioprine/mycophenolate mofetil therapy: A clinical mosaic of long-term successes.

Eighty primary renal allograft recipients, 61 living-related and 19 deceased donor, transplanted from 1963 through 1984 had continuous graft function for 30-47years. They were treated with three different early immunosuppression programs (1963-1970: thymectomy, splenectomy, high oral prednisone; 1971-1979: divided-dose intravenous methylprednisolone; and 1980-1984: antilymphocyte globulin) each with maintenance prednisone and azathioprine, and no calcineurin inhibitor. Long-term treatment often included the anti-platelet medication, dipyridamole. Although both recipient and donor ages were young (27.2±9.5 and 33.1±12.0years, respectively), six recipients with a parent donor had >40-year success. At 35years, death-censored graft survival was 85.3% and death with a functioning graft 84.2%; overall graft survival was 69.5% (Kaplan-Meier estimate). Biopsy-documented early acute cellular and highly probable antibody-mediated rejections were reversed with divided-dose intravenous methylprednisolone. Complications are detailed in an integrated timeline. Hypogammaglobulinemia identified after 20years doubled the infection rate. An association between a monoclonal gammopathy of undetermined significance and non-plasma-cell malignancies was identified. Twenty-seven azathioprine-treated patients tested after 37years had extremely low levels of T1/T2 B lymphocytes representing a "low immunosuppression state of allograft acceptance (LISAA)". The lifetime achievements of these patients following a single renal allograft and low-dose maintenance immunosuppression are remarkable. Their success evolved as a clinical mosaic.

Unusual presentation of mucormycosis

Early post-kidney transplant period is at high risk of acquiring fungal infections due to maximum immunosuppression. We are reporting case of a 39-year-old male who did well for 16 years after renal transplantation, and then had gastric mucormycosis mimicking acute pancreatitis while on low dose maintenance immunosuppression. At admission, his clinical and laboratory parameters were suggestive of the acute pancreatitis but further worsening needed invasive investigations. Endoscopy was done and histopathology of large irregular gastric ulcer with yellow base and raised margin and tissue staining confirmed the fungus. Subsequent treatment with combined fungal therapy of amphotericin and posaconazole did not save our patient. The case highlights that mucor can present late when on low dose immunosuppression and can mimic acute pancreatitis.

Adolescence: Challenges and responses

Adolescence: Challenges and responses

Lymphoproliferative Disorders After Solid Organ Transplantation—Classification, Incidence, Risk Factors, Early Detection and Treatment Options

Posttransplant lymphoproliferative disorder (PTLD) is a heterogeneous disease group of benign and malignant entities. The new World Health Organisation classification introduced in 2008 distinguishes early lesions, polymorphic, monomorphic and classical Hodgkin lymphoma-type PTLD. Based on the time of appearance, early and late forms can be identified.PTLDs are the second most frequent posttransplantation tumors in adulthood, and the most frequent ones in childhood. The incidence varies with the transplanted organ-from 1%-2% following kidney transplantation to as high as 10% following thoracic organ transplantation-due to different intensities in immunosuppression. Immunocompromised state and Epstein-Barr virus (EBV) infection are the two major risk factors.In Europe and the US approximately 85% of PTLDs are of B-cell origin, and the majority are EBV-associated. Symptoms are often unspecific; extranodal, organ manifestations and central nervous system involvement is common. Early lesions respond well to a decrease in immunosuppression. Malignant entities are treated with rituximab, chemotherapy, radiotherapy and surgical therapy. Adoptive T-cell transfer represents a promising therapeutic approach. The prognosis is favorable in early PTLD, and poor in late PTLD. Five-year survival is 30% for high-grade lymphomas. The prognosis of EBV-negative lymphomas is worse.Lowering the risk of PTLD may be achieved by low dose maintenance immunosuppression, immunosuppressive drugs inhibiting cell proliferation, and special immunotherapy (e.g. interleukin-2 inhibitors). Early detection is especially important for high risk-e.g. EBV-negative-patients, where the appearance of EBV-DNA and the increase in its titer may help.

396: Successful Outcomes in Human Lung Transplantation with Campath Induction and Low Dose Maintenance Immunosuppression

396: Successful Outcomes in Human Lung Transplantation with Campath Induction and Low Dose Maintenance Immunosuppression

A long-term study on hyperlipidemia in stable renal transplant recipients.

Hyperlipidemia is a common and important risk factor after renal transplantation, but there is little long-term data on its incidence, pattern, and evolution in stable renal allograft recipients on low dose maintenance immunosuppression. A retrospective study was conducted on all patients who received kidney transplants from April 1, 1990 to March 31, 2000 at a single center, on their serial lipid profile during the first 3 yr after kidney transplantation. A total of 221 (122 male, 99 female; mean age 37.8 +/- 10.0 yr at the time of transplantation) Chinese adult renal allograft recipients were included. A 95.3% of patients were on cyclosporine and prednisolone based immunosuppression. Increases in total cholesterol (TC), low density lipoprotein (LDL), and high density lipoprotein (HDL) were noted, while the level of triglyceride (TG) decreased after renal transplant. The incidence of hypercholesterolemia (defined as TC >/= 6.3 mmol/L or LDL >/= 4.2 mmol/L) within the first year was 28.2 and 20.3%, respectively. The incidence rate decreased significantly in the second (5.4%, p = 0.000 and 6.4%, p = 0.003) and third year (9.5%, p = 0.003 and 4.9%, p = 0.021), but the incidence of patients having a high risk-ratio (defined as TC/HDL >/= 5) remained unchanged (6.9, 4.9 and 10.3% within the first, second, and third year, respectively). Treatment with statin was necessitated in 6.8, 13.6 and 21.7% of the patients at 1, 2, and 3 yr after transplantation, respectively. The prevalence rates of elevated TC and LDL were 18.3 and 18.9% at baseline, 40.6 and 33.3% after 1 yr, 32.8 and 27.3% after 2 yr, and 24.8 and 19.0% after 3 yr, despite treatment. The prevalence of patients with a high risk-ratio was 45.0% at baseline, 30.5% after 1 yr (p = 0.002), 22.6% after 2 yr (p = 0.000) and 21.8% after 3 yr (p = 0.000). Hypercholesterolemia at the time of transplantation was an independent predictor for post-transplant hypercholesterolemia (odds ratio 3.76, 95% confidence interval 1.47-9.62, p = 0.006). Renal transplantation is associated with a characteristic pattern of dyslipidemia, with increased TC, LDL and HDL, and a decrease in TG. Patients with pre-existing hypercholesterolemia were at higher risk for post-transplant hypercholesterolemia. Although the incidence of hypercholesterolemia peaks within the first year after transplantation, this remains a long-term complication in a significant proportion of patients on low dose immunosuppressive medications.

Comprehensive examination of gene expression associated with long-term stable graft acceptance by renal transplant recipients.

Expression levels of mRNA in peripheral blood mononuclear cells from five renal transplant recipients and five non-transplanted controls were analyzed with GeneChips (GeneChip Instrument system, Affymetrix, Santa Clara, CA, USA). All recipients had retained a well-functioning kidney graft for more than 15 yr on low-dose maintenance immunosuppression. Among a total of 12630 transcripts examined, significant differential expression was observed for 599 genes, whereby 470 genes were up-regulated and 129 down-regulated in the transplant recipients compared with controls. Of these, 192 up-regulated and 46 down-regulated genes showing a change greater than twofold were divided into eight functional categories as follows (numbers of genes, up/down): immune system (12/14), cell proliferation (17/3), oncology (15/3), transporter/receptor/binding protein (16/5), transcription factors (8/2), enzymes (17/4), expressed sequence tags (91/9), and others (16/6). Predictably, expression of immune-associated genes was decreased in the recipients. Significant reduction of expression levels of CD3, ICAM-1, and B7.2, which are critical molecules for interactions between antigen presenting cells and T cells, were observed. In T cell signal transduction, the Ras pathway was likely to be suppressed by activation of hVH-5. The present data help to elucidate the immunological status in long-term kidney graft recipients and may provide insights for future regimens to establish donor-specific hyporesponsiveness.