Kidney transplant from the same donor without maintenance immunosuppression after previous hematopoietic stem cell transplant.

In January 2005, an 18-year-old male patient with acute myeloid leukemia (AML) received a haploidentical hematopoietic stem cell transplantation (HSCT) from his father. He developed hemolytic uremic syndrome and end-stage renal disease (ESRD) requiring hemodialysis on day 357 after HSCT. On day 1020 after HSCT, a living kidney donation from the stem cell donor was carried out. The creatinine before kidney transplantation (KT) was ≈450 µmol/L, 268 µmol/L on day 2 after KT, 88 µM on day 38 and 89 µmol/L on day 960 (day 1980 after HSCT). Immunosuppression was gradually discontinued: cortisone on day 28, tacrolimus on day 32 and MMF on day 100 after KT (day 1120 after HSCT). As of June 2010, 66 months after HSCT and 32 months after KT, the patient has had neither rejection episodes nor clinical manifestations of transplantation-related complications. The patient reached 100% hematopoietic donor chimerism prekidney transplant and retained this state postkidney transplant. This unique case is the first report of a successful kidney transplant without immunosuppression after HSCT from the same haploidentical donor.

Determination of rubella virus-specific cell-mediated immunity using IFN gamma-ELISpot.

Immunity to rubella virus (RV) is conventionally determined by measuring specific immunoglobulin G (IgG). However, several individuals may be considered immune despite undetectable antibody levels. In the present study RV-specific interferon-gamma (IFN gamma)-ELISpot and rubella-IgG-ELISA were compared in 75 young adults aged between 20 and 30 years. In a subgroup, not only rubella-like particles (RLP), but also HPV77 rubella vaccine derived antigen was used in IFN gamma-ELISpot. The results from both, ELISA and ELISpot were independent of previous encounter to RV (vaccination, exanthematous disease, or childhood infection). There was no difference between RLP and RV vaccine antigen in IFN gamma-ELISpot response, and there was no correlation between IFN gamma-ELISpot and RV-specific IgG levels. IFN gamma-producing cells were found in 78.7% of all tested persons, and 83.8% of them were positive in ELISA. In almost all individuals seronegative for RV antibody, IFN gamma-producing cells were detected. Considering both humoral and cell-mediated immune responses, a positive RV immune reaction was seen in 98.6%. The results indicate that the IFN gamma-ELISpot can provide valuable additional information in seronegative individuals.

A pharmacokinetic model of filgrastim and pegfilgrastim application in normal mice and those with cyclophosphamide-induced granulocytopaenia.

OBJECTIVES: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used as treatment for granulocytopaenia during cytotoxic chemotherapy; however, optimal scheduling of this pharmaceutical is unknown. Biomathematical models can help to pre-select optimal application schedules but precise pharmacokinetic properties of the pharmaceuticals are required at first. In this study, we have aimed to construct a pharmacokinetic model of G-CSF derivatives filgrastim and pegfilgrastim in mice. METHODS: Healthy CD-1 mice and those with cyclophosphamide-induced granulocytopaenia were studied after administration of filgrastim and pegfilgrastim in different dosing and timing schedules. Close meshed time series of granulocytes and G-CSF plasma concentrations were determined. An ordinary differential equations model of pharmacokinetics was constructed on the basis of known mechanisms of drug distribution and degradation. RESULTS: Predictions of the model fit well with all experimental data for both filgrastim and pegfilgrastim. We obtained a unique parameter setting for all experimental scenarios. Differences in pharmacokinetics between filgrastim and pegfilgrastim can be explained by different estimates of model parameters rather than by different model mechanisms. Parameter estimates with respect to distribution and clearance of the drug derivatives are in agreement with qualitative experimental results. CONCLUSION: Dynamics of filgrastim and pegfilgrastim plasma levels can be explained by the same pharmacokinetic model but different model parameters. Beause of a strong clearance mechanism mediated by granulocytes, granulocytotic and granulocytopaenic conditions must be studied simultaneously to construct a reliable model. The pharmacokinetic model will be extended to a murine model of granulopoiesis under chemotherapy and G-CSF application.

[Medical palliative therapy of meningiosis carcinomatosa of breast carcinoma with dissociated response in lumbar methotrexate instillation]. / Palliativmedizinische Therapie einer Meningiosis carcinomatosa bei Mammakarzinom mit dissoziierter Response unter lumbaler Methotrexat-Instillation.

CASE REPORT: We report the case of a 51-year-old woman who suffered from breast cancer and developed meningeal carcinomatosis of the brain stem with deafness and blindness. Radiotherapy was given but led to remarkable deterioration of the condition and strong headache. We performed intrathecal therapy with methotrexate (MTX) via lumbar application. Under this regimen, the patient immediately showed complete improvement of the headache and a partial recovery of hearing. There were no side effects apart from alopecia. MTX concentrations in liquor and blood were remarkably inconsistent. 4 weeks after MTX therapy, MRT revealed partial remission of the meningiosis of the brain stem but progression on both hemispheres. 5 weeks after the beginning of the intrathecal therapy, the patient died. CONCLUSION: Despite pharmacokinetic problems we consider lumbar intrathecal therapy with MTX a suitable procedure for patients with leptomeningeal carcinomatosis and poor performance status.

Reduced expression of stromal-derived factor 1 in autonomous thyroid adenomas and its regulation in thyroid-derived cells.

Stromal-derived factor 1 (SDF-1) and CXCR4 comprise a unique chemokine/chemokine receptor pair, exhibiting important functions in morphogenesis and growth regulation as well as attractant properties on T lymphocytes. No data are available on SDF-1 and CXCR4 in normal or pathological thyroid tissues. SDF-1, CXCR4, and CD18 messenger ribonucleic acid (mRNA) as a marker of leukocytic infiltration were quantified in tissues affected by thyroid adenoma (n = 11) and Graves' disease (GD; n = 16) using competitive RT-PCR. SDF-1 mRNA levels differed significantly between autonomous adenomas and the corresponding normal tissue, but not in GD between patients with low or high leukocyte infiltration, thyroid peroxidase, and TSH receptor autoantibodies, respectively. We found a strong correlation between CXCR4 and CD18 mRNA, which indicates CXCR4 expression by leukocytes. To define the cellular source of SDF-1 and CXCR4 in thyroid tissue, we examined various thyroid-derived cells. Fibroblasts are the most potent producers of SDF-1, although thyrocytes also secrete SDF-1 in vitro. Leukocytes showed very weak SDF-1 mRNA levels and no secretion of the chemokine. Immunohistology confirmed and extended these results; SDF-1 expression was found in fibroblasts, but not or very weakly in CD45(+) leukocytes and thyrocytes. Only leukocytes were CXCR4(+). As examined by flow cytometry, the number of CD3(+) T cells expressing CXCR4 is significantly higher in the thyroid than in peripheral blood. SDF-1 seems to be involved in thyroid tissue homeostasis in thyroid adenoma, but not in the maintenance of lymphocytic infiltration in GD.

[Characterization of a monoclonal antibody against a differentiation antigen of human natural killer cells (NK cells)]. / Charakterisierung eines monoklonalen Antikörpers gegen ein Differenzierungsantigen von humanen natürlichen Killerzellen (NK-Zellen).

The new murine monoclonal antibody BL-(H5) reacts with a novel surface molecule which is mainly expressed on human NK and B cells. The antigen is not expressed on peripheral T lymphocytes, thymocytes and different human T-cell lines. BL-(H5) does not bind to erythrocytes and platelets. The monoclonal antibody reacts in western blotting experiments with an antigen of 78kDa.