Cases reported "Kidney Failure, Chronic"

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1/4. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: the induction of allograft tolerance through mixed lymphohematopoietic chimerism.

    BACKGROUND: Experimental and clinical evidence has demonstrated that the establishment of allogeneic chimerism after bone marrow transplantation may provide donor-specific tolerance for solid organ allografts. methods: Based on the preliminary results of a clinical trial using nonmyeloablative preparative therapy for the induction of mixed lymphohematopoietic chimerism, we treated a 55-year-old woman with end stage renal disease secondary to multiple myeloma with a combined histocompatibility leukocyte antigen-matched bone marrow and renal transplant after conditioning with cyclophosphamide, antithymocyte globulin, and thymic irradiation. RESULTS: The posttransplant course was notable for early normalization of renal function, the absence of acute graft-versus-host disease, and the establishment of mixed lymphohematopoietic chimerism. cyclosporine, which was the only posttransplant immunosuppressive therapy, was tapered and discontinued on day 73 posttransplant. No rejection episodes occurred, and renal function remains normal on day 170 posttransplant (14 weeks after discontinuing cyclosporine). Although there is presently no evidence of donor hematopoiesis, there is evidence of an ongoing antitumor response with a recent staging evaluation showing no measurable urine kappa light chains. The patient remains clinically well and is off all immunosuppressive therapy. CONCLUSION: This is the first report of the deliberate induction of mixed lymphohematopoietic chimerism after a nonmyeloablative preparative regimen to treat a hematological malignancy and to provide allotolerance for a solid organ transplant.
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2/4. Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease.

    BACKGROUND: Two patients with end-stage renal disease secondary to multiple myelomas were treated with combined kidney and bone marrow transplantation in an effort to achieve donor-specific allotolerance through the induction of mixed lymphohematopoietic chimerism. methods: Two female patients (55 and 50 years of age) with end-stage renal disease secondary to kappa light-chain multiple myelomas received a nonmyeloablative conditioning regimen that consisted of 60 mg/kg cyclophosphamide intravenously (IV) on days -5 and -4; 15 mg/kg equine anti-thymocyte globulin (ATGAM) IV on days -1, 1, and 3; and thymic irradiation (700 cGy) on day -1. On day 0, the recipients underwent kidney transplantation, followed by IV infusion of donor bone marrow (2.7x10(8) and 3.8x10(8) /kg nucleated cells, respectively) obtained from a human leukocyte antigen (HLA)-matched sibling. cyclosporine A was administered IV at a dose of 5 mg/kg on day -1, then continued orally at 8 to 12 mg/kg per day until days 73 and 77, respectively, after which no further immunosuppression was given. Donor leukocyte infusions (1x10(7) /kg CD3 T cells) were administered in an attempt to enhance the graft-versus-myeloma effect (days 66 and 112 in the first patient and day 78 in the second patient). Hematopoietic chimerism was monitored weekly by microsatellite assays. RESULTS: Multilineage lymphohematopoietic chimerism (5%-80% donor CD3 or CD3- cells, or both) was first detected during the second posttransplant week and was maintained for approximately 12 weeks, after which there was a gradual decline to undetectable levels (<1% donor cells) after day 105 in the first patient and after day 123 in the second patient. In both recipients, the blood urea nitrogen and creatinine levels returned to normal within 3 days. No rejection episodes have occurred. Quantification of urinary kappa light chains revealed a decline from 28 mg/dL to undetectable levels (<2.5 mg/dL) within 29 days in the first case and from 99.8 mg/dL to <10 mg/dL within 50 days in the second case. Both patients continue with normal kidney function and sustained anti-tumor responses, while receiving no immunosuppression for nearly 4 years and 2 years, respectively. CONCLUSIONS: This nonmyeloablative regimen followed by combined HLA-matched donor bone marrow and renal allotransplantation is the first example of an intentional and clinically applicable approach to inducing renal allograft tolerance and achieving potent and sustained antitumor effects in patients with multiple myeloma.
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3/4. Squamous cell carcinoma in a chronically rejected renal allograft.

    The malignant degeneration of a chronically rejected kidney allograft has been rarely reported. Almost invariably such malignancies originated in the transitional epithelium. We herein present the first occurrence of squamous cell carcinoma (SCC), originating from occult donor cells, in a chronically rejected renal allograft. Nearly 20 years after chronic rejection and loss of function of a cadaver renal graft, our patient developed increasing abdominal discomfort, decrease in appetite and weight loss. A CT-scan of the abdomen showed an abnormally enlarged and irregularly contoured mass at the level of the rejected allograft. Given the clinical and radiologic picture suggestive of either an infectious or intraparenchymal hemorrhagic process, a transplant nephrectomy was performed. At surgery, it was immediately evident that a malignant degenerative process had affected the graft. The histological features of the specimen were diagnostic for a well-differentiated SCC. The donor origin of the tumor was established through a dna microchimerism assay performed on the operative specimens. The patient did well after resection of the malignancy, although he died 5 months later owing to a myocardial infarction. In summary, even several years following the transplant, the possibility of a malignancy of donor origin developing within a failed allograft should always be considered as part of the differential diagnosis in unusual post-transplant settings.
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4/4. skin transplantation to monitor clinical donor-related tolerance in mixed hematopoietic chimerism.

    Mixed hematopoietic chimerism usually carries with it the tolerance to any other tissue from the same donor. Consequently, the establishment of a sustained chimerism may allow long-term acceptance of transplanted organs without immunosuppression. We report a girl with refractory severe aplastic anemia who developed low recipient level hematopoietic chimerism following transplantation of maternal highly purified CD34 cells without prophylactic immunosuppression. Renal thrombotic microangiopathy led to chronic renal failure and she received skin allografts from her mother in view of a future kidney donation. The maternal skin grafts were accepted without immunosuppression and the hematopoietic chimerism remained stable. skin transplantation may be a helpful and easily applicable tool to monitor donor-related tolerance in hematopoietic chimerism clinically. It should contribute to minimize the risks of subsequent solid organ transplantation from the same donor without immunosuppression.
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