T4+ cells can initiate human graft-versus-host disease.
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Biomedical subjects
Publications and source records attributed to E O'Flaherty.
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Sixteen patients with haematological malignancy received high-dose chemotherapy or chemotherapy and total body irradiation followed by an HLA-identical sibling marrow transplant from which the T lymphocytes had been depleted prior to infusion by incubation with an anti-CD2 anti-T cell antibody with (seven patients) or without (nine patients) an anti-CD8 anti-T cell antibody together with rabbit complement. Additionally, all patients received cyclosporin. The number of T cells present in the donor marrow was determined by limiting dilution analysis, and was found to correlate with the subsequent incidence and severity of acute graft-versus-host disease (GVHD). The number of T cells infused into patients with no acute GVHD or with minimal acute GVHD of the skin (skin rash present for 14 days or less) was 1.3 +/- 1.0 x 10(5)/kg, while the number infused into those with moderate acute GVHD or with skin acute GVHD present for 15 days or more was 12.3 +/- 11.5 x 10(5)/kg (p less than 0.001). Thus a dose of 10(5) (or less) T cells/kg was associated with minimal or no acute GVHD, while 10(6) T cells/kg (or more) caused significant disease.
This study was performed to determine the effect of coadministered oral metoclopramide on the absorption of oral cyclosporine in 14 kidney transplant patients with stable renal function. The study was conducted on two consecutive days. Ten patients were studied twice and four patients once, giving 24 studies. The total dosage of metoclopramide was 20 mg. The day on which metoclopramide was administered was chosen randomly. Whole blood cyclosporine levels were analyzed by high performance liquid chromatography. Coadministration of cyclosporine with metoclopramide resulted in a significant increase in mean maximum blood concentration (567 ng/mL nu 388 ng/mL) and mean area under the blood concentration nu time curve (4120 ng X h/mL nu 3370 ng X h/mL), and a significant decrease in mean time to reach maximum concentration: The mean increase in area under the blood concentration versus time curve was 29%. No significant changes were observed in the elimination of cyclosporine when it was coadministered with metoclopramide. These observations suggest that coadministered metoclopramide increased the total absorption of cyclosporine. Metoclopramide has been shown to hasten gastric emptying; since cyclosporine is absorbed predominantly in the small intestine, coadministration of metoclopramide resulted in increased bioavailability of cyclosporine.
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Recent reports have highlighted an associated of pure red cell aplasia (PRCA) with myelodysplasia (MDS). There are minimal data on the response of PRCA in this context to immunosuppression; in particular the role of cyclosporin A (CSA) has not been evaluated. We describe a patient with PRCA/MDS in whom CSA and low dose prednisolone led to restoration of marrow erythropoietic activity. Tests indicated the PRCA was likely to be mediated by cytotoxic lymphocytes rather than an inhibitory effect of cytokines. These observations suggest that CSA, due to its suppressive effect on cytotoxic T cell activity, is a rational therapy in this context.
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