The effects of selectively depleting CD8+ cells from donor bone marrow were assessed in 36 patients receiving transplantation from an HLA- identical sibling as treatment for leukemia. Donor bone marrow underwent ex vivo treatment using anti-Leu-2 monoclonal antibody and complement. Patients received cyclosporine post-transplant for 6 months. Thirty-three patients had initial engraftment. Three failed to have hematologic recovery, and one patient with initial engraftment had late graft failure. The actuarial incidence of grade greater than or equal to 2 acute graft-versus-host disease was 28% +/- 18% and was usually confined to the skin. Of 33 patients with engraftment, 32 were complete chimeras and one had mixed chimerism. The tempo of hematologic and immunologic recovery was comparable with that reported with transplantation of unmodified bone marrow, although CD4+ and CD8+ T cells recovered at comparable rates. The actuarial rate of leukemia relapse was 11% +/- 10%, occurring in three patients with acute leukemia but in none of 13 patients transplanted for chronic myelogenous leukemia. Actuarial survival was 57% +/- 17% at 2 years. These data indicate that after transplantation of marrow depleted of CD8+ cells, engraftment with prompt hematologic and immunologic recovery generally occurs, with a relatively low rate of acute graft- versus-host disease. Graft failure remains a problem despite retention of CD4+ cells within the donor marrow. The lack of leukemia relapse in patients with chronic myelogenous leukemia suggests retention of a graft-versus-leukemia effect, at least for this malignancy.
Summary: Twelve patients with primary and metastatic brain tumors were evaluated with [68Galethylene diaminetetraacetate (EDTA ) and positron computed to mography, Using a two-compartment tracer kinetic model, foward (K I ) and reverse (k 2 ) rate constants for molecular diffusion across the blood-brain barrier (BBB) were obtained and averaged 0,0029 ± 0,00 16 (mean ± SD) mllmin/g for K I and 0,03 10 ± 0,0 156 min-I for kz' Most tracer kinetic models are based on the assumption that tissue radioactivity contains no vascular component or require independent measures of cerebral blood volume (CBV) which are then subtracted from the mea sure tissue activity, The model in this work differs from that approach by assuming a vascular compartment in the A loss of integrity of the blood-brain barrier (BBB) increases its permeability to a variety of sub stances (Rapoport, 1976) and forms the presumed pathophysiological mechanism of contrast enhance ment on X-ray computed tomography (CT) scans and tracer uptake in )I-emitting isotope brain-im aging studies. However, it is difficult to quantify the degree of BBB disruption with these methods in physiologic units. Positron CT produces estimates of the local concentrations of administered iso topes. With appropriate tracer kinetic models for these concentration measurements, a variety of
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