The high mortality of marrow graft recipients with chronic graft-versus- host disease (GVHD) is due to common bacterial infections developing in the presence of a poor humoral immune response to polysaccharide antigens. As more patients receive grafts from donors other than HLA-identical siblings, the incidence of chronic GVHD rises and results in a higher number of long- term patients with infections increasing the significance of this complication. In this proposal the investigators plan to address this issue of susceptibility to bacterial infection using a two-pronged approach. The first is to investigate immunization strategies utilizing the commercially available Hemophilus influenzae-diphtheria conjugate vaccine or the conjugate vaccine administered with interleukin-2 to trigger a normal response in long term patients with chronic GVHD. If successful, this approach could be applied to protection from infection with other bacteria bearing polysaccharide antigens such as the pneumococci. The second is to use an in vitro assay of immunoglobulin production to document the immune deficiency of B lymphocytes from patients with and without chronic GVHD who received unrelated donor marrow grafts and determine whether the deficiency can be altered in vitro by addition of lymphokines to culture. The results of these in vitro studies could lead to clinical trials of lymphokine administration to augment B lymphocyte growth and development and reduce susceptibility to infection in long-term survivors of marrow transplantation.
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