Current opinion in hematology
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Curr. Opin. Hematol. · May 2000
ReviewUses of granulocyte-macrophage colony-stimulating factor in vaccine development.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent cytokine capable of inducing differentiation, proliferation, and activation of a variety of immunologically active cell populations. In addition to its effects on stimulating granulocytic hematopoiesis, it also facilitates development of both humoral and cellular mediated immunity. ⋯ Because of the potency of this cytokine as an immune adjuvant, particular interest has focused on its use to overcome poorly immunogenic antigens such as those associated with intracellular infections and cancer. This review focuses on recent advances in the use of GM-CSF as a vaccine adjuvant.
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Curr. Opin. Hematol. · Nov 1999
ReviewBone marrow transplantation for globoid cell leukodystrophy, adrenoleukodystrophy, metachromatic leukodystrophy, and Hurler syndrome.
Bone marrow transplantation protocols for inherited metabolic storage diseases are unique for each disorder treated. Differences depend also upon how old the patient was when onset occurred and rate of progression of disease. Treatment is directed to prevent or ameliorate the inexorable neurological deterioration that is the major pathophysiological event in all of these inherited metabolic storage diseases.
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Curr. Opin. Hematol. · Nov 1999
ReviewPathophysiology of febrile nonhemolytic transfusion reactions.
Most febrile nonhemolytic transfusion reactions (FNHTR) to platelets are caused by cytokines that accumulate in the product during storage. There have been numerous studies that have demonstrated high concentrations of leukocyte- and platelet-derived cytokines in stored platelet products. The mechanism of cytokine accumulation is not understood; however, recent studies have suggested that leukocyte apoptosis and/or monocyte activation during the manufacturing process may play a role. ⋯ Hence, it appears that most febrile nonhemolytic transfusion reactions to erythrocytes are probably the result of an incompatibility between leukocytes in the erythrocyte product and antibodies in the recipient's plasma. Recent studies have confirmed that the concentrations of proinflammatory cytokines in a wide variety of stored erythrocyte products are low. Also, there is no clinical evidence to suggest that the small quantities of cytokines present in stored erythrocyte products contribute to acute reactions to these products when transfused.
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Curr. Opin. Hematol. · May 1999
ReviewAugmentation of the immune response with granulocyte-macrophage colony-stimulating factor and other hematopoietic growth factors.
Granulocyte-macrophage colony-stimulating factor is by far the most widely used hematopoietic growth factor to augment immune responses. At present, the best secured effect is as an adjuvant cytokine for vaccination. Granulocyte-macrophage colony-stimulating factor can be delivered as gene-transduced tumor cells, as plasmid DNA, or as the soluble free granulocyte-macrophage colony-stimulating factor protein. ⋯ It may also be advantageous to combine granulocyte colony-stimulating factor with monoclonal antibodies (neutrophil and monocyte antibody-dependent cellular cytotoxicity) for tumor therapy. However, these growth factors might also induce immune suppression, which may hamper the contemplated effect of the growth factor. It is urgently warranted to better understand these dual effects on the immune system so that we can find optimal uses for the growth factors in various clinical settings.
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Curr. Opin. Hematol. · May 1999
ReviewRole of hematopoietic growth factors in non-neutropenic infections and sepsis.
Therapy with colony-stimulating factors has been extended beyond their use in accelerating myeloid cell recovery to take advantage of their immune function-enhancing properties. Studies in animal models and with human subjects suggest a potential role as adjunctive therapy in infections of non-neutropenic hosts, including those with sepsis. ⋯ Significant issues of exogenous colony-stimulating factor therapy must be addressed, however: the optimal timing, dose, and clinical context (e.g., type of immunosuppression, duration of infection-inciting stimulus) as well as tissue-specificity of the activities and net effect of potentially conflicting responses (e.g., immune restorative and procoagulant effects of granulocyte macrophage colony-stimulating factor). Resolution of these issues will require carefully designed clinical studies with meticulous monitoring of immunologic parameters.