Current opinion in hematology
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Curr. Opin. Hematol. · May 2006
ReviewRecent advances in globin gene transfer for the treatment of beta-thalassemia and sickle cell anemia.
The beta-thalassemias and sickle cell anemia are severe congenital anemias for which there is presently no curative therapy other than allogeneic hematopoietic stem cell transplantation. This therapeutic option, however, is not available to most patients due to the lack of an HLA-matched bone marrow donor. The transfer of a regulated globin gene in autologous hematopoietic stem cells is therefore a highly attractive alternative treatment. This strategy, simple in principle, raises major challenges in terms of controlling transgene expression, which ideally should be erythroid specific, differentiation and stage restricted, elevated, position independent, and sustained over time. ⋯ These recent advances bode well for the clinical investigation of stem cell-based gene therapy in the severe hemoglobinopathies.
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Despite the excellent clinical results with imatinib in chronic myeloid leukemia, most patients have minimal residual disease and others will develop resistance and may eventually progress. Thus there is a need for developing approaches to overcome and prevent resistance to imatinib. ⋯ Multiple effective agents are being developed to overcome resistance to imatinib. The challenge for the future is to incorporate them into effective strategies that can eliminate the disease and cure all patients with chronic myeloid leukemia.
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Curr. Opin. Hematol. · Jan 2006
ReviewNeutrophil granule contents in the pathogenesis of lung injury.
This review summarizes recent literature on the role of neutrophil granule contents in acute lung injury and the mechanisms by which these contribute to inflammatory tissue injury. ⋯ The primary function of neutrophils in the innate immune response--to contain and kill invading microbial pathogens--is achieved through a series of rapid and coordinated responses culminating in phagocytosis and intracellular killing of the pathogens. Neutrophils have a potent antimicrobial arsenal that includes oxidants, proteinases, and cationic peptides. Reactive oxygen species such as oxygen are produced by the phagocyte NADPH oxidase and are microbicidal. Granules within the neutrophil cytoplasm contain potent proteolytic enzymes and cationic proteins that can digest a variety of microbial substrates. These compounds are released directly into the phagosome, compartmentalizing both the pathogen and the cytotoxic products. Under pathological circumstances, however, unregulated release of microbicidal compounds into the extracellular space can paradoxically damage host tissues. Nonspecific inhibition of neutrophils is not clinically realistic, as it would leave the host vulnerable to infection. As the mechanisms of action of neutrophil granule contents are elucidated, therapeutic targets will be identified that will allow for suppression of neutrophils' detrimental effects while avoiding inhibition of their beneficial effects.
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Curr. Opin. Hematol. · Nov 2005
ReviewPretransfusion trigger platelet counts and dose for prophylactic platelet transfusions.
To assess critically both the blood platelet counts that prompt a platelet transfusion (i.e. trigger) in various clinical settings in patients with thrombocytopenia caused by marrow failure and the dose of platelets infused (i.e. number per each transfusion) for optimal hemostasis, feasibility, and safety. ⋯ Reasonable clinical practice, until more definitive data become available, is to transfuse enough platelets per each transfusion to maintain the blood platelet count >10 x 10/L in stable nonbleeding patients, >20 x 10(9)/L in unstable nonbleeding patients, and >50 x 10(9)/L in bleeding patients or in those undergoing invasive procedures.
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Massive blood transfusion saves the lives of thousands of severely injured patients each year, but it does so in the context of the evolving epidemiology of injury, of trauma centers and trauma systems, and of blood safety and new technologies for hemorrhage control. This article reviews recent knowledge and advances that impact on the use and effectiveness of massive transfusion. ⋯ Injury is a major public health and medical system problem. Progress in basic science, clinical care, and the development of better hemorrhage control devices are all improving outcome for massively transfused patients. Investment in trauma care and supporting blood supply systems is highly cost effective.