Seminars in hematology
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Imatinib (Gleevec) (formerly STI571) is an orally bioavailable rationally developed inhibitor of the tyrosine kinases Bcr-Abl, Kit, and platelet-derived growth factor receptor (PDGFR). In 4 years of clinical development, more than 12,000 patients have been treated in the clinical development program. ⋯ Imatinib has also been shown to be the only effective drug therapy in the treatment of patients with metastatic gastrointestinal stromal tumors expressing the stem cell factor (SCF) receptor Kit. This review outlines the successive steps in the clinical development of this new, targeted anticancer agent.
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Seminars in hematology · Jul 2002
ReviewActivated protein C: potential therapy for severe sepsis, thrombosis, and stroke.
Activated protein C (APC) reduced all-cause 28-day mortality by 19% in patients with severe sepsis (sepsis associated with acute organ dysfunction) in the Protein C Evaluation in Severe Sepsis (PROWESS) trial, leading to recent approval of recombinant APC for treatment of this condition in adults. This review summarizes current knowledge derived from studies of a variety of animal models in which infused human APC demonstrated beneficial activities. ⋯ APC is a normal circulating component of plasma, derived from the protein C zymogen, and is thus a natural endogenous protective homeostatic factor. Because of its multiple activities, APC has a potential role in the treatment of complex and challenging medical disorders, including thrombosis and stroke.
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Anemia is a common clinical problem in critically ill patients and is associated with substantial red blood cell (RBC) transfusion requirements. However, RBC transfusion has significant risks, including adverse effects on the immune system. Although a low hemoglobin concentration may be tolerable, it may not be optimal for the critically ill patient. ⋯ Results of a recent randomized controlled trial in critically ill patients demonstrated that recombinant human erythropoietin (r-HuEPO, epoetin alfa) significantly reduced (by approximately 50%) the number of RBC units transfused (P <.002) and significantly increased hematocrit (P <.01) compared with placebo. There was no increase in mortality or adverse clinical events with therapy. Epoetin alfa may be an effective therapeutic approach to anemia in critically ill patients, decreasing the need for transfusion and achieving higher hemoglobin concentrations than generally attained with transfusion.
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Seminars in hematology · Jul 2001
ReviewCurrent use and future development of gemtuzumab ozogamicin.
The antigen CD33 is expressed on blast cells in 80% to 90% of acute myeloid leukemia (AML) cases but, importantly, is not expressed on pluripotent hematopoietic stem cells or on nonhematologic cells. Gemtuzumab ozogamicin (CMA-676) uses a recombinant humanized anti-CD33 monoclonal IgG4 antibody to deliver the potent cytotoxin, calicheamicin, into cells. Three multicenter trials have evaluated the efficacy and safety of gemtuzumab ozogamicin as a single agent in 142 patients with CD33+ AML in untreated first relapse. ⋯ Severe hyperbilirubinemia (23%) and elevated hepatic transaminases (18%) were usually transient. Among all 142 patients, the median total hospitalization was 24 days; 16% of patients required < or = 7 days in hospital. Additional studies are currently evaluating gemtuzumab ozogamicin in combination with, or as an alternative to, other standard AML chemotherapy.
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Seminars in hematology · Jan 2001
ReviewCurrent issues with blood transfusions in sickle cell disease.
With increased recognition of the profound morbidity of sickle cell disease and with growing evidence of the efficacy of transfusion therapy in prevention and treatment of sickle cell complications, most patients now receive intermittent transfusion therapy. The purpose of this report is to review blood component therapy and Its risks for sickle cell patients. Packed red cells are the preferred blood component. ⋯ In part, these are induced by blood viscosity and increased blood pressure. Diuretic therapy and close monitoring of transfusion volume and vital signs can minimize these events. In summary, transfusion therapy carries risks, but the routine use of leukocyte-reduced, phenotypically matched units in conjunction with close monitoring of patients can make transfusion therapy safer.