Blood
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Randomized Controlled Trial Clinical Trial
Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study.
To determine whether cytomegalovirus (CMV) antigenemiaguided ganciclovir treatment may be as effective, may require less treatment, and thus may cause less marrow toxicity than ganciclovir administered at engraftment, 226 marrow transplant recipients were randomized at engraftment to receive placebo (antigenemia-ganciclovir group) or ganciclovir (ganciclovir group) until day 100 in a double-blind study. In patients with antigenemia of 3 or more positive cells in 2 slides and/or viremia, study drug was discontinued and ganciclovir was started for at least 3 weeks or until negative CMV antigenemia and resumed only if antigenemia recurred. More patients in the antigenemia-ganciclovir group developed CMV disease before day 100 after transplantation compared with the ganciclovir group (14% v 2.7%, P = .002). ⋯ In the ganciclovir group, more invasive fungal infections occurred (P = .03) and more ganciclovir was used (P < .0001). Thus, delaying the start of ganciclovir until highgrade antigenemia and discontinuing ganciclovir based on negative antigenemia results in more CMV disease by day 100 than ganciclovir administered at engraftment. However, ganciclovir at engraftment is associated with more early invasive fungal infections and more late CMV disease resulting in similar survival rates.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study.
Interest in high-dose cytarabine (HDAC) for both induction and postremission therapy for acute myeloid leukemia (AML) prompted the Southwest Oncology Group (SWOG) to initiate a randomized trial comparing HDAC with standard-dose cytarabine (SDAC) for remission induction of previously untreated AML and to compare high-dose treatment versus conventional doses for consolidation therapy. Patients less than 65 years of age with de novo or secondary AML were randomized for induction between SDAC 200 mg/ m2/d for 7 days by continuous infusion or HDAC at 2 g/ m2 intravenously every 12 hours for 12 doses; both groups received daunorubicin (DNR) at 45 mg/m2/d intravenously for 3 days. Complete responders to SDAC were randomized to receive either two additional courses of SDAC plus DNR or one course of HDAC plus DNR. ⋯ Induction therapy with HDAC plus DNR was associated with greater toxicity than SDAC plus DNR, but with no improvement in CR rate or survival. Following CR induction with SDAC, consolidation with HDAC increased toxicity but not survival or DFS. In a nonrandomized comparison, patients who received both HDAC induction and consolidation had superior survival and DFS compared with those who received SDAC induction with either SDAC or HDAC consolidation.
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Randomized Controlled Trial Clinical Trial
Effects of granulocyte colony-stimulating factor on plasma cytokine and cytokine receptor levels and on the in vivo host response to endotoxin in healthy men.
We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on cytokine and cytokine receptor plasma levels and on the in vivo host response to Salmonella abortus equi endotoxin in healthy males. Twenty volunteers received 0.8 ng/kg endotoxin and saline intravenously 1 week apart in randomized order. Twelve hours before both experiments, 10 of these subjects were pretreated with 300 micrograms G-CSF subcutaneously. ⋯ Endotoxin-induced increases in IL-6, cortisol, and heart rate were not modified by G-CSF pretreatment. Endotoxin administration induced a transient 50% reduction in leukocyte counts in the G-CSF-pretreated subjects that was not seen in the control group. We conclude that a single stand dose of G-CSF increases the plasma levels of cytokines and cytokine receptors and considerably modifies the host response of healthy humans to a low dose of endotoxin.
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Letter Randomized Controlled Trial Clinical Trial
Oxygen inhalation in nonhypoxic sickle cell patients during vaso-occlusive crisis.
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Randomized Controlled Trial Clinical Trial
Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23).
A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo-controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). ⋯ The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans.