A randomized placebo-controlled phase III study of granulocyte- macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490)

The treatment of adult patients greater than 55 to 70 years of age with acute myelogenous leukemia (AML) is associated with a treatment-related mortality of approximately 25%. This prospective, double-blind randomized study was designed to see if the use of granulocyte- macrophage colony stimulating factor (GM-CSF; yeast-derived) could shorten the period of neutropenia and to determine any effect this would have on therapy-related morbidity and mortality. A total of 124 patients entered this study. Induction consisted of standard daunorubicin and cytarabine. A day-10 bone marrow was examined; if this was aplastic without leukemia, patients received blinded placebo or GM- CSF from day 11 until neutrophil recovery. Patients who entered complete remission received the identical study medication (blinded GM- CSF or placebo) in consolidation that they had received during induction. The overall complete remission rate was 52%; 60% for the GM- CSF arm and 44% for the placebo arm (P = .08). Median times to neutrophil recovery were significantly shortened on the GM-CSF arm. The overall treatment-related toxicity from start of GM-CSF/placebo was reduced on the GM-CSF arm (P = .049). Similarly, the infectious toxicity was significantly reduced on the GM-CSF arm (P = .015). The median survival for all patients was 10.6 months in the GM-CSF group and 4.8 months in the placebo arm (P = .048). It appears that GM-CSF is safe and efficacious for adult patients greater than 55 to 70 years of age with AML; its major impact is in reducing the duration of neutropenia and therapy-related mortality and morbidity. This may result in a better response rate.     

Human leukocyte cathepsin G and elastase specifically suppress thrombin- induced prostacyclin production in human endothelial cells

Polymorphonuclear leukocytes (PMN) when activated release products that can potentially injure endothelial cells or alter endothelial function. Exposure of cultured human umbilical vein endothelial cells to cathepsin G and elastase isolated from human PMN at concentrations reached in vivo (100 ng/mL to 10 micrograms/mL) selectively inhibited thrombin-induced prostacyclin production and the thrombin-induced rise in cytosolic free calcium ([Ca++]i) concentration. These proteases also blocked thrombin-induced release of arachidonic acid from prelabeled endothelial cells (EC). In contrast, induction of prostacyclin (PGI2) production by arachidonate, histamine, or the calcium ionophore A23187 was not altered by treatment of EC with these proteases. The effects of the proteases were concentration-dependent, were blocked by serum or serum protease inhibitors, and were reversed when the endothelial cells were further cultured for 24 hours in the absence of the proteases. Elastase, but not cathepsin G, also produced detachment of endothelial cells. Thus, the major leukocyte proteases selectively suppress thrombin-induced prostacyclin production by human vascular endothelial cells and may alter the hemostatic balance at sites of PMN activation.     

Laparoscopic adrenalectomy and splenectomy are safe and reduce hospital stay and charges

The proposed benefits of laparoscopy for certain surgical procedures have been decreased post-operative pain and hospital stay balanced against the proposed deficits of increased costs. We have reviewed our data to evaluate factors associated with patient, procedure, and hospital charges for patients undergoing open versus laparoscopic adrenalectomy and splenectomy during the same time period. Eighty-seven patients underwent adrenalectomy (n = 47) or splenectomy (n = 40) from October 30, 1995 to June 6, 2001 and were retrospectively reviewed. Patient and operative factors were analyzed by intent to treat; the major endpoints were operating room (OR) time in minutes, blood loss in cm3, length of hospital stay in days, and charges broken down by anesthesia/operation [OR/recovery room (RR)] and total charges in dollars x 1000. Comparisons of means were analyzed by unpaired t test; data are presented as mean +/- SEM, and significance is defined as P < 0.05. Median age of the group was 47 years (range 20-77). Forty-five patients underwent a laparoscopic approach of which two were converted to open (4%) as compared with 42 undergoing an open operation; one patient from each group was excluded from outcome analyses because of prolonged hospitalization (>3 weeks). Operative mortality of the whole group was one per cent. There were no differences between the groups with respect to age, gender, or comorbidity. The laparoscopic group had significantly longer operative times and OR/RR charges. However, the length of hospital stay and the total charges for the patient undergoing a laparoscopic approach were significantly less (P < 0.05). We conclude that a laparoscopic approach for adrenalectomy or splenectomy can be accomplished in approximately 95 per cent of patients selected for this procedure. Despite prolonged OR time and increased OR/RR charges the laparoscopic procedures resulted in significantly decreased length of hospital stay and overall patient charges. Laparoscopy is a safe and cost-effective approach and should be strongly considered in patients requiring adrenalectomy or splenectomy.