Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B

BACKGROUND: About 65 percent of previously untreated adults with primary acute myeloid leukemia (AML) enter complete remission when treated with cytarabine and an anthracycline. However, such responses are rarely durable when conventional postremission therapy is administered. Uncontrolled trials have suggested that intensive postremission therapy may prolong these complete remissions. METHODS: We treated 1088 adults with newly diagnosed AML with three days of daunorubicin and seven days of cytarabine and randomly assigned patients who had a complete remission to receive four courses of cytarabine at one of three doses: 100 mg per square meter of body-surface area per day for five days by continuous infusion, 400 mg per square meter per day for five days by continuous infusion, or 3 g per square meter in a 3-hour infusion every 12 hours (twice daily) on days 1, 3, and 5. All patients then received four courses of monthly maintenance treatment. RESULTS: Of the 693 patients who had a complete remission, 596 were randomly assigned to receive postremission cytarabine. After a median follow-up of 52 months, the disease-free survival rates in the three treatment groups were significantly different (P = 0.003). Relative to the 100-mg group, the hazard ratios were 0.67 for the 3-g group (95 percent confidence interval, 0.53 to 0.86) and 0.75 for the 400-mg group (95 percent confidence interval, 0.60 to 0.94). The probability of remaining in continuous complete remission after four years for patients 60 years of age or younger was 24 percent in the 100-mg group, 29 percent in the 400-mg group, and 44 percent in the 3-g group (P = 0.002). In contrast, for patients older than 60, the probability of remaining disease-free after four years was 16 percent or less in each of the three postremission cytarabine groups. CONCLUSIONS: These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.     

Validation of a limited sampling model to determine etoposide area under the curve

STUDY OBJECTIVE: To validate the utility of a previously reported 3-point limited sampling model (LSM) for determining etoposide area under the curve to infinity (AUC(infinity)). DESIGN: Secondary analysis of data from two clinical trials of etoposide. SETTING: University medical center clinical research center. PATIENTS: Thirty-four patients with different malignancies. INTERVENTIONS: Etoposide was administered as a 2-hour infusion to 34 patients. Serial plasma samples were drawn over 24 hours after the infusion and analyzed for etoposide by high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: The 3-point LSM AUC was compared with a 14-point actual AUC calculated by the linear trapezoidal rule. Actual and predicted AUC(infinity) by the LSM were highly correlated (r=0.97, p<0.0001). The LSM predictions had a mean absolute error of 10.9% (95% CI -14.1, -5.3) and a mean error of -9.7% (95% CI 6.9, 14.9). Nine patients with poor AUC(infinity) estimations by the LSM (error > 12%) tended to have abnormally low or high peak concentrations. CONCLUSION: Our findings suggest the development of more robust LSM using other techniques, such as pharmacostatistical models, that can accommodate a greater degree of pharmacokinetic variability.     

Anisotropies in visual motion perception: a fresh look

We measured motion-detection and motion-discrimination performance for different directions of motion, using stochastic motion sequences. Random-dot cinematograms containing 200 dots in a circular aperture were used as stimuli in a two-interval forced-choice procedure. In the motion-detection experiment, observers judged which of two intervals contained weak coherent motion, the other internal containing random motion only. In the direction-discrimination experiment, observers viewed a standard direction of motion followed by comparison motion in a slightly different direction. Observers indicated whether the comparison was clockwise or counterclockwise, relative to the standard. Twelve directions of motion were tested in the detection task and five standard directions (three cardinal directions and two oblique directions) in the discrimination task. Detection thresholds were invariant with direction of motion, but direction-discrimination thresholds were significantly higher for motion in oblique directions, even at low-coherence levels. Results from control conditions ruled out monitor artifacts and indicate that the oblique effect is relative to retinal coordinates. These results have broad implications for computational and physiological models of motion perception.     

A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.     

Penicillin vs. erythromycin in the treatment of diphtheria

PURPOSE: To review the University of Florida experience in treating ependymomas, analyze prognostic factors, and provide treatment recommendations. METHODS AND MATERIALS: Forty-one patients with ependymoma and no metastases outside the central nervous system received postoperative radiotherapy with curative intent between 1966 and 1989. Ten patients had supratentorial lesions, 22 had infratentorial lesions, and 9 had spinal cord lesions. All patients had surgery (stereotactic biopsy, subtotal resection, or gross total resection). Most patients with high-grade lesions received radiotherapy to the craniospinal axis. Low-grade intracranial lesions received more limited treatment. Spinal cord lesions were treated using either partial spine or whole spine fields. RESULTS: Of 32 intracranial tumors, 21 recurred, all at the primary site; no spinal cord tumors recurred. Overall 10-year survival rates were 51% (absolute) and 46% (relapse-free); by tumor site: spinal cord, 100%; infratentorial, 45%; supratentorial, 20% (p = 0.002). On multivariate analysis, tumor site was the only factor that influenced absolute survival (p = 0.0004); other factors evaluated included grade, gender, age, duration of symptoms, resection extent, primary tumor dose, treatment field extent, surgery-to-radiotherapy interval, and days under radiotherapy treatment. CONCLUSIONS: Patients with supratentorial or infratentorial tumors receive irradiation, regardless of grade. Craniospinal-axis fields are used when spinal seeding is radiographically or pathologically evident. Spinal cord tumors are treated using localized fields to the primary site if not completely resected. Failure to control disease at the primary site remains the main impediment to cure.     

OSHA's bloodborne pathogens rule an opportunity/threat

If you supply healthcare linen, OSHA's new ruling comes with a price tag, but it may be a marketing boon as well. The costs of compliance are high--about $1.19 million annually. One of the most costly and important parts of the ruling is the required employer-paid hepatitis B vaccination of employees. But behind the costs, there's good news for the textile rental industry. The opportunity to serve small medical facilities and nursing homes as well as hospitals with reusable healthcare garments could create a revenue source estimated to be at least $177 million a year.