Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors

BACKGROUND Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. METHODS We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). RESULTS The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, −3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. CONCLUSIONS We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute–National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.

Epidemiology and outcome of pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) in Canadian hospitals.

BACKGROUND: MRSA remains a leading cause of hospital-acquired (HAP) and healthcare-associated pneumonia (HCAP). We describe the epidemiology and outcome of MRSA pneumonia in Canadian hospitals, and identify factors contributing to mortality. METHODS: Prospective surveillance for MRSA pneumonia in adults was done for one year (2011) in 11 Canadian hospitals. Standard criteria for MRSA HAP, HCAP, ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP) were used to identify cases. MRSA isolates underwent antimicrobial susceptibility testing, and were characterized by pulsed-field gel electrophoresis (PFGE) and Panton-Valentine leukocidin (PVL) gene detection. The primary outcome was all-cause mortality at 30 days. A multivariable analysis was done to examine the association between various host and microbial factors and mortality. RESULTS: A total of 161 patients with MRSA pneumonia were identified: 90 (56%) with HAP, 26 (16%) HCAP, and 45 (28%) CAP; 23 (14%) patients had VAP. The mean (± SD) incidence of MRSA HAP was 0.32 (± 0.26) per 10,000 patient-days, and of MRSA VAP was 0.30 (± 0.5) per 1,000 ventilator-days. The 30-day all-cause mortality was 28.0%. In multivariable analysis, variables associated with mortality were the presence of multiorgan failure (OR 8.1; 95% CI 2.5-26.0), and infection with an isolate with reduced susceptibility to vancomycin (OR 2.5, 95% CI 1.0-6.3). CONCLUSIONS: MRSA pneumonia is associated with significant mortality. Severity of disease at presentation, and infection caused by an isolate with elevated MIC to vancomcyin are associated with increased mortality. Additional studies are required to better understand the impact of host and microbial variables on outcome

Characteristics of patients with healthcare-associated (HCAP), hospital-acquired (HAP), and community-acquired (CAP) methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) pneumonia.

a<p>Appropriate empiric antimicrobial therapy, treatment with vancomycin, linezolid, or clindamycin if the MRSA isolate was susceptible, in the 24-48 hrs prior to the availability of culture results.</p>b<p>Vancomycin trough levels, among those treated with vancomycin and for whom vancomycin levels were available.</p>c<p>PFGE, pulsed-field gel electrophoresis (145 isolates available for molecular typing).</p>d<p>Vancomycin MIC, minimal inhibitory concentration (µg/mL) as determined by Etest (145 isolates available for susceptibility testing).</p

Multivariate analysis of variables associated with 30-day all-cause mortality in patient with methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) pneumonia.

a<p>Appropriate empiric antimicrobial therapy, treatment with vancomycin, linezolid, or clindamycin if the MRSA isolate was susceptible, in the 24-48 hrs prior to the availability of culture results.</p>b<p>Vancomycin MIC, minimal inhibitory concentration (µg/mL) as determined by Etest</p

Variables associated with 30-day all-cause mortality in univariate analysis in patients with methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) pneumonia.

a<p>HCAP, healthcare-associated pneumonia; HAP, hospital-acquired pneumonia; CAP, community-acquired pneumonia</p>b<p>Appropriate empiric antimicrobial therapy, treatment with vancomycin, linezolid, or clindamycin if the MRSA isolate was susceptible, in the 24-48 hrs prior to the availability of culture results.</p>c<p>Vancomycin trough levels, among those treated with vancomycin and for whom vancomycin levels were available.</p>d<p>PFGE, pulsed-field gel electrophoresis (145 isolates available for molecular typing)</p>e<p>Vancomycin MIC, minimal inhibitory concentration (µg/mL) as determined by Etest (145 isolates available for susceptibility testing)</p