Horsies and bunnies: A comparison of antithymocyte globulin in allogeneic stem cell transplant.

: Graft versus host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplant (HSCT). In vivo T-cell depletion includes antithymocyte globulin (ATG) such as ATG-Horse or ATG-Rabbit used in combination with a calcineurin inhibitor and low dose methotrexate to decrease the incidence of GVHD in HSCT recipients. This method of broad T-cell depletion has decreased the incidence, severity and treatment refractoriness of chronic GVHD. Objective: The goal of this study is to describe the impact of transitioning from ATG-Horse to ATG-Rabbit at Henry Ford Hospital located in Detroit, Michigan. The primary endpoint is the incidence of chronic GVHD after switching products. Secondary endpoints include: incidence of acute GVHD, cumulative incidence of CMV reactivation, average length of stay, incidence of hypersensitivity reactions, and overall incidence of infection. A final cost analysis was performed to highlight financial savings. Methods: This retrospective non-inferiority study evaluated the clinical outcomes of unrelated HSCT patients who received ATG to prevent GVHD. Patients from January 2005 to December 2015 were included in the study if they were adults greater than 18 years old who received an allogeneic unrelated HSCT (peripheral or bone marrow) with ATGHorse or ATG-Rabbit. Results: There were no statistically significant differences in incidence of acute and chronic GVHD between both ATGRabbit and ATG-Horse groups. The one-sided confidence interval was .21, which exceeds the pre-specified noninferiority margin of .15, thus non-inferiority cannot be concluded. Overall length of stage was statistically significantly shorter in ATG-Rabbit group by 3 days. Total cost savings from 2011-2016 with the switch of ATG agents was $570,036.18, or$6,552.14 per patient. Conclusion: Despite not meeting the hypothesis that ATGRabbit is non-inferior to ATG-Horse, there is still benefit in ease of administration and decreased length of stay, which validates the continual use of ATG-Rabbit in allogeneic unrelated HSCT patients

Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project.

Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass 215 spectrometry through a worldwide collaboration. Methods: Cumulative percentiles of amino 216 acids and acylcarnitines in dried blood spots of approximately 30 million normal newborns and 217 10,615 true positive cases are compared to assign clinical significance, which is achieved when 218 the median of a disease range is either >99%ile or <1%ile of the normal population. The cutoff 219 target ranges of analytes and ratios are then defined as the interval between the limits of the two 220 populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity 221 taking in consideration all available factors. Results: As of December 1, 2010, 129 sites in 45 222 countries have uploaded to the project website a total of 23,970 percentile data points, 558,168 223 analyte results of 10,615 true positive cases with 64 conditions, and 5,088 cutoff values. The 224 average rate of submission of true positive cases between December 1, 2008 and December 1, 225 2010 was 4.7 cases per day (3,418 cases). This cumulative evidence generated 91 and 23 high 226 and low target cutoff ranges, respectively. The overall proportion of cutoff values within the 227 respective target range was 43% (2,176/5,088). Conclusions: An unprecedented level of 228 cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 229 markers applied to newborn screening of rare metabolic disorders. This set of data could be used 230 as baseline for monitoring of future performance

Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project

PURPOSE:: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. METHODS:: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration. RESULTS:: As of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341). CONCLUSION:: An unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders. © 2011 Lippincott Williams &amp; Wilkins