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Background Accelerate Pheno blood culture detection system (AXDX) provides rapid identification and antimicrobial susceptibility testing results. Limited data exist regarding its clinical impact. Other rapid platforms coupled with antimicrobial stewardship program (ASP) real-time notification (RTN) have shown improved length of stay (LOS) in bacteremia. Methods A single-center, quasi-experimental study of bacteremic inpatients before and after AXDX implementation was conducted comparing clinical outcomes from 1 historical and 2 intervention cohorts (AXDX and AXDX + RTN). Results Of 830 bacteremic episodes, 188 of 245 (77%) historical and 308 (155 AXDX, 153 AXDX + RTN) of 585 (65%) intervention episodes were included. Median LOS was shorter with AXDX (6.3 days) and AXDX + RTN (6.7 days) compared to historical (8.1 days) (P = .001). In the AXDX and AXDX + RTN cohorts, achievement of optimal therapy (AOT) was more frequent (93.6% and 95.4%, respectively) and median time to optimal therapy (TTOT) was faster (1.3 days and 1.4 days, respectively) compared to historical (84.6%, P ≤ .001 and 2.4 days, P ≤ .001, respectively). Median antimicrobial days of therapy (DOT) was shorter in both intervention arms compared to historical (6 days each vs 7 days; P = .011). Median LOS benefit during intervention was most pronounced in coagulase-negative Staphylococcus bacteremia (P = .003). Conclusions LOS, AOT, TTOT, and total DOT significantly improved after AXDX implementation. Addition of RTN did not show further improvement over AXDX and an already active ASP. These results suggest that AXDX can be integrated into healthcare systems with an active ASP even without the resources to include RTN.

Aim/purpose Bloodstream candida infections can seed the eye via hematogenous spread and result in chorioretinitis or endophthalmitis. If undetected and untreated, this can result in permanent vision loss. Past studies evaluating incidence of ocular candidiasis among hospitalized patients with positive fungal blood cultures have demonstrated variable rates of occurrence, but recent studies have generally shown a lower incidence than was reported several decades ago. Given low rates of occurrence, the utility of screening patients with dilated fundus exams has been called into question. The primary aim of this investigation is to identify the rate of chorioretinitis and endophthalmitis based on dilated fundoscopy for patients with fungemia at a tertiary care hospital. Methods This study was a retrospective chart review of adult patients admitted to the medical centre of the University of Arkansas for Medical Sciences (UAMS) between May 1, 2014 and December 31, 2017, who had positive fungal blood cultures during their hospitalization. Results There were 324 positive fungal cultures in 290 patients. Of this initial group, there were 161 eye exams. Ocular examination identified 7 of 161 patients (4.3%) with chorioretinitis or endophthalmitis. Discussion These outcomes along with previous studies support the current guidelines that screening with dilated fundus examination for these patients is appropriate and necessary.

Background Phe-restricted diets have been the basis of therapy for phenylketonurics; however, little is known how this treatment effects homeostasis of other important amino acids. This study aimed to describe blood amino acid patterns in neonates with phenylketonuria (PKU) and identify any effects of Phe restriction on these patterns in young children.Methods Neonate group (age 0-4 weeks): 45 PKU patients, 45 age-/sex-matched controls without PKU; 1-4 year-old group: 27 diet-treated PKU patients, 27 age-/sex-matched children without PKU. Concentrations of 11 amino acids were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) performed on dried blood spots.Results Elevated blood phenylalanine (Phe), arginine (Arg), citrulline (Cit), valine (Val) and methionine (Met) concentrations were observed in PKU neonates relative to controls (Phe, Arg, Cit, Val: P < 0.001; Met: P < 0.05), of which Phe, Arg, and Met levels could be either partially or completely restored with dietary intervention. Diet had no effect on elevated Cit and Val. Decreased blood tyrosine (Tyr) and proline (Pro) concentrations were observed in PKU neonates compared to controls (P < 0.001). Both amino acids could be near completely restored to normal with dietary treatment. No significant differences in alanine (Ala), leucine (Leu), ornithine (Orn) and glycine (Gly) concentrations were found in the PKU neonates and 1-4 year-old groups (P > 0.05).Conclusions Blood amino acid homeostasis is disrupted in neonates and young children with PKU. Although dietary intervention adjusts amino acid homeostasis in the direction of a healthy equilibrium, complete restoration is not achieved. This persistent disruption may represent a clinically significant barrier to achieving the best possible therapy for those with PKU. Use of laboratory technologies such as LC-MS/MS enable characterization of persistent blood amino acid disequilibrium in the treated phenylketonuric. Testing of this kind presents opportunity for customized treatment feedback that may allow even greater optimization of therapy for neonates and children with PKU.

BackgroundData from the Improving Outcomes and Antibiotic Stewardship for Patients with Bloodstream Infections: Accelerate PhenoTest™ BC Kit (AXDX) Registry Study were analysed to determine the impact of rapid organism identification and antimicrobial susceptibility testing (AST) for Gram-positive bacteraemia.Patients and methodsThis multicentre, quasi-experimental study evaluated clinical and antimicrobial stewardship metrics following the implementation of AXDX. Data from hospitalized patients with bacteraemia were compared between groups, one that underwent testing on AXDX (post-AXDX) and one that underwent traditional identification and AST (pre-AXDX). An analysis of patients with Gram-positive bacteraemia was performed. The primary outcome was time to optimal therapy (TTOT). Secondary outcomes included time to first antibiotic modification (overall and Gram-positive), duration of unnecessary MRSA coverage, incidence of adverse events, length of stay and mortality.ResultsA total of 219 (109 pre-AXDX, 110 post-AXDX) patients with Gram-positive bacteraemia were included. Median TTOT was 36.3 h (IQR, 16.9–56.7) in the pre-AXDX group and 20.4 h (IQR, 7.5–36.7) in the post-AXDX group (P = 0.01). Compared with pre-AXDX, median time to first antibiotic modification (29.1 versus 15.9 h; P = 0.002), time to first Gram-positive antibiotic modification (33.2 versus 17.2 h; P = 0.003) and median duration of unnecessary MRSA coverage (58.4 versus 29.7 h; P = 0.04) were reduced post-AXDX. A trend towards decreased acute kidney injury (24% versus 13%; P = 0.06) was observed in the post-AXDX group. Groups did not differ in other secondary outcomes.ConclusionsImplementation of AXDX testing for patients with Gram-positive bacteraemia shortened the TTOT and reduced unnecessary antibiotic exposure due to faster antibiotic modifications.

BACKGROUND Although most cases of Hansen disease (HD) in the United States are imported from endemic areas, a subset of cases are relate to exposure to nine-banded armadillos. Several recent cases of HD in Arkansas occurred in patients who had not traveled to endemic areas and who reported variable degrees of armadillo exposure. OBJECTIVE The purpose of this study was to report 6 cases of HD diagnosed in Arkansas between 2004 and 2016. The secondary purpose was to explore the correlation between exposure to the nine-banded armadillo as it pertains to transmission of the disease. METHODS The referring clinician of each patient was contacted to gather information regarding the patient's clinical presentation, armadillo exposure, and travel history. In addition, the Arkansas Department of Health was consulted to review the demographics of individuals diagnosed with HD in the past 15 years and to review the distribution of HD throughout the state of Arkansas. RESULTS Six domestic cases of HD were associated with both direct and indirect exposure to armadillos. LIMITATIONS Armadillo exposure may be underreported in patients with HD because of fear of stigmatization and/or lack of access to care. CONCLUSIONS Direct exposure to armadillos does not appear to be required for transmission of HD making a soil-mediated mechanism of indirect exposure plausible.

A patient with asplenia and multiple red blood cell transfusions acquired babesiosis infection with Babesia divergens-like/MO-1 organisms and not Babesia microti, the common United States species. He had no known tick exposure. This is believed to be the first transfusion-transmitted case and the fifth documented case of B. divergens-like/MO-1 infection.

We report a case of Rhizopus keratitis in a young woman with poor contact lens hygiene. The mold was highly sensitive to treatment with amphotericin 0.15% drops, after a relatively prompt diagnosis. Obtaining cultures of both corneal infiltrates and presumably infected contact lenses may help to avoid a delay in proper treatment.

Thrombotic thrombocytopenic purpura (TTP) results from a congenital or acquired deficiency of the von Willebrand factor (vWF)-cleaving protease ADAMTS13. The disease can be fatal and hence treatment should be initiated promptly. Therapeutic plasma exchange (TPE) remains the standard treatment along with adjunct therapies including steroids and immunosuppressive drugs. Addition of rituximab to TPE has been shown to be beneficial in refractory/relapsing TTP; however, TPE results in removal of rituximab from the circulation requiring more frequent dosing of rituximab to achieve a favorable outcome. The intermediate-purity plasma-derived Factor VIII concentrate (FVIII) Koate® contains the highest amount of ADAMTS13 activity yet reported and has been used successfully in treating congenital TTP. Here we report our experience with addition of this FVIII concentrate to rituximab, corticosteroids and TPE in three TTP patients with an ADAMTS13 inhibitor to permit withholding TPE for 48 h after rituximab infusion.

Panel reactive antibody (PRA) reduction protocols are used to decrease anti-HLA antibodies with concomitant PRA monitoring as a measure of successful treatment prior to organ and haploidentical blood and marrow transplant (BMT). We hypothesized that the more sensitive flow cytometry (FC) based assays for PRA [FlowPRAA female patient with myelodysplastic syndrome and a high HLA class I PRA [90% PRA and cPRA by complement-dependent cytotoxicity (CDC) assay and Flow PRA] required allogeneic BMT. Baseline HLA Class I and class II antigen typing was performed and a matched sibling donor was identified. Although baseline anti-HLA class I and class II antibodies measured by FC and CDC revealed no donor specific antibodies (DSA), the decision was made to attempt antibody desensitization to facilitate platelet transfusion during BMT. FC and CDC assays were performed to determine anti-HLA class I antibodies and cPRA/%PRA prior to starting desensitization and at the end of desensitization. Over the course of desensitization and BMT, a total of 194 apheresis platelet units underwent cross-match (XM) using Capture-PHigh PRA by FC or CDC assays correlates with a high % of XM-positive (incompatible) platelet units. When the CDC PRA fell to 2% after desensitization, platelet XM incompatibility fell from 100% to 63% positive (incompatible). When the FC PRA fell to 5% the positive platelet XM fell to 5%.Antibody desensitization facilitated platelet transfusion. PRA determination by FC appeared better correlated than determination by CDC with the ability to find XM-compatible platelets.

Background Clostridium difficile infection (CDI) remains a major health problem in the United States. The IDSA guidelines recommend using stool toxin assay as part of a multistep algorithm rather than nucleic acid amplification test (NAAT) alone. However, the clinical significance of toxin negative tests remains a subject of debate. We performed a prospective study in our institution to describe clinical outcomes of CDI based on the results of the stool toxin assay. Methods Our laboratory utilizes a 2-step algorithm, using glutamate dehydrogenase plus detection of toxin B by enzyme immunoassay (EIA) arbitrated by NAAT for testing stool samples submitted for C. difficile testing. The study was conducted between January and December 2017. Patients diagnosed with CDI based on laboratory results were divided into two groups based on toxin B assay results. Shotgun metagenomics was performed directly on stool specimens using Illumina NextSeq in a subset of patients. Chart reviews were performed to assess clinical outcomes. Our primary outcome was incidence of severe CDI and 30-day mortality. Results A total of 2,823 samples were submitted to the laboratory for testing for suspected CDI. Three hundred thirty-eight samples in 290 discrete patients were considered positive using the two step algorithm. Whole genome sequencing was performed on samples from 57 patients (Figure 1). Clinical outcome data were available for 53 patients. Thirty percent were on active chemotherapy. Thirty-four patients were toxin B positive (group 1), 19 were toxin B negative (group 2) by EIA. Hospital onset disease was seen in 10 (27%) of patients in group 1 vs. 7 (37%) in group 2 (P = 0.57). Thirty-day mortality was 3% in toxin positive vs. 5% in toxin negative groups (P = 0.67). Severe CDI was seen in 14 (41%) in group 1 vs. 8 (42%) in group 2 (P = 0.94). NAP 1 strain was detected in 10.5% of patients in group 2. Percentage of C. difficile reads on sequencing in fecal samples in group 1 (0.17%) was not significantly different from group 2 (0.24%) (P = 0.70, Figure 2). Conclusion In our cohort, detection of C. difficile toxin in stool samples was not associated with increased severity of disease. Our cohort has a higher prevalence of patients on active chemotherapy than previously studied cohorts. Bioburden of C. difficile was not significantly different in toxin positive and negative disease. Disclosures All authors: No reported disclosures.

Mobilization regimens for CD34+ cells have generally been judged successful based on the number of cells collected without evaluating mobilization separately from collection. Using retrospective data for patients who collected CD34+ cells on Total Therapy protocols 3a/3b (VTD-PACE) and Total Therapy 4/5 using a novel regimen that added low dose melphalan to VTD-PACE (MVTD-PACE), we analyzed mobilization and collection variables separately. A significant difference favoring MVDT-PACE was found in mean CD34+ cells/µL on day 2 of collection and in mean ratio of CD34+ cells/µL on day 2 to day 1. However, because apheresis variables and growth factor dose during collection were manipulated to optimize individual collections, the two regimens were not significantly different when the mean total CD34+ cells ×10(6) /kg collected was compared. Thus, when evaluating a chemotherapy regimen or new growth factor for mobilization, it is important to realize that total CD34+ cells collected is dependent on both mobilization and collection variables.

Harlequin ichthyosis (HI) is a rare disorder of defective lipid transport resulting in severe epidermal hyperkeratosis producing large plate-like scales. Although mortality is high, improved treatments have allowed some with HI to survive into their third and fourth decades. However, until this case, there have been no known reports of pregnancy followed by birth of a healthy neonate to a mother with HI. We report one of the only approximately 25 known current HI survivors worldwide unique in having carried a pregnancy to full term and outline challenges for the anesthesiologist during labor and delivery.

This chapter provides the engineer with a model to quantify egress performance. This model is formed from a set of numerical tools that vary in their scope and sophistication. Guidance is provided on the capabilities of these tools and on when they should be employed, making reference to the data on which these tools are based. Detailed examples are presented to clarify the application of these tools, along with a description of how the use of these tools fits in with other fire engineering calculations. This chapter will, therefore, allow the engineer to assess egress performance in a responsible and informed manner.

The SFPE Engineering Guide to Performance-Based Fire Protection [1] defines performance-based design as “an engineering approach to fire protection design based on (1) agreed upon fire safety goals and objectives, (2) deterministic and/or probabilistic analysis of fire scenarios, and (3) quantitative assessment of design alternatives against the fire safety goals and objectives using accepted engineering tools, methodologies, and performance criteria.”

The ability to predict how many CD34(+) cells a donor will collect on a given day is vital for efficient leukapheresis.We validated a formula to predict daily CD34(+) cell collections by leukapheresis, calculated as follows: (peripheral blood CD34(+) cells/L) × (adjusted collection efficiency of 30%)/body weight (kg), multiplied by the number of liters processed. This validation was performed from 234 donors undergoing 30 L large volume leukapheresis (LVL) and 162 donors undergoing smaller collections (non-LVL). The LVL group consisted of 811 collection events (625 multiple myeloma, 186 non-myeloma). The non-LVL group consisted of 224 collection events (196 multiple myeloma, 28 non-myeloma). All predicted and observed CD34(+) cell collection numbers were plotted (predicted versus observed) and assessed using linear regression analyses. Linear correlation coefficients (r-values), slopes and intercepts of the regression lines were evaluated.Predicted versus observed data points across all quantities of CD34(+) cells/kg collected by both LVL and non-LVL had strong r-values of 0.947 and 0.913, respectively, demonstrating near perfect positive linear correlations. Data for LVL collections subgrouped by number of cells collected (poor, intermediate and good), mobilization regimen, collection day and diagnosis were analyzed the same way and showed consistent findings.We have validated a formula with a strong ability to predict collection of CD34(+) cells/kg that would allow for individualization of collection for any donor once the peripheral blood CD34(+) cell count and optimal goal of collection were known; to date this has not been published by other groups.

Background Molecular-based automated systems for the rapid diagnosis of bacterial infections have potential to improve patient care. The Accelerate Pheno™ blood culture detection system (ACCEL) is an FDA approved platform that allows for identification (ID) and antimicrobial susceptibility testing (AST) 8 hours following growth in routine culture. Methods This is a single-center retrospective chart review of bacteremic adult inpatients before and after implementation of ACCEL. Laboratory and clinical data were collected February–March 2018 (intervention) and compared with a January–April 2017 historical cohort (standard of care). Standard of care ID and AST were performed using VITEK® MS (MALDI-TOF MS) and VITEK®2, respectively. An active antimicrobial stewardship program was in place during both study periods. Patients with polymicrobial cultures, off-panel isolates, previous positive culture, or who were discharged prior to final AST report were excluded. Primary outcome was length of stay (LOS). Secondary outcomes were inpatient antibiotic duration of therapy (DOT) and time to optimal therapy (TTOT). Nonparametric unadjusted analyses were performed due to non-normal distributions. Statistics were performed using SAS 9.4. Results Of the 143 positive cultures performed on ACCEL during intervention, 118 (83%) were identified as on-panel organisms. Seventy-five (64%) of these 118 cultures and 79 (70%) of 113 reviewed standard of care cultures met inclusion criteria. Patient comorbidities (P = NS), MEWS severity score (P = 0.10), source of bacteremia (P = NS), and pathogen detected (P = 0.30) were similar between cohorts. Time from collection to ID (28.2 ± 12.7 hours vs. 53.8 ± 20.9 hours; P < 0.001) and AST (31.9 ± 11 hours vs. 71.8 ± 20 hours; P < 0.001) were shorter in the intervention arm. Conclusion Compared with standard of care, ACCEL shortens laboratory turn-around-time and improves clinical outcomes. The use of this system has resulted in decreased mean antibiotic DOT, TTOT, and LOS. Further studies are needed to verify these findings. Disclosures All authors: No reported disclosures.

Post-traumatic endophthalmitis (PTE) is an uncommon sequela of open globe injuries. In cases involving an intraocular foreign body (IOFB), the risk of PTE increases by up to four-fold. Typically, presentation occurs in the acute timeframe. Only three reported cases of delayed-onset PTE currently exist in the literature (two cases caused by Proprionibacterium acnes and one by Phaeoacremonium parasiticum, a fungal pathogen). We describe a case of delayed-onset post-traumatic endophthalmitis (PTE) caused by Lysinibacillus spp., an organism not previously reported in the ophthalmic literature.

A 65-year-old female with a history of multiple tick bites presented with fever and pancytopenia. Intracytoplasmic rickettsial morulae were detected on peripheral smear and bone marrow biopsy specimens, and PCR amplified Ehrlichia ewingii DNA from both specimens. To our knowledge, this is the first report of E. ewingii infection of human bone marrow.

Thrombotic thrombocytopenic purpura (TTP) results from a congenital or acquired deficiency of the von Willebrand factor (vWF)-cleaving protease ADAMTS13. The disease can be fatal and hence treatment should be initiated promptly. Therapeutic plasma exchange (TPE) remains the standard treatment along with adjunct therapies including steroids and immunosuppressive drugs. Addition of rituximab to TPE has been shown to be beneficial in refractory/relapsing TTP; however, TPE results in removal of rituximab from the circulation requiring more frequent dosing of rituximab to achieve a favorable outcome. The intermediate-purity plasma-derived Factor VIII concentrate (FVIII) Koate® contains the highest amount of ADAMTS13 activity yet reported and has been used successfully in treating congenital TTP. Here we report our experience with addition of this FVIII concentrate to rituximab, corticosteroids and TPE in three TTP patients with an ADAMTS13 inhibitor to permit withholding TPE for 48 h after rituximab infusion.

Collection of hematopoietic progenitor cells (HPC) after previous autologous hematopoietic progenitor cell transplant (aHCT) was studied in 221 patients with multiple myeloma (MM). With a total of 333 collections, the median number of CD34+ cells collected was 4.7 × 10(6) CD34+ cells/kg, and 74% of the patients collected ≥ 2.5 × 10(6) CD34+ cells/kg. Among 26 variables examined, the strongest predictor for poor collection was a platelet count

Mobilization regimens for CD34+ cells have generally been judged successful based on the number of cells collected without evaluating mobilization separately from collection. Using retrospective data for patients who collected CD34+ cells on Total Therapy protocols 3a/3b (VTD-PACE) and Total Therapy 4/5 using a novel regimen that added low dose melphalan to VTD-PACE (MVTD-PACE), we analyzed mobilization and collection variables separately. A significant difference favoring MVDT-PACE was found in mean CD34+ cells/µL on day 2 of collection and in mean ratio of CD34+ cells/µL on day 2 to day 1. However, because apheresis variables and growth factor dose during collection were manipulated to optimize individual collections, the two regimens were not significantly different when the mean total CD34+ cells ×10(6) /kg collected was compared. Thus, when evaluating a chemotherapy regimen or new growth factor for mobilization, it is important to realize that total CD34+ cells collected is dependent on both mobilization and collection variables.

Introduction: Presence of advanced OL was recently reported as a risk for poor mobilization in patients with multiple myeloma who had poor HPC collections (Jung et al. J Clin Apheresis 2014; Apr 25. doi: 10.1002). We sought to confirm this finding and also whether poor collection correlated with low peripheral blood CD34+ cell numbers as evaluated by flow cytometry. Patients and Methods: Patients: We performed a retrospective study of patients who underwent autologous HPC collection at our institution between 2005 and 2012 to identify poor mobilizers and mega-mobilizers in a 2:1 ratio for data analysis. We defined poor mobilizers as those who required maximal plerixafor support (4 days) for collection, and mega-mobilizers as those who collected >30 x 106 CD34+ cells/kg in 2 days. We found 79 poor mobilizers, but removed 9 from data analysis because the collection variables of plerixafor timing and G-CSF dose differed from the others, leaving 64 myeloma (MM) and 6 non-myeloma plasma cell dyscrasias (NMPCD) patients for analysis: 41 male, 29 female, age range 43–86 (median 67.5). There were 37 mega-mobilizers: 36 MM, 1 NMPCD: 21 male, 16 female, age range 40–73 (median 61). Cumulative CD34+ cells/kg during leukapheresis and peak peripheral CD34+ cell counts were recorded. Apheresis: Apheresis was initiated using a central venous catheter when the predicted CD34+ cell collection for 30 L of blood processed was at least 1 x 106/kg using a predictive formula (Rosenbaum et al. Cytotherapy 2012; 14(4): 461-6). The volume of blood processed each day was based on the same predictive formula, and ranged from 5 to 30L. Cells were collected on a COBE ® Spectra apheresis machine, software version 7.0, using 1000 mL anticoagulant citrate dextrose (ACD) and 5000 units heparin for anticoagulation at an inlet:anti-coagulant ratio of 31:1, and an inlet flow rate of 150 mL/min with anti-coagulant infused at 5 mL/min. The collection flow rate was set at 1.5 mL/min and 10 mL ACD was added to the component at processed volumes of 10 L, 20 L and 30 L. An infusion of 2 g calcium chloride in 250 mL normal saline (0.9% sodium chloride) ran at 85 mL/h. Flow cytometry: CD34+ cells in peripheral blood and HPC products were quantified by flow cytometry using the ISHAGE protocol. Statistics: Mean peripheral blood CD34+ cells/µL and mean CD34+ cells/kg collected were calculated separately for the mega-mobilizer + poor mobilizer combined group, mega-mobilizer and poor mobilizer groups. All patients were subcategorized into those with ≤10 and >10 OL, and means for CD34+ cells/kg collected and peripheral blood CD34+ cells/uL were compared separately between the ≤10 and >10 OL groups using two-tailed Student’s t-tests and p-values evaluated for significance. Results: For all patients combined (mega + poor mobilizers) there were no significant differences in either peripheral CD34+ cells/µL or mean total CD34+ cells/kg collected between the ≤10 and >10 OL subgroups. Mean CD34+ cells/µL peripheral blood was 276 and 250 for the ≤10 and >10 OL groups, respectively (p=0.73), with means of 27.7 and 23.6 CD34+ × 106 CD34+ cells/kg collected (p=0.41). For the mega-mobilizers there was no significant difference in mean peripheral blood CD34+ cells/µL between the OL (10) groups (722 vs. 709, respectively; p=0.92) or in total CD34+/kg collected (55.8 and 53.8, respectively; p=0.78). For the poor mobilizers there was no significant difference in mean peripheral CD34 cells/µL between the ≤10 and >10 OL groups (27 and 20, respectively; p=0.10); however, there was a statistically significant difference in total number of CD34+ cells/kg collected, 11.9 and 8.4 ×106 CD34+ cells/kg, respectively (p=0.02). Conclusion: No significant difference was seen in mobilization as judged by peripheral blood CD34+ cells/ µL in mega-mobilizers or poor separately or combined, but a difference in the total number of CD34+ cells collected was seen in poor mobilizers. We suggest this difference results from variables in collection protocols, as we have previously shown that both mobilization and collection variables impact total CD34+ cells collected by apheresis (Abuabdou et al 2013; J Clin Aph Dec 18. doi: 10.1002). Disclosures Barlogie: Celgene: Consultancy, Patents & Royalties, Research Funding; Millenium: Consultancy, Patents & Royalties, Research Funding.

Introduction: We evaluated a predictive formula for CD34+ cell yield from HPC collections at 2 institutions using different mobilization and machine parameters on the COBE® Spectra (Spectra) and Spectra Optia® (Optia) devices. Patients and Methods: Heidelberg: Data were reviewed for all 67 pts who collected autologous HPC from 2/13/14 to 7/11/14. A total of 89 collection events (n) were analyzed (50 male, 39 female). Diagnoses were myeloma (n=64) and non-myeloma (n=25). Age was 17–74 years (median 60). Mobilization was chemotherapy + G-CSF (5 µg/kg SC daily; n=82) or G-CSF (10 µg/kg SC daily, minimum 4 days; n=7) + plerixafor (240 µg/kg SC) added to G-CSF 15 h before collection in poor mobilizers (n=9). Pts were randomly assigned to collect on either Spectra (n=26) or Optia (n=63). Anticoagulant citrate dextrose (ACD) was used at an inlet:anti-coagulant ratio of 15:1 with inlet flow rate of 40–100 mL/min. A central venous line (n=6) or peripheral access (n=83) was used to process 3–4 blood volumes. UAMS: Data were reviewed for all 52 pts who collected HPC from 8/13/13 to 7/10/14. A total of 155 collection events were analyzed (90 male, 65 female). Diagnoses were myeloma (n=127) and non-myeloma (n=28). Age was 24–79 years (median 64). Mobilization used chemotherapy + G-CSF (5–8 mg/kg SC twice daily; n=116) or G-CSF (5–8 mg/kg SC twice daily; n=39) + plerixafor (240 µg/kg SC) added to G-CSF 15 h before leukapheresis in poor mobilizers (n=41). All pts had central venous lines. Spectra pts (n=133) had 5–40 L blood processed using 1,000 mL ACD and 5,000 U heparin for anticoagulation at an inlet:anti-coagulant ratio of 31:1, inlet flow rate of 150 mL/min. Collection flow rate was set at 1.5 mL/min and 10 mL ACD was added to the component at processed volumes of 10 L, 20 L and 30 L. Optia pts (n=22) had 7–23 L blood processed using ACD at a ratio of 12:1 for the first chamber, changing to 25:1 during first chamber collection phase, with a maximum inlet flow rate of 125 mL/min. Heparinized citrate was used as with the Spectra, with 3 mL of ACD without heparin added to the product bag before start of collection, and 1 mL of ACD was added for every chamber processed during the procedure after every 10 L, with an aim to keep the concentration in the product bag 10% by volume. Pts were collected randomly on Optia one day and Spectra another and if platelet count was ≥80 K/mL were given 81 mg aspirin at start of collection. Both institutions: continuous CaCl₂ infusion was used to prevent side effects of citrate for both machines, and CD34+ cells were quantified by flow cytometry using the ISHAGE protocol. Prediction of CD34+ cells collected/L blood processed was calculated using the formula: (peripheral blood CD34+ cells/µL) × (estimated collection efficiency of 30%) / body weight (kg) (Rosenbaum et al. Cytotherapy, 2012;14:461–466). Predicted CD34+ counts/kg were plotted on the x-axis against corresponding observed counts (y-axis) for all collections and the scatter plots assessed for linear relationship between predicted and observed. Linear regression analyses were performed and the linear correlation coefficients (r-values) were calculated; slope and intercepts of the regression lines were evaluated. The same analyses were performed on the following subgroups: combined data for both institutions, data for Spectra and Optia separately by institution, and Spectra and Optia data separately but combining institutions. Results: Regression analyses performed on all collection events categorized by institution demonstrated very strong linear correlations between predicted and observed values [r=0.88 (y=1.64x - 0.10) and 0.92 (y=1.14x + 0.88), Heidelberg and UAMS, respectively]. For data combined for both institutions, strong linear correlation persisted [r=0.91 (y=1.17x + 1.31); Figure]. Data categorized by machine used (Spectra vs. Optia) both within institution and combining institutional data showed consistently strong linear correlation (r-values all >0.84). Conclusions: This is the first report confirming inter-institutional reproducibility of this formula for predicting the minimum number of CD34+ cells that may be expected for a given number of liters of blood processed for an HPC collection. We also demonstrate that inter-institutional differences in mobilization regimens and collection parameters do not affect efficacy of the prediction, nor does machine type used (Spectra vs. Optia). Figure 1 Figure 1. Disclosures Wuchter: Sanofi: Honoraria; ETICHO: Consultancy, Honoraria. Hundemer:Celgene: Research Funding, Speakers Bureau; Genzyme: Research Funding. Goldschmidt:Celgene: Consultancy, Research Funding, Speakers Bureau. Ho:Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Malaria is a mosquito-borne infectious disease caused by protists of the genus Plasmodium. Malaria is widespread in tropical regions around the equator, including much of sub-Saharan Africa, Asia, and the Americas, and uncommonly seen in the developed world. Although a variety of ocular manifestations have been linked to malaria, optic neuritis is rare. We report a patient who developed bilateral optic neuritis after he was treated successfully for acute falciparum malaria.

Introduction Plerixafor has recently been reported to be associated with an increased risk for developing MDS in patients with hematologic malignancies (Deol A et al. 2013; Bone Marrow Transplant 48:1112-6). Our group has extensive experience with plerixafor and we sought to confirm this finding. Patients and Methods A total of 294 patients treated at our institution between 2003-2013 (MM: 252, NHL: 22, Hodgkin: 4, Waldenstrom macroglobulinemia: 4, Amyloidosis: 4, LCDD: 2, other: 6) were identified as having received plerixafor as part of their mobilization regimen (62% male/ 38% female, median age 63.2 years (range 26-85)). Metaphase karyotypes for all 294 patients were reviewed for cytogenetic abnormalities typical for MDS (MDS-Ca). Clinical MDS/AML was defined as the condition for which specific MDS/AML therapy was required and administered. Of these, 11 patients developed MDS-Ca or clinical MDS prior to plerixafor administration and were excluded from further evaluation. For statistical analyses we divided our group by age (60) and looked at variables our group has found to correlate with development of MDS-Ca or clinical MDS, i.e. albumin, hemoglobin, and platelet count immediately prior to mobilization and inadequate HPC collection (defined as Results Of the 283 eligible patients, 20 patients demonstrated a relevant outcome for this study (MM: 19, NHL: 1). MDS-Ca developed in 18 patients (6.4%), of whom 8 went on to develop clinical MDS/AML. Clinical MDS developed in 1 patient without prior MDS-Ca and 1 patient developed AML without any preceding cytogenetic abnormality, thus clinical MDS/AML developed in 10 patients overall (3.5%). The average time from HPC collection and plerixafor exposure to either MDS-Ca or clinical MDS/AML was 21.2 months (range 94-2268 days). None of the laboratory variables examined significantly correlated with likelihood of developing MDS-Ca or clinical MDS/AML. Inadequate collection was not associated with an increased incidence of MDS-Ca or clinical MDS/AML. Of the 283 eligible patients who were collected, 208 went on to autologous HPC transplant. Of those who were transplanted, 11 patients developed MDS-Ca (of which 4 later developed clinical MDS), 1 patient developed clinical MDS and 1 developed AML without preceding cytogenetic abnormalities. The average time from infusion of HPC to development MDS-Ca or clinical MDS/AML post-transplant was 24.2 months (range 221-2253 days). Conclusion The numbers of patients in this study who received plerixafor and developed MDS-Ca or clinical MDS/AML are comparable to recently reported rates of secondary MDS-Ca (11%) and clinical MDS/AML (3%) in patients with MM treated in our institution on our TT2/TT3 protocols (Usmani SZ Blood;121:4753-7). Further analyses to include additional variables, including collection of HPC infused at transplant before first transplant or later is currently underway. Disclosures: Usmani: Celgene: Consultancy, Research Funding, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Barlogie:Celgene: Consultancy, Honoraria, Research Funding; Myeloma Health, LLC: Patents & Royalties.

8610 Background: aHCT is a proven therapeutic modality in treating relapsed multiple myeloma (MM). However, previously transplanted patients may have no hematopoietic progenitor cells (HPC) left in storage. Methods: Collection of HPC after aHCT was studied in 221 MM patients who underwent 333 mobilization attempts between 10/2000 and 06/2012. Results: The median number of CD34+ collected was 4.7 ×106/kg, with 74% of collections yielding at least 2.5×106/kg. Mobilization with chemotherapy and G-CSF was most efficient, yielding a median of 6.84×106/kg (p6/kg (p6/kg) collection (1.83 vs. 3.43×106/kg, p6/L (p6/L was significant (p6/L (p6/L suggest the need for plerixafor for a successful collection. Infusion of the graft procured is safe and effective, but use of only cells collected after aHCT is associated with delayed platelet engraftment >50×106/L.

Abstract 3436 Platelet refractoriness or lack of platelet increase after platelet transfusion is seen in a fraction of patients who receive platelet transfusion support. Antibodies may develop against specific platelet surface proteins or be directed against HLA-Class I components resulting in the removal of the platelets from the circulation. Donor platelet crossmatching with patient serum is typically required to determine compatible platelet units, ones for which patient antibodies will not result in subsequent platelet loss following transfusion. The objective of this study was to determine if the percent calculated Panel Reactive Antibodies (cPRA) for class I HLA antigens could predict the percent of positive platelet crossmatches (XM). In this way, the blood bank could have better ability to predict the number of platelet units to set up for crossmatching, in order to find compatible units. Platelet XM were performed using the Capture-P® Immucor Gamma® and cPRA levels were determined by Luminex® assay using One Lambda® single-antigen HLA-class I beads. A retrospective review of platelet XM performed on patients at UAMS and their donors during 2008–2012 was performed. Patients who had two or more platelet XM completed were included in the study in order to reduce donor bias, due to potential reduced HLA diversity in the platelet donor pool. For each patient the mean percentage of all positive platelet XM performed was calculated. These results were compared with the corresponding mean percent cPRA levels against class I HLA antigens. Additionally, the cPRA value of each patient was compared with the subsequent most contiguous platelet XM performed. The “ideal” relationship of cPRA to platelet XM would be 1:1, and therefore a plot of % cPRA vs % XM would have a slope of one. Patient % cPRA vs % XM were plotted and the slopes compared with the ideal plot, and the correlation coefficients were calculated using Microsoft® Excel®. A total of 50 patients (37 females and 13 males) were included in the study. The mean age of these patients was 59 years (range 26–77 years). Majority of the patients (41/53) had multiple myeloma while a small number of patients had other diagnoses (aplastic anemia 2/53; diffuse large B cell lymphoma 1/53; Grade III follicular lymphoma 1/53; Multicentric Castleman's disease 1/53; multicentric Castlemans's disease with progression to large B cell lymphoma 1/53; Von Williebrand's disease type 2b 1/53; Refractory cytopenia with multilineage dysplasia and fibrosis 1/53; and cirrhosis 1/53). Of these, one patient had 111 platelet crossmatches performed and four patients had multiple cPRA levels done. The average positive platelet XM was 61% (range 0–100%) and the average cPRA level was 66% (range 0–100%). Data are presented in the Figure. Comparisons of slopes of measured data and predicted ideal data are indistinguishable, p>0.99. Therefore, the percent cPRA is predictive of the percent positive platelet XM. Thus, a higher % cPRA would predict a greater number of positive platelet XM, and thereby alert the blood bank that additional platelets units may be required for finding XM compatible platelet units. Figure: Plot of % cPRA vs % positive platelet XM reveals indistinguishable slopes (p>0.99), therefore indicating that the % cPRA is predictive of the % positive platelet XM. Figure:. Plot of % cPRA vs % positive platelet XM reveals indistinguishable slopes (p>0.99), therefore indicating that the % cPRA is predictive of the % positive platelet XM. Disclosures: No relevant conflicts of interest to declare.

Abstract 4388 Background: Many patients who are poor CD34+ cell mobilizers receive the CXCR4 inhibitor plerixafor to enhance mobilization. Here we examined whether chemotherapy followed by growth factor (GF) + plerixafor for mobilization improves CD34+ cell collection in these patients. Materials and Methods: We reviewed CD34+ cell collection data from January 2009 through June 2011 for all patients (n=152) at our institution who received plerixafor with GF ± chemotherapy. The primary disease in both groups was multiple myeloma, with 14 non-myeloma patients in the chemotherapy group and 8 non-myeloma patients in the no-chemotherapy group. There were 82 collections preceded by mobilization with chemotherapy (53 male, 29 female), and 80 collections without chemotherapy (51 male, 29 female). Several patients collected on more than one occasion. Age range in the chemotherapy group was 36–76y (median 64) and in the no-chemotherapy group was 42–83y (median 63). Our standard protocol is to collect with plerixafor for 4 consecutive days using a large volume leukapheresis (30L processed). Of the total 162 collections, CD34+ cells collected on each of the 4 consecutive days were recorded. If during the collection process a day was skipped, if less than 4 days of collection were performed, or a collection event on a particular day processed any blood volume other than 30L, all days including and subsequent to such events were excluded from analyses. CD34+ cells were quantified by flow cytometry. Mean CD34+ cells collected on days 1–4 were recorded separately for both groups and compared using two-tailed student’s t-tests. Results: Mean number of CD34+ cells collected for the chemotherapy group on days 1–4 were 2.65 (n=82), 2.27 (n=69), 1.60 (n=47), and 1.25 × 106 CD34+ cells/kg (n=38), respectively. Mean number of CD34+ cells collected for the no-chemotherapy group on days 1–4 were 2.51 (n=80), 1.83 (n=67), 1.22 (n=45), and 0.97 × 106 CD34+ cells/kg (n=28), respectively. There were no statistically significant differences between mean CD34+ cells collected on days 1–4 between the two groups (all p-values >0.05). We also asked whether the decrease in mean CD34+ cell yield observed as collection progressed was statistically significant. This phenomenon was determined significant (by one-way ANOVA) for both the chemotherapy and no-chemotherapy groups tested separately (p-values 0.02 and 0.003, respectively). Conclusions: Chemotherapy plus GF and plerixafor does not improve CD34+ cell collection in poor mobilizers compared to GF+plerixafor alone. Additionally, mean number of CD34+ cells collected decreases each day, regardless of which of the two mobilization regimens is used. Disclosures: Pesek: Genzyme: Membership on an entity’s Board of Directors or advisory committees. Cottler-Fox:Genzyme: Membership on an entity’s Board of Directors or advisory committees.

Abstract 1182 Background: The ability to predict the number of CD34+ cells a patient will collect after mobilization is vital to efficient apheresis. It is common to quantify circulating blood CD34+ cells/μL prior to collection. Cut off values for initiating collection based on this number are usually based on experience at each center. We developed a formula for predicting CD34+ cell collection based on specific laboratory values and constants. Materials and Methods: Data were reviewed for all 234 patients who collected CD34+ cells at our institution from 7/1/09 to 6/30/10 using a large volume (30 L processed) leukapheresis on a COBE® Spectra. Predicted numbers of CD34+ cells collected/L blood processed were calculated based on the following formula: (peripheral blood CD34+ cells/μL) × (estimated collection efficiency of 30%) / body weight (kg). The value obtained is multiplied by 30 to predict collection for a processed volume of 30 L. For the 234 patients, a total of 811 collection events were analyzed. The 811 collection events included 526 male and 285 female collections. Multiple myeloma was the diagnosis for 625 collection events, with 186 collections obtained from non-myeloma patients. Age ranged from 21 to 84 years (median 62). The CD34+ cells collected were quantified by flow cytometry using the ISHAGE protocol on a FACSCalibur™ instrument. All 811 predicted CD34+ counts were plotted on the x-axis against their corresponding observed counts (y-axis) and the scatter plot was assessed for a linear relationship between predicted and observed. A linear regression analysis was performed and the linear correlation coefficient (r-value) was calculated. The slope and intercepts of the regression line were evaluated. Observed collection events were also subcategorized into three groups: “good” mobilizers (>10×106 CD34+ cells/kg; n=91 collection events), “slow” mobilizers (>2 to ≤10×106 CD34+ cells/kg; n=335 events), and “poor” mobilizers (≤2×106 CD34+ cells/kg; n=385 events). The same analyses were performed on these subgroups. Results: Predicted versus observed data points across all quantities of CD34+ cells collected had a strong r-value of 0.947 demonstrating near perfect linear correlation. The equation of the line was y=1.15x+0.25, indicating that the model consistently slightly underpredicts the number of CD34+ cells/kg obtained at collection. The same data subcategorized by type of mobilizer (good, slow, and poor), confirmed linear relationships even over these narrower collection spans, still with relatively good r-values of 0.848, 0.777, and 0.703, respectively. The unique regression line for poor mobilizers revealed that at extremely low predicted collections (e.g. 0.05×106 CD34+ cells/kg) the formula underpredicts, however as one approaches 2×106 CD34+ cells/kg, the formula more closely predicts the number of cells collected (y=0.72x+0.35). For slow mobilizers, the formula consistently predicts over the entire range the observed number of CD34+/kg collected (y=0.68x+1.91). Finally, the individual regression line for good mobilizers revealed a consistent slight underprediction over the entire range (y=0.95x+4.45). Results: Our formula shows a strong ability to predict CD34+ cell/kg collection for all types of mobilizers. Clinical benefits of this formula include knowing how many days a patient may need to collect to acquire a certain number of cells. Laboratory benefits include providing advance estimates of how many collection bags will be needed for a patient, how much freeze mix to prepare, and how many cassettes to prepare for storage. Finally, a predictive formula can play an important role in quality control of apheresis. Disclosures: No relevant conflicts of interest to declare.

Abstract 4051 Introduction: What constitutes an acceptable mobilization regimen for collecting CD34+ cells depends on whether the goal of collection is to obtain a minimum number versus optimal number of cells. When treating patients with high-risk myeloma it may be important to obtain an optimal number. Here we compare retrospectively our earlier mobilization regimen, VTD-PACE, with MVTD-PACE in newly diagnosed, previously untreated multiple myeloma patients. Materials and Methods : We reviewed data for all patients who collected hematopoietic progenitor cells on Total Therapy protocols TT3a/TT3b with VTD-PACE (n=394) from February 2004 to September 2008 (138 females and 256 males, median age 59y; range 31–75), and on TT4/TT5 with MVTD-PACE (n=188) from August 2008 to May 2011 (78 females and 110 males, median age 61y, range 30–76). Based on their predicted first day collection with a large volume leukapheresis (30L processed), using our center's predictive formula (Blood 2010; 116(21):1182a), patients were stratified into 4 mobilizer types: poor (10 to 20×106) and excellent (>20×106). Variables examined included number of CD34+ cells/μl blood on day 1 and day 2 of collection (we have a minimum 2 day collection requirement), number of collection days to reach our minimum goal of 20×106 CD34+ cells/kg, and total CD34+ cells/kg collected for both chemotherapy groups. Variables for both groups stratified by mobilizer type were compared using two-tailed student's t-tests, except for the poor mobilizer group, where population size was too small for formal statistical analyses (VTD-PACE n=7, MVTD-PACE n=4), although averages were calculated. Results : There was no significant difference between VTD-PACE and MVTD-PACE for CD34+ cells/μl blood on day 1 of collection among the excellent [mean 368.9 (n=184) vs. 434.6 x106 (n=92); p-value 0.07], good [mean 138.6 (n=102) vs. 128.6 x106 (n=40); p-value 0.19], and intermediate [mean 60.1 (n=100) vs. 55.9 x106 (n=52); p-value 0.39] groups. A statistically significant difference between VTD-PACE and MVTD-PACE was found for CD34+ cells/μl blood on day 2 of collection for excellent mobilizers [mean 333.8 (n=184) vs. 460 ×106 (n=92); p-value Disclosures: No relevant conflicts of interest to declare.