Automated Good Manufacturing Practice-compliant generation of human monocyte-derived dendritic cells from a complete apheresis product using a hollow-fiber bioreactor system overcomes a major hurdle in the manufacture of dendritic cells for cancer vaccines.

BACKGROUND: Although dendritic cell (DC)-based cancer vaccines represent a promising treatment strategy, its exploration in the clinic is hampered due to the need for Good Manufacturing Practice (GMP) facilities and associated trained staff for the generation of large numbers of DCs. The Quantum bioreactor system offered by Terumo BCT represents a hollow-fiber platform integrating GMP-compliant manufacturing steps in a closed system for automated cultivation of cellular products. In the respective established protocols, the hollow fibers are coated with fibronectin and trypsin is used to harvest the final cell product, which in the case of DCs allows processing of only one tenth of an apheresis product. MATERIALS AND RESULTS: We successfully developed a new protocol that circumvents the need for fibronectin coating and trypsin digestion, and makes the Quantum bioreactor system now suitable for generating large numbers of mature human monocyte-derived DCs (Mo-DCs) by processing a complete apheresis product at once. To achieve that, it needed a step-by-step optimization of DC-differentiation, e.g., the varying of media exchange rates and cytokine concentration until the total yield (% of input CD14+ monocytes), as well as the phenotype and functionality of mature Mo-DCs, became equivalent to those generated by our established standard production of Mo-DCs in cell culture bags. CONCLUSIONS: By using this new protocol for the Food and Drug Administration-approved Quantum system, it is now possible for the first time to process one complete apheresis to automatically generate large numbers of human Mo-DCs, making it much more feasible to exploit the potential of individualized DC-based immunotherapy.

Safety and efficacy of autologous mononuclear cell and stem cell apheresis in very low-weight children-Experience at a single center.

BACKGROUND: Apheresis in children with low body weight is technically limited by their tolerance of the extracorporeal blood volume. STUDY DESIGN AND METHODS: This paper presents a single-center experience with 23 procedures in 12 children with weights between 5.2 and 9.5 kg using the Spectra Optia mononuclear cell (MNC) protocol with blood priming. RESULTS: The average procedure duration was 158 minutes, and the median processed blood volume was 316 mL/kg. The white blood cell (WBC), platelet (PLT), and hemoglobin (HGB) values showed a downward trend with increased volume of processed blood. The post-apheresis HGB concentration was increased in all procedures due to initial priming with packed red blood cells (PRBCs), but this effect disappeared at a level of ~400 mL of processed blood/kg. The median volume of the cellular product was 36 mL, the WBC count was 153 K/µL, the hematocrit (HCT) was 1.5%, the PLT count was 602 K/µL, the WBC collection efficacy (CE2) was 13.2%, and the PLT CE2 was 9.5%. The median CD34+ CE2 was 28%, and interpolation of the CD34+ CE2 yielded a Y-intercept value of 32%. Higher pre-collection CD34+ counts resulted in higher CD34+ yields. No correlation was found between the pre-collection CD34+ results and CD34+ CE2. CONCLUSION: The analyzed data demonstrated the feasibility and safety of apheresis in very low-weight children. The laboratory abnormalities were asymptomatic and citrate toxicity was mild. Visual control of clogging with manual adjustment of the citrate infusion rate is important to reduce exposure to citrate.

Audits of collection and apheresis centers: guidelines by the World Marrow Donor Association Working Group Quality and Regulation.

According to the Standards of the World Marrow Donor Association (WMDA), unrelated stem cell donor registries and donor centers are responsible for compliance of their collection and apheresis centers with these Standards. To ensure high stem cell product quality and high standards for safety and satisfaction of voluntary unrelated stem cell donors, we here present guidelines for audits of collection and apheresis centers that can be used by new and established donor registries, as well as by collection centers in preparation of audits. We define the general requirements and recommendations for collaboration with the collection and apheresis centers and define critical procedures for the collection of the stem cell product, such as information session, medical assessment, product collection, quality controls, product handover for transportation, and donor follow-up. The specific guidelines are accompanied by detailed checklists and forms that can be found in Supplementary Information and may be used during an initial or follow-up on-site or paper-based audit.

Change of apheresis device decreased the incidence of severe acute graft-versus-host disease among patients after allogeneic stem cell transplantation with sibling donors.

BACKGROUND: The composition of the graft used for allogeneic hematopoietic stem cell transplantation (HSCT) is important for the treatment outcome. Different apheresis devices may yield significant differences in peripheral blood stem cell graft cellular composition. We compared stem cell grafts produced by Cobe Spectra (Cobe) and Spectra Optia (Optia) with use of the mononuclear cell (MNC) protocol, and evaluated clinical outcome parameters such as graft-versus-host disease (GvHD), transplant-related mortality (TRM), relapse, and overall survival. STUDY DESIGN AND METHODS: During 5 years, 31 Cobe Spectra and 40 Spectra Optia grafts were analyzed for CD34, CD3, CD4, CD8, CD19, and CD56 cell content. Clinical outcome parameters were correlated and compared between the two patient groups using different apheresis devices. RESULTS: Optia grafts contained fewer lymphocytes compared to Cobe (p < 0.001). Optia grafts had a significantly lower incidence of acute GvHD Grades II through IV (Cobe 45% vs. Optia 23%; p = 0.039) and TRM (16% vs. 2.5%; p < 0.05) but higher chronic GvHD (32% vs. 67%; p = 0.005) compared to Cobe grafts. Finally, the multivariate analysis showed a significant correlation among the different apheresis devices and both acute GvHD II through IV and severe chronic GvHD. The multivariate analysis also showed a significant correlation between the CD3+ cell dose and the incidence of severe acute GvHD. CONCLUSION: Optia-obtained grafts yielded a lower acute GvHD Grades II-IV and TRM risk, but had no impact on relapse or overall survival in this study. Understanding and further improvement of peripheral blood stem cell (PBSC) apheresis techniques may be used in the future to personalize HSCT by, for example, fine-tuning the GvHD incidence.

Impact of apheresis automation on procedure quality and predictability of CD34+ cell yield.

Success of peripheral blood stem cell (PBSC) collections depends on patient biological parameters and stable apheresis device performance. We investigated product quality and factors influencing main apheresis procedure outcomes including CD34+ collection efficiency (CE), product volume or platelet CE. We also assessed different CD34+ cell yield prediction algorithms. Autologous PBSC collections by Spectra Optia from myeloma and lymphoma patients were analyzed. Complete blood count (CBC) from patient preprocedure and from collected products were assessed. (1) Product yield was calculated, (2) Product CBC was correlated with patient preprocedure variables, and (3) Predictions of CD34+ yields based on (a) product CD34+ cell concentration in samples after two or four chamber flushes or (b) traditional CE2 benchmark, were compared. 62 procedures in 41 patients were analyzed. 84% of all procedures were run without operator intervention. Median CD34+ CE2 was 56.9% (48.8%-65.2%) and quite stable irrespective of patient conditions, with minor influence from patient white blood cell (WBC) precounts (rs  = -.47; P < .001). Platelet loss correlated with WBC precount (rs  = .46; P < .001), product volume (rs  = .71; P < .0001) and number of chambers collected (rs  = .72; P < .0001). CD34+ cell yield was better predicted based on (a) product CD34+ cell concentration from samples after 2 and 4 chamber flushes, respectively (rs  = .969; P < .0001 and rs  = .9648; P < .0001) than based on (b) CE2 formula (rs  = .8262, P < .0001). Spectra Optia provides good quality PBSC products with stable and predictable yield regardless of starting conditions. CD34+ sampling of product after few chamber flushes could be used to predict CD34+ yield.

Higher Donor Apheresis Blood Volumes Are Associated with Reduced Relapse Risk and Improved Survival in Reduced-Intensity Allogeneic Transplantations with Unrelated Donors.

Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning (RIC) offers a curative option for patients with hematologic malignancies who are unable to undergo myeloablative conditioning, but its success is limited by high rates of relapse. Several studies have suggested a role for T cell doses in peripheral blood stem cell grafts in RIC HSCT. Because T cell dose is typically not known until after the collection, and apheresis blood volume is easily modifiable, we hypothesized that higher donor apheresis blood volumes would improve transplantation outcomes through an effect on graft composition. Thus, we analyzed the relationships between apheresis volume, graft composition, and transplantation outcomes in 142 consecutive patients undergoing unrelated donor allogeneic RIC HSCT. We found that apheresis volume ≥15 L was associated with a significantly decreased risk of relapse (adjusted hazard ratio [aHR], .48; 95% confidence interval [CI], .28 to .84]; P = .01) and improved relapse-free survival (aHR, .56; 95% CI, .35 to .89; P = .02) and overall survival (aHR, .55; 95% CI, .34 to .91; P = .02). A high apheresis volume was not associated with increased rates of acute or chronic graft-versus-host disease. These results demonstrate that an apheresis volume of at least 15 L is independently predictive of improved transplantation outcomes after RIC allogeneic HSCT.

Manufacture of Autologous CD34+ Selected Grafts in the NIAID-Sponsored HALT-MS and SCOT Multicenter Clinical Trials for Autoimmune Diseases.

To ensure comparable grafts for autologous hematopoietic cell transplantation (HCT) in the National Institute of Allergy and Infectious Diseases-sponsored Investigational New Drug protocols for multiple sclerosis (HALT-MS) and systemic sclerosis (SCOT), a Drug Master File approach to control manufacture was implemented, including a common Master Production Batch Record and site-specific standard operating procedures with "Critical Elements." We assessed comparability of flow cytometry and controlled rate cryopreservation among sites and stability of cryopreserved grafts using hematopoietic progenitor cells (HPCs) from healthy donors. Hematopoietic Progenitor Cells, Apheresis-CD34+ Enriched, for Autologous Use (Auto-CD34+HPC) graft specifications included ≥70% viable CD34+ cells before cryopreservation. For the 2 protocols, 110 apheresis collections were performed; 121 lots of Auto-CD34+HPC were cryopreserved, and 107 of these (88.4%) met release criteria. Grafts were infused at a median of 25 days (range, 17 to 68) post-apheresis for HALT-MS (n = 24), and 25 days (range, 14 to 78) for SCOT (n = 33). Subjects received precryopreservation doses of a median 5.1 × 106 viable CD34+ cells/kg (range, 3.9 to 12.8) for HALT-MS and 5.6 × 106 viable CD34+ cells/kg (range, 2.6 to 10.2) for SCOT. Recovery of granulocytes occurred at a median of 11 days (range, 9 to 15) post-HCT for HALT-MS and 10 days (range, 8 to 12) for SCOT, independent of CD34+ cell dose. Subjects received their last platelet transfusion at a median of 9 days (range, 6 to 16) for HALT-MS and 8 days (range, 6 to 23) for SCOT; higher CD34+/kg doses were associated with faster platelet recovery. Stability testing of cryopreserved healthy donor CD34+ HPCs over 6 months of vapor phase liquid nitrogen storage demonstrated consistent 69% to 73% recovery of viable CD34+ cells. Manufacturing of Auto-CD34+HPC for the HALT-MS and SCOT protocols was comparable across all sites and supportive for timely recovery of granulocytes and platelets.

Multicenter study to evaluate a new enumeration method for hematopoietic stem cell collection management.

BACKGROUND: CD34 flow cytometry is the gold standard for stem cell enumeration in peripheral blood at the mobilization stage and in the final apheresis product. The new stem cell mode of the Sysmex XN Series analyzer enumerates an immature cell population in the white progenitor and pathological cell (WPC) channel, based on the cell size, internal cellular complexity, and fluorescence intensity. STUDY DESIGN AND METHODS: In this multicenter study we analyzed 147 peripheral blood samples, 22 samples during collection of stem cells, and 45 samples from the apheresis product of 18 healthy allogeneic donors and 84 autologous patients. RESULTS: In this multicenter study we demonstrate that the XN stem cell enumeration method correlates well with viable CD34+ cells determined by flow cytometry during the stem cell mobilization phase to determine apheresis start time, during apheresis for real-time monitoring and adjustment, and for quality control of the final stem cell harvest. CONCLUSION: Our data show that there is an improvement in the correlation of XN stem cells and CD34+ cells in the peripheral blood during stem cell mobilization as well as in stem cell harvests compared to SE or XE Series analyzers. The XN stem cell enumeration method has a number of advantages compared to CD34 flow cytometry: it is fast, simple, reproducible, and less expensive. CE marking for the European market has been obtained, making the stem cell count on the XN analyzer a reportable clinical variable.

Barriers to the Implementation of Lipoprotein Apheresis in Canada.

This article details the effectiveness of using lipoprotein apheresis (LA) rather than plasmapheresis in patients with homozygous familial hypercholesterolemia (HoFH), using results from the first HoFH pediatric patient treated with LA in Ontario. We further detail the barriers involved in adhering to international guidelines by implementing this as a first-line treatment for this condition in Ontario, and the potential savings that would be gained with treating the remaining HoFH patients in this province with LA. A primary barrier has been the division of responsibility that exists in Canada, where the delivery of medical services and the delivery of blood products are separated, artificially discounting the price of plasmapheresis and making it seem like the less expensive option. We would like to implement LA as a first-line therapy, to not only improve patient quality of life and outcomes, but to also to potentially save our federal and provincial governments' taxpayer money.

Apheresis for collection of Ebola convalescent plasma in Liberia.

PURPOSE: This report describes initiation of apheresis capability in Liberia, Africa to support a clinical trial of convalescent plasma therapy for Ebola Virus Disease. METHODS: A bloodmobile was outfitted in the United States as a four-bed apheresis unit with capabilities including pathogen reduction, electronic blood establishment computer system, designated areas for donor counseling and laboratory testing, and onboard electrical power generation. After air transport to Liberia, the bloodmobile was positioned at ELWA Hospital, Monrovia, and connected to the hospital's power grid. Liberian staff were trained to conduct donor screening, which included questionnaire and onsite blood typing and transfusion transmitted infection (TTI) testing, and plasma collection and processing. RESULTS: The bloodmobile was operational within 3 weeks after arrival of the advance team. Of 101 donors who passed the pre-screening questionnaire, 32 were deferred. Twenty-eight of ninty-nine tested survivors were deferred for positive transfusion transmitted infection (TTI) tests; twenty-one were positive for hepatitis B, hepatitis C, or human immunodeficiency virus. The majority of donors had type O blood; all but one were Rh positive. Forty-three survivors donated at least once; eighty-nine apheresis attempts resulted in eighty-one successful collections. CONCLUSIONS: Apheresis capability was emergently established in Liberia to support an efficacy trial of Ebola Convalescent Plasma. Extensive cooperation among multinational team members, engineers, logisticians, and blood safety technical personnel at the operational site was required to surmount challenges to execution posed by logistical factors. The high proportion of positive TTI tests supported the use of a pathogen reduction system to enhance product safety. J. Clin. Apheresis 32:175-181, 2017. © 2016 Wiley Periodicals, Inc.

Prospective randomized and crossover comparison of two apheresis machines for peripheral blood stem cell collection: a multicenter study.

BACKGROUND: Improving apheresis technology may lead to an efficient and safe peripheral blood stem cell (PBSC) collection. Recently, the Spectra Optia (Optia, Terumo BCT) was introduced as an automated apheresis instrument, but comparisons with other instruments have been few. This is the first randomized multicenter and crossover comparison of the Optia with the automated program of the established apheresis instrument, the Spectra (Spectra-Auto, Terumo BCT). STUDY DESIGN AND METHODS: A total of 233 apheresis procedures performed in 46 autologous patients and 108 allogeneic donors were investigated. Apheresis performed in the first day for all subjects using the Spectra-Auto (n = 79) and the Optia (n = 75) were evaluated as first-day analysis. Seventy-nine subjects, who required another session on the second day, underwent apheresis using the other instrument than the first-day instrument and were compared with each other in a paired crossover analysis. RESULTS: The two instruments processed similar volumes with comparable run times and volumes of acid-citrate-dextrose used. The volumes of collected products were greater in the Optia. Yields of mononuclear cells and CD34+ cells were not different, but collection efficiencies were higher in the Optia (p = 0.008 in CE1 of crossover analysis). Spectra-Auto-collected products contained more contaminating red blood cells (RBCs), whereas there was a trend of more contaminating platelets (PLTs) in the Optia-collected products. Slight reductions were noted in the RBC or PLT counts of subjects who underwent apheresis with the Spectra-Auto or the Optia, respectively. CONCLUSION: The Optia is safe and more efficient in the PBSC collection compared with the Spectra-Auto.

Comparison of two apheresis systems during hematopoietic progenitor stem cell collections at a tertiary medical center.

BACKGROUND: The Spectra Optia is a newer apheresis system developed based on the COBE Spectra platform. COBE Spectra requires more manual control, while Spectra Optia offers greater automation. The purpose of this study was to compare the two systems during hematopoietic progenitor stem cell (HPSC) collections. STUDY DESIGN AND METHODS: A retrospective review of 41 collections performed in 26 subjects at a tertiary medical center between June 1, 2013, and December 31, 2013, was conducted, 11 with the Spectra Optia and 30 with the COBE Spectra. Six patients underwent two consecutive daily collections, first on the Spectra Optia followed by the COBE Spectra. RESULTS: Procedure run time with the Spectra Optia was considerably longer than with the COBE Spectra (283 ± 11 min vs. 217 ± 2 min, respectively; p < 0.01). Mean CD34+ cell yields with the Spectra Optia were comparable with those of the COBE Spectra. Products collected with the Spectra Optia had less red blood cell contamination. However, platelet (PLT) attrition was greater with the Spectra Optia. Similar results were obtained in patients who were collected on consecutive days in both systems. CONCLUSION: Collections with the Spectra Optia take longer and lead to greater PLT losses during HPSC collections.

Course of iron parameters in HFE-hemochromatosis patients during initial treatment with erythrocytapheresis compared to phlebotomy.

Current treatment for newly diagnosed patients with hereditary hemochromatosis (HH) and iron overload consist of weekly phlebotomy or less frequent and more personalized erythrocytapheresis. Previous observations during phlebotomy suggest an increase in intestinal iron uptake caused by lowering of hepcidin as a result of intensive bloodletting. It is not known whether such an effect is present or even more pronounced using erythrocytapheresis since a larger amount of iron is extracted per procedure. In this study we aimed to assess the effect of erythrocytapheresis on the course of iron parameters, with special focus on serum hepcidin. We performed a retrospective proof-of-principle observational study, comparing serum iron parameters in 12 males during the depletion phase using either phlebotomy (n = 6) or erythrocytapheresis (n = 6). Decreases in serum ferritin over time were similar for both treatments but more pronounced using erythrocytapheresis when expressed per treatment procedure. Hemoglobin did not change during erythrocytapheresis, whereas during phlebotomy decreased with 10%. Increase of erythropoietin and soluble transferrin receptor and decrease in transferrin saturation were similar for both treatments. Reduction in serum hepcidin was higher (50% versus 25% of initial value) and occurred more early using phlebotomy (10 versus 20 weeks after start). In aggregate, compared to phlebotomy, the less frequent and more personalized erythrocytapheresis leads to a more pronounced decrease in serum ferritin per treatment procedure, without a larger decrease in serum hepcidin. This may be clinically relevant and may prevent an increase in intestinal iron uptake and an ensuing vicious circle of more frequent treatment procedures. J. Clin. Apheresis 31:564-570, 2016. © 2015 Wiley Periodicals, Inc.

Comparison of two low-density lipoprotein apheresis systems in patients with homozygous familial hypercholesterolemia.

Low-density lipoprotein (LDL) apheresis (LA) is a reliable method to decrease LDL-C concentrations and remains the gold standard therapy in homozygous familial hypercholesterolemia (HoFH). The objective of this study was to compare the efficacy of two LA systems [heparin-induced extracorporeal LDL precipitation (HELP) vs. dextran sulfate adsorption (DS) on the reduction of lipids, inflammatory markers, and adhesion molecules in a sample of genetically defined HoFH subjects (n = 9)]. Fasting blood samples were collected before and after LA. All subjects served as their own control and were first treated with the HELP system then with DS in this single sequence study. Compared with HELP, DS led to significantly greater reductions in total cholesterol (-63.3% vs. -59.9%; P = 0.05), LDL-C (-70.5% vs. -63.0%; P = 0.02), CRP (-75.3% vs. -48.8%; P < 0.0001), and TNF-α (-23.7% vs. +14.7%; P = 0.003). Reductions in the plasma levels of PCSK9 (-45.3% vs. -63.4%; P = 0.31), lipoprotein (a) (-70.6% vs. -65.0%; P = 0.30), E-selectin (-16.6% vs. -18.3%; P = 0.65), ICAM-1 (-4.0 vs. 5.6%; P = 0.56), and VCAM-1 (8.3% vs. -1.8%; P = 0.08) were not different between the two systems. For the same volume of filtered plasma (3,000 mL), however, HELP led to greater reductions in plasma apoB (-63.1% vs. -58.3%; P = 0.04), HDL-C (-20.6% vs. -6.5%; P = 0.003), and PCSK9 (-63.4% vs. -28.5%; P = 0.02) levels. These results suggest that both LA systems are effective in reducing plasma lipids and inflammatory markers in HoFH. Compared with HELP, greater reductions in lipid levels and inflammatory markers were achieved with DS, most likely because this method allows for a larger plasma volume to be filtered. J. Clin. Apheresis 31:359-367, 2016. © 2015 Wiley Periodicals, Inc.

Lipoprotein apheresis reduces circulating galectin-3 in humans.

BACKGROUND: Plasma galectin-3 (Gal-3) is elevated in, and drives, diverse systemic inflammatory disorders, including cancer, cardiovascular diseases, and diabetes. Circulating Gal-3 promotes tumorigenesis and metastasis, as well as fibrotic remodeling, and is a promising therapeutic target. Apheresis has proven utility in reducing circulating disease-promoting substances, exemplified by the success of lipoprotein apheresis (LA) in abrogating cardiovascular disease progression in drug-refractory hypercholesterolemia patients. We compared the clinical utility of two FDA-approved LA systems in reducing plasma Gal-3 in humans. METHODS: Plasma Gal-3 levels were assessed by ELISA in blinded samples drawn pre- and post-apheresis from hypercholesterolemia patients (n = 10/group) undergoing therapeutic LA using either a heparin-induced extracorporeal LDL precipitation (HELP) or dextran sulfate-adsorption (DSA) system. RESULTS: Mean baseline plasma Gal-3 concentrations (±SD) were 14.3 ± 5.1 (range 6.6-22.8) and 14.5 ± 2.8 (range 10.6-19.8) ng/mL in the HELP and DSA groups, respectively. Post-apheresis Gal-3 levels were respectively reduced by 19.4% and 22.7% in the HELP (P = 0.0094) and DSA (P = 0.0027) systems (paired t-tests); the difference between devices was insignificant (P = 0.5288; Mann-Whitney). Post-treatment Gal-3 levels were 11.3 ± 3.7 (HELP; range 4.5-16.3) and 11.3 ± 3.8 (DSA; range 7.5-20.7) ng/mL. CONCLUSIONS: Circulating Gal-3 levels showed a statistically significant decrease in humans undergoing therapeutic LA. Although absolute Gal-3 reduction was ≈19-23%, this effect, combined with reducing atherogenic LDL and other inflammation mediators (e.g., CRP, fibrinogen, Lp-PLA2 ), may enhance apheresis clinical benefits. Applying new Gal-3-specific extraction technologies to apheresis may be advantageous in treating diverse pathologies that are promoted by elevated plasma Gal-3. J. Clin. Apheresis 31:388-392, 2016. © 2015 Wiley Periodicals, Inc.

HPC-A dose prediction on the optia® cell separator based on a benchmark CE2 collection efficiency: Promoting clinical efficiency, minimizing toxicity, and allowing quality control.

It has been shown that it is possible to predict the CD 34+ hematopoietic progenitor cell dose from collection procedures on TerumoBCT COBE Spectra® cell separator platform using simple variables available at the start of the procedure. In this article, we demonstrate that this can be done simply and reliably using TerumoBCT Spectra Optia® ("Optia") cell separator platform with a very close correlation between predicted and actual results (correlation coefficient 0.956). This knowledge can be used to optimize apheresis sessions and to minimize harmful effects and costs. In addition, we have shown differences in collection efficiency between healthy donors and cancer patients undergoing autologous donation. Finally, we have shown a small but significant improvement in collection efficiency for the Optia platform compared with the COBE Spectra platform.

Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation.

Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL) cholesterol and causes premature coronary heart disease. There are at least 20 million people with FH worldwide, but the majority remains undetected and current treatment is often suboptimal.To address this major gap in coronary prevention we present, from an international perspective, consensus-based guidance on the care of FH. The guidance was generated from seminars and workshops held at an international symposium. The recommendations focus on the detection, diagnosis, assessment and management of FH in adults and children, and set guidelines for clinical purposes. They also refer to best practice for cascade screening and risk notifying and testing families for FH, including use of genetic testing. Guidance on treatment is based on risk stratification, management of non-cholesterol risk factors and safe and effective use of LDL lowering therapies. Recommendations are given on lipoprotein apheresis. The use of emerging therapies for FH is also foreshadowed.This international guidance acknowledges evidence gaps, but aims to make the best use of contemporary practice and technology to achieve the best outcomes for the care of FH. It should accordingly be employed to inform clinical judgment and be adjusted for country-specific and local healthcare needs and resources.

Use of laboratory tests to guide initiation of autologous hematopoietic progenitor cell collection by apheresis: results from the multicenter hematopoietic progenitor cell collection by Apheresis Laboratory Trigger Survey.

Limited literature describes the value of laboratory "triggers" to guide collection of peripheral blood (PB) hematopoietic progenitor cells (HPCs) by apheresis [HPC(A)]. We used a web-based survey to determine which parameters are used to initiate autologous HPC(A) collection in adult and pediatric patients and to identify common practice patterns. Members of the AABB Cellular Therapy Product Collection and Clinical Practices Subsection and the American Society for Apheresis HPC Donor Subcommittee drafted and developed relevant survey questions. A web link to the survey was distributed by electronic newsletter or email. Responses from 67 programs that perform autologous HPC(A) collections, including academic medical centers (n = 46), blood centers (n = 10), community hospitals (n = 5), and a variety of other medical institutions (n = 6), were analyzed. Ninety-three percent (62/67) of programs used a laboratory parameter to initiate HPC(A) collection. In both adult (40/54, 74%) and pediatric (29/38, 76%) patients, the PB CD34+ cell count was the most common parameter used to initiate HPC(A) collection. The median PB CD34+ trigger value was 10/µL for both patient populations. Among centers routinely using the PB CD34+ cell count to initiate apheresis, 51% (22/43) first sent the test before the patient presented for collection. Although more than 90% of centers used a laboratory test to trigger apheresis in cytokine-mobilized (44/48) or chemomobilized patients (50/53), only 57% (30/53) used a laboratory trigger if the patient was mobilized with granulocyte colony-stimulating factor plus plerixafor. Forty-two percent (21/50) of programs that routinely measured the PB CD34+ count before collection and discontinued further HPC(A) collection based on product CD34+ cell yield also stopped if the PB CD34+ value before apheresis was considered too low to proceed. Most programs use the PB CD34+ cell count to trigger autologous HPC(A) collection. Some centers also use this parameter to stop further collections. Laboratory tests are used less frequently to initiate apheresis when patients are mobilized with plerixafor. These data reveal ongoing diversity in clinical practices and suggest that consensus guidelines on use of laboratory parameters may further optimize HPC(A) collection.