Assessment of the soluble proteins HMGB1, CD40L and CD62P during various platelet preparation processes and the storage of platelet concentrates: The BEST collaborative study.

BACKGROUND: Structural and biochemical changes in stored platelets are influenced by collection and processing methods. This international study investigates the effects of platelet (PLT) processing and storage conditions on HMGB1, sCD40L, and sCD62P protein levels in platelet concentrate supernatants (PCs). STUDY DESIGN/METHODS: PC supernatants (n = 3748) were collected by each international centre using identical centrifugation methods (n = 9) and tested centrally using the ELISA/Luminex platform. Apheresis versus the buffy coat (BC-PC) method, plasma storage versus PAS and RT storage versus cold (4°C) were investigated. We focused on PC preparation collecting samples during early (RT: day 1-3; cold: day 1-5) and late (RT: day 4-7; cold: day 7-10) storage time points. RESULTS: HMGB1, sCD40L, and sCD62P concentrations were similar during early storage periods, regardless of storage solution (BC-PC plasma and BC-PC PAS-E) or temperature. During storage and without PAS, sCD40L and CD62P in BC-PC supernatants increased significantly (+33% and +41%, respectively) depending on storage temperature (22 vs. 4°C). However, without PAS-E, levels decreased significantly (-31% and -20%, respectively), depending on storage temperature (22 vs. 4°C). Contrastingly, the processing method appeared to have greater impact on HMGB1 release versus storage duration. These data highlight increases in these parameters during storage and differences between preparation methods and storage temperatures. CONCLUSIONS: The HMGB1 release mechanism/intracellular pathways appear to differ from sCD62P and sCD40L. The extent to which these differences affect patient outcomes, particularly post-transfusion platelet increment and adverse events, warrants further investigation in clinical trials with various therapeutic indications.

MEdical Database AnaLysIS of Japanese multiple myeloma patienTs with apheresis #2 (MEDALIST-2): the impact of plerixafor use on costs and healthcare resources during mobilization and stem cell transplantation.

Treatment for multiple myeloma (MM) can involve apheresis to mobilize hematopoietic stem cells for later autologous stem cell transplantation (ASCT), which can become costly over time. This retrospective claims database study examined healthcare resource use and medical costs associated with plerixafor, a selective CXCR4 inhibitor that mobilizes hematopoietic stem cells and minimizes apheresis times. Medical data were sampled from Japanese MM patients between April 2017 and September 2019, after the Japanese launch of plerixafor. The study population (190 plerixafor users and 180 non-users) was identified from the Medical Data Vision database, and further stratified into those using granulocyte-colony stimulating factor in monotherapy or in combination with cyclophosphamide to trigger apheresis. A descriptive comparison of patient characteristics, healthcare resource use, and medical costs across the mobilization and ASCT phases indicated plerixafor is associated with higher average total medical costs. However, plerixafor-treated patients received fewer concomitant medications and spent less time in apheresis than non-users. A comparison of non-users with a similar analysis conducted pre-plerixafor launch (2013-2017) showed general improvements to treatment independent of plerixafor. The results of this research can inform guidelines for the role of plerixafor in balancing cost-effectiveness and drug efficacy in MM treatment.

Comparison of plasmapheresis with medical apheresis in terms of efficacy and cost in the acute treatment of hypertriglyceridemia in children with lipoprotein lipase deficiency.

OBJECTIVES: We aimed to compare plasmapheresis and medical apheresis as lipid-lowering therapies in children with familial lipoprotein lipase (LPL) deficiency. METHODS: The data of 13 patients who were followed up after a diagnosis of LPL deficiency were retrospectively analyzed. Plasma triglyceride, cholesterol, amylase, and lipase values and complications were recorded before and after each patient underwent plasmapheresis or medical apheresis. RESULTS: The mean follow-up period of the patients was 99.64 ± 52.92 months in the medical apheresis group and 118 ± 16.97 months in the plasmapheresis group. While the mean triglyceride level before plasmapheresis was 1,875.38 ± 547.46 mg/dL, it was 617 ± 228.28 mg/dL after plasmapheresis. While the mean triglyceride level before medical apheresis was 1,756.86 ± 749.27 mg/dL, it was found to be 623.03 ± 51.36 mg/dL after medical apheresis. Triglyceride levels were decreased by 59.62% with medical apheresis and 65.57% with plasmapheresis. The cost of treatment for medical apheresis was found to be lower compared to plasmapheresis 296.93 ± 29.94 Turkish lira (USD 43.34 ± 4.01) vs. 3,845.42 ± 156.17 Turkish lira (USD 561.37 ± 20.93; p<0.001). CONCLUSIONS: Although there is no standardized strategy for the acute treatment of hypertriglyceridemia due to LPL deficiency, medical apheresis is a safe and effective treatment with a low risk of side effects. Unlike plasmapheresis, medical apheresis can be performed in any center, which is another important advantage of the procedure.

Adopting a vein assessment tool improves procedural outcomes in double dose platelet collections - A prospective study.

BACKGROUND: This study aims to determine the phlebotomy and procedural outcomes using a vein assessment tool (VAT) in Double Dose Platelet (DDP) collections by apheresis. METHODS: VAT was based on assessing vein visibility, palpation and size with maximum score of 12 and the least being 0 and the scores were graded as adequate and inadequate. A vein-viewer was used for studying cubital vein patterns (type 1-5). Phlebotomy outcome was defined based on need for re-puncture. Procedural outcomes in terms of target yield attained and RBC reinfusion completed. Chi square test and Mann- Whitney U test were used to assess the vein score and pattern against phlebotomy and procedural outcome. RESULTS: Out of 200 DDP collections, the phlebotomy was successful in 88 % with good procedural outcome in 94 % donations. The cut off in VAT scores for successful phlebotomy was ≥8 (AUC: 70 %). Median vein scores of the arm selected for phlebotomy was 9 and graded adequate in 154 (77 %) donations.Odds for successful phlebotomy was 3.7 times higher when donors had an adequate VAT grades(p = 0.003). Procedural outcomes was favourable when at least one arm had adequate VAT grade when compared to both arms being inadequate (98 % vs 82 %; p < 0.001). Phlebotomy failure was more with first time apheresis donors than repeat apheresis donors (p = 0.014). CONCLUSION: This study indicated that a VAT score with a cut off of ≥8 had better phlebotomy and procedural outcomes in DDP collections and that donor with at least one arm having the VAT score of ≥8 are preferred for DDP collections.

Taking therapeutic apheresis services to patients in South Africa: An eight year review of SANBS mobile therapeutic apheresis service, 2013-2020.

INTRODUCTION: A 20 year review of health and health care presents the multiple challenges faced by South Africans. Health and poverty is highlighted with 45% of population living on approximately US$ 2 per day and 10 million living on less than US$ 1 per day. Widening disparities in health care provision between public and private sector hospital services exist. The South African population includes the largest number of people living with HIV infection/AIDS of any country in the world, with a 70% estimate of 7.5 million people living with HIV on antiretroviral therapy. The South African National Blood Service provides a mixed model therapeutic apheresis service including mobile service and fixed-site therapeutic apheresis and an apheresis collection of hematopoietic stem cell (HPC-A) service. Therapeutic apheresis modalities offered by SANBS include plasmapheresis, red cell exchange, leukocyte and platelet reduction. In addition, collection of plasma, thrombocytes, mononuclear cells including CD34+ cells (HPCs) and granulocytes by apheresis for plasma and cellular therapies, and customised apheresis products for research purposes is offered. An operational database for the period 2013 to 2020 was reviewed to characterise the SANBS's mixed therapeutic apheresis service and HPC-A service from 2013 to 2020 in terms of patient numbers, patient demographics, patient procedures, therapeutic apheresis indication or diagnosis, therapeutic apheresis modality, hospital service type, and the American Society for Apheresis (ASFA) category of diagnosis. METHODS: A retrospective review of therapeutic apheresis patients referred to SANBS characterising patient numbers, patient demographics, patient procedures, therapeutic apheresis indication or diagnosis, therapeutic apheresis modality (Linz, 2017), hospital service type, and the ASFA category of diagnosis (Padmanabhan et al., 2019) for the period 01 January 2013 to 31 December 2020 was completed. Data is obtained from a SANBS operational routinely utilised to record patient procedure data. Patient procedure data is manually recorded by apheresis nurses and indexed on to the operational database, with both processes audited. The review period is a convenience sample. Storage of the database and access of the operational database is in compliance with the Protection of Personal Information Act (Government Gazette, 2013). Therapeutic apheresis modalities analysed include Plasmapheresis, Red Cell Exchange, Leukopheresis, Thrombocytapheresis, Lymphocyte collection, Granulocyte collection, Haematopoietic stem cell collection by apheresis and customised apheresis products for research purposes. Customised apheresis products for research purposes is excluded from this review. Descriptive statistics is used. RESULTS: For the review period, 2,485 unique patients with 120 unique indications as recorded by referring clinicians received 13,518 procedures involving 7 therapeutic apheresis modalities at 78 hospitals (21 public sector and 57 private sector) and at 3 SANBS blood donor centres in 7 provinces of South Africa. The age range of patients serviced is 4 months to 90 years (median = 39.5 years) (figure 1), 91% by procedure count was for patients 21 years of age or older, 62% were female, with 10,783 (79.6%) procedures performed in public sector hospitals. In all patients, the most common indications was plasmapheresis for thrombotic thromobocytopaenic purpura (52.5% of cumulative procedures), HPC-A for multiple myeloma (7.86%) and Antibody-mediated kidney transplant rejection (4.90%). Plasmapheresis was the most common therapeutic apheresis modality used (82.5% of cumulative procedures) followed by HPC-A (13.7%) and leukoreduction (3.39%). A range of indications for plasmapheresis (n = 65) and HPC-A (n = 41) were observed. Red cell exchange procedures was performed for patients with severe malaria and sickle cell disease indications. For leukoreduction indications, all patients were adults managed in public sector facilities and all were symptomatic. The most common indications were Chronic Myelogenous Leukemia, Chronic Lymphocytic Leukaemia and Multiple Myeloma. A pooled, total white cell count average of 457 × 109/L (range 141-689 × 109/L) prior to first procedure. Despite complex challenges for a national mixed model service, successful patient outcomes in emergent indications such as TTP (Louw et al., 2018; Swart et al., 2019) and engraftment post HPC-A in HSCT in multiple centres (Glatt, personal communication) are reported. CONCLUSION: The review confirms that apheresis medicine is increasingly used in South Africa in patients in both public and private sector, with the most common modalities being plasmapheresis, HPC-A and leukoreduction. Patients with HIV-associated TTP is the most commonly referred patient in both paediatric and adult patients and this is anticipated to continue. A growing HSCT transplant network capacity in South Africa is augmented through the mixed model mobile and fixed-site therapeutic apheresis services, including a mobile HPC-A service. The increasing number of HPC-A is a trend towards increasing numbers of patients support to HSCT for both adults and paediatric patients in private and public sector hospitals.

Homozygous Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is an inherited disorder with retarded clearance of plasma LDL caused by mutations of the genes involved in the LDL receptor-mediated pathway and most of them exhibit autosomal dominant inheritance. Homozygotes of FH (HoFH) may have plasma LDL-C levels, which are at least twice as high as those of heterozygous FH (HeFH) and therefore four times higher than normal levels. Prevalence of HoFH had been estimated as 1 in 1,000,000 before but more recent genetic analysis surveys predict 1 in 170,000 to 300,000. Since LDL receptor activity is severely impaired, HoFH patients do not or very poorly respond to medications to enhance activity, such as statins, and have a poorer prognosis compared to HeFH. HoFH should therefore be clinically distinguished from HeFH. Thorough family studies and genetic analysis are recommended for their accurate diagnosis.Fatal cardiovascular complications could develop even in the first decade of life for HoFH, so aggressive lipid-lowering therapy should be initiated as early as possible. Direct removal of plasma LDL by lipoprotein apheresis has been the principal measure for these patients. However, this treatment alone may not achieve stable LDL-C target levels and combination with drugs should be considered. The lipid-lowering effects of statins and PCSK9 inhibitors substantially vary depending on the remaining LDL receptor activity of individual patients. On the other hand, the action an MTP inhibitor is independent of LDL receptor activity, and it is effective in most HoFH cases.This review summarizes the key clinical issues of HoFH as well as insurance coverage available under the Japanese public healthcare system.

Current state of therapeutic apheresis and cellular therapy education for transfusion medicine fellows in the United States.

BACKGROUND: Numerous conditions are responsive to therapeutic apheresis (TA) and cellular therapy (CT) treatments. Both TA and CT are two broad and diverse knowledge fields within transfusion medicine (TM). We therefore sought to survey all the TM fellowship program directors (PDs) in the United States to examine the current fellow state education in TA and CT. METHODS: A 37-question survey was sent to all PDs to collect details of TA and CT training for TM fellows. RESULTS: Responses from 29/51 (56.9%) surveyed programs were received. Most PDs considered TA and CT training for their fellows more than adequate. Two PDs from programs that did not directly oversee TA and CT services at their training sites stated that their program's training in these two areas were only "slightly adequate" or "moderately inadequate." Detailed analysis of training in TA, cell collection, and CT suggests that trainees from programs with direct oversight of these services had longer training and more learning experiences compared to those in which outside rotations were required. CONCLUSIONS: Transfusion medicine fellowship training in TA and CT varies. Most respondents, and particularly those from programs directly overseeing TA services, reported their fellows were adequately prepared in TA. Cellular therapy collections and laboratory operations, however, are less consistent areas of training despite the rapid expansion of these fields. Our survey suggests that a greater emphasis in CT training is needed.

Lipoprotein apheresis and PCSK9 inhibitors for severe familial hypercholesterolaemia: Experience from Australia and New Zealand.

INTRODUCTION: Severe familial hypercholesterolaemia (FH) causes premature disability and death due to atherosclerotic cardiovascular disease and is refractory to standard lipid-lowering therapies. Lipoprotein apheresis (LA) has long been a standard of care for patients with severe FH, but is invasive, expensive and time-consuming for patients and their caregivers. Newer drug therapies, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, may reduce the need for LA. MATERIALS AND METHODS: We audited the records of 16 patients (eight homozygous, eight heterozygous) treated with LA in Australia and New Zealand, 14 of whom subsequently commenced PCSK9 inhibitor therapy. LA was performed by cascade filtration in all centres. RESULTS: LDL-cholesterol was acutely lowered by 69 ± 7% in patients with homozygous FH and by 72 ± 9% in those with heterozygous FH, representing time-averaged reductions of 36 ± 12% and 34 ± 5%, respectively. LA was well-tolerated, and patients reported comparable quality of life to population and disease-related norms. After commencement of PCSK9 inhibitors, four of seven patients with homozygous FH had meaningful biochemical responses, with a reduction in the frequency of LA permitted in one patient and complete cessation in another. Four of seven patients with heterozygous FH were able to be managed without LA after commencing PCSK9 inhibitors. CONCLUSION: While PCSK9 inhibitors have reduced the need for LA, some patients with severe FH continue to require LA, and will require it for the foreseeable future. However, emerging therapies, including angiopoetin-like 3 inhibitors, may further reduce the need for LA.

Apheresis education in Canadian residency programs: A needs assessment.

Indications for therapeutic and donor apheresis continue to increase and expand into new domains of therapy. The level and amount of apheresis education in residency programs remains heterogeneous, which may translate into varying degrees of clinical confidence in providing care. The purpose of this study was to assess Canadian clinicians' perceptions of their apheresis training in order to help demonstrate a need for a concrete apheresis education in residency curricula. A 22-question survey was distributed to Canadian graduates who recently completed training (2013-2017) in the following specialties: hematology, nephrology, transfusion medicine, and hematologic pathology. Questions regarding clinician perception of their training were asked using a Likert scale. Fifty-seven survey responses (32% response rate) were obtained from recent graduates from hematology (29/57, 51%), nephrology (21/57, 37%), hematologic pathology (4/57, 7%) and transfusion medicine (3/57, 5%). Although most respondents (68%) received some form of apheresis exposure during residency, only 23% reported a formal apheresis rotation. Only 40% felt that the amount of time devoted to apheresis education was sufficient, and only four respondents (7%) felt confident providing independent apheresis care at the end of training. Overall, these findings suggest that a common, dedicated apheresis curriculum in these training programs could possibly increase knowledge and competence of trainees, and provide a more solid foundation in apheresis for future practice.

Heparin-induced lipoprotein precipitation apheresis in dyslipidemic patients: A multiparametric assessment.

Low-density lipoprotein (LDL) apheresis (LA) selectively eliminates lipoproteins containing apolipoprotein B 100 (ApoB100) on patients affected by severe dyslipidemia. In addition to lowering lipids, LA is thought to exert pleiotropic effects altering a number of other compounds associated with atherosclerosis, such as pro- and anti-inflammatory cytokines or pro-thrombotic factors. More knowledge needs to be gathered on the effects of LA, and particularly on its ability to modify blood components other than lipids. We performed a multiparametric assessment of the inflammatory, metabolic and proteomic profile changes after Heparin-induced lipoprotein precipitation (H.E.L.P.) apheresis on serum samples from nine dyslipidemic patients evaluating cholesterol and lipoproteins, plasma viscosity and density, metabolites, cytokines, PCSK9 levels and other proteins selectively removed after the treatment. Our results show that H.E.L.P. apheresis is effective in lowering lipoprotein and PCSK9 levels. Although not significantly, complement and inflammation-related proteins are also affected, indicating a possible transient epiphenomenon induced by the extracorporeal procedure.

Assessment of haematopoietic progenitor cell counting with the Sysmex® XN-1000 to guide timing of apheresis of peripheral blood stem cells.

BACKGROUND: Successful peripheral blood stem cell (PBSC) collection depends on optimal timing of apheresis, as usually determined by flow cytometry CD34-positive (+) cell count in peripheral blood (PB). Since this method is costly and labour-intensive, we evaluated the use of the Hematopoietic Progenitor Cell count programme on a Sysmex® XN haematologic analyser (XN-HPC) as a rapid and inexpensive alternative for predicting CD34+ cell count in PB samples. MATERIALS AND METHODS: Haematopoietic progenitor cell and CD34+ cell counts were compared using 273 PB samples collected from 78 healthy donors and 72 patients who underwent PBSC transplantation. We assessed the effectiveness of the XN-HPC in safely predicting pre-harvest CD34+ counts. The most efficient cut-off values of XNHPC were identified. We also evaluated the imprecision (coefficient of variation, CV) and functional sensitivity. RESULTS: Imprecision of the XN-HPC count was <6.3% on daily measurement of three levels of quality control material. Functional sensitivity was 8.9×106/L. A cut-off value of ≥62×106/L XN-HPC for multiple myeloma (MM) patients and ≥30×106/L for all other subjects had both 100% specificity and 100% positive predictive value for identifying samples with CD34+ cells ≥20×106/L. An XN-HPC threshold of <13×106/L identified preharvest CD34+ cell count <10×106/L with 100% sensitivity and 100% negative predictive value. DISCUSSION: The XN-HPC is a fast, easy and inexpensive test that can safely improve apheresis workflow thus possibly replacing other more expensive CD34 counts currently performed and promoting optimal timing of PBSC collection.

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.

[How to implement a complete apheresis program within a hemodialysis unit]. / Comment mettre en place un plateau technique d'aphérèses.

Many apheresis techniques can be performed in a blood-bank facility or a hemodialysis (HD) facility. However, it makes sense to perform apheresis in a hemodialysis facility as apheresis involves extra-corporeal circuits and because HD can be performed at the same time as apheresis (tandem procedure). Apheresis techniques comprise therapeutic plasma exchange, double-filtration plasmapheresis, and its derivative (rheopheresis and LDL-apheresis), and immunoadsorption (specific and semi-specific). We have setup an apheresis platform in our hospital that fulfills health recommendations. This process has involved financial investment and significant human resources, and has enabled us to network with different specialties (neurology, hematology, vascular medicine). We have setup protocols according to the type of pathology to be treated by apheresis, and to monitor clinical and biological data for each apheresis session. The main side effects of apheresis are a fall in blood pressure when a session is initiated, an increase in fluid overload, hypocalcemia, and the loss of some essential plasmatic factors. However, these side-effects are easily identified and can be properly managed in real time. Within two-years, we have performed 1845 apheresis sessions (134 patients). Of these, 66 received apheresis before and/or after kidney transplantation for ABO and/or HLA incompatibility (desensitization), for humoral rejection, or in the setting of relapsing focal-segmental glomerulosclerosis. Our patients' outcomes have been similar to those reported in the literature. The other 68 patients had various conditions. Because our program is now well-established, we are currently forming a specialist center to train physicians and nurses in the various apheresis techniques/procedures.

Current Role of Lipoprotein Apheresis.

PURPOSE OF REVIEW: Lipoprotein apheresis is a very efficient but time-consuming and expensive method of lowering levels of low-density lipoprotein cholesterol, lipoprotein(a)) and other apoB containing lipoproteins, including triglyceride-rich lipoproteins. First introduced almost 45 years ago, it has long been a therapy of "last resort" for dyslipidaemias that cannot otherwise be managed. In recent years new, very potent lipid-lowering drugs have been developed and the purpose of this review is to define the role of lipoprotein apheresis in the current setting. RECENT FINDINGS: Lipoprotein apheresis still plays an important role in managing patients with homozygous FH and some patients with other forms of hypercholesterolaemia and cardiovascular disease. In particular, patients not achieving treatment goals despite modern lipid-lowering drugs, either because these are not tolerated or the response is insufficient. Recently, lipoprotein(a) has emerged as an important cardiovascular risk factor and lipoprotein apheresis has been used to decrease lipoprotein(a) concentrations in patients with marked elevations and cardiovascular disease. However, there is considerable heterogeneity concerning the recommendations by scientific bodies as to which patient groups should be treated with lipoprotein apheresis. Lipoprotein apheresis remains an important tool for the management of patients with severe drug-resistant dyslipidaemias, especially those with homozygous FH.

Comparison and cost analysis of three protocols for mobilization and apheresis of haematopoietic progenitor cells.

INTRODUCTION: Autologous bone marrow transplantation is a component of the malignant hemopathy therapy. The preferred mobilization and collection method is apheresis. The aim of this study is to compare three protocols analyzing the effect of plerixafor, higher dose of G-CSF and large volume leukapheresis (LVL). MATERIALS AND METHODS: A retrospective cohort study including 119 patients referred for mobilization. Three protocols were compared: (a) G-CSF 10 µg/kg/day subcutaneous (sc) × 4 days mobilizing 1 to 1.5 blood volumes. (b) G-CSF 10 µg/kg/day sc × 4 days + plerixafor 0.24 mg/kg/day sc preventively or as a rescue agent mobilizing 1 to 1.5 blood volumes. (c) G-CSF 20 µg/kg/day sc × 4 days ± plerixafor 0.24 mg/kg/day sc preventively or as a rescue agent mobilizing 3 to 4 blood volumes. RESULTS: The average number of days of apheresis was reduced to 1.37 with protocol 3. The average cost per patient was reduced by 67% compared with protocol 2 and increased by only 5% compared with protocol 1, reducing the failure rate to 0%. CONCLUSION: Adding preemptive or rescue plerixafor (protocol 2) to G-CSF 10 µg/kg/day alone (protocol 1) did not improve the days of apheresis nor the number of CD34+ cells collected but had higher cost and failure rate. Using LVL, plerixafor and G-CSF 20 µg/kg/day (protocol 3) decreased the number of sessions to 1.37, reduced the failure rate to 0% and led to a significant increase in the number of CD34+ cells collected without toxicity and with a similar cost to protocol 1.

Concentrado de plaquetas de donante único en pacientes plaquetopénicos / Single Donor Platelet Concentrate in Platelettopenic Patients

CONTEXTO CLÍNICO: Se define plaquetopenia como un recuento de plaquetas menor a 150.000/mm3. Dentro de las causas se destacan la infección aguda, las enfermedades oncohematológicas, enfermedades hepáticas, la inducida por drogas (diez casos por millón personas-año, en Estados Unidos y Europa), la púrpura trombocitopénica inmune (100 casos por millón de personas-año, en Estados Unidos), la púrpura trombótica trombocitopénica (cuatro a 11 casos por millón de personas-año en Estados Unidos), el síndrome urémico hemolítico y la coagulación intravascular diseminada, entre otras. Los pacientes con un recuento plaquetario mayor a 50.000/mm3 raramente presentan síntomas. Un recuento entre 30.000 y 50.000/mm3 puede llegar a manifestarse con púrpura. Valores de plaquetas entre 10.000 a 30.000/mm3 puede causar sangrado ante un traumatismo mínimo, mientras que un recuento inferior a 5.000/mm3 puede producir sangrado espontáneo y constituir una emergencia hematológica. TECNOLOGÍA: A partir de una donación de sangre total, mediante centrifugaciones sucesivas se obtienen diferentes componentes sanguíneos, que pueden infundirse a varios enfermos (típicamente concentrados de hematíes, concentrado de plaquetas y plasma fresco). Los procedimientos más utilizados para preparar los CP estándar de sangre total pueden dividirse en aquellos que emplean el método del plasma rico en plaquetas obtenido tras centrifugación inicial débil de las unidades de sangre, o métodos de buffy coat (capa leucocítica), por centrifugación inicial intensa. En ambos casos, inmediatamente después del fraccionamiento se pueden emplear filtros para obtener un producto leucorreducido. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de aféresis de plaquetas de donante único para pacientes con plaquetopenia y requerimiento de transfusiones. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron una RS, dos estudios observacionales, cinco GPC, y cuatro informes de políticas de cobertura de aféresis de plaquetas de donante único. CONCLUSIONES: Evidencia de muy baja calidad no permite establecer si los concentrados de plaquetas de donante único reducen las infecciones virales y bacterianas, y reacciones alérgicas menores relacionadas con la transfusión, en comparación con los concentrados plaquetarios provenientes de sangre entera de donantes múltiples. En cuanto a la injuria pulmonar relacionada con la transfusión, ambos preparados, tendrían un riesgo similar. La mayoría de las guías de práctica clínica consideran a las dos alternativas como válidas. La mayoría de las políticas de cobertura relevadas no hacen mención específica respecto a la aféresis de plaquetas de donante único. Si bien no se encontraron estudios de costo efectividad, impacto presupuestario ni organizacional, el costo no es alto en relación con su comparador y el impacto presupuestario esperado es pequeño lo que hace creer que podría tener una costo-efectividad razonable.

The use of a medico economic database as a part of French apheresis registry.

An apheresis registry is a part of each learned apheresis society. The interest in this is obvious, in terms of knowledge of the practice of apheresis, adverse events, and technical issues. However, because of the weight of data entry it could never be exhaustive and some data will be missing. While continuing our registry efforts and our efforts to match with other existing registries, we decided to extend the data collection to a medico-economic database that is available in France, the Programme de Médicalisation du Système d'Information (PMSI) that has covered reimbursement information for each public or private hospital since 2007. It contains almost all apheresis procedures in all apheresis fields, demographic patient data, and primary and related diagnoses, among other data. Although this data does not include technical apheresis issues or other complications of the procedures, its interest is great and it is complementary to the registry. From 2003-2014, we have recorded 250,585 apheresis procedures, for 48,428 patients. We showed that the data are reliable and exhaustive. The information shows a perfect real life practice in apheresis, regarding indications, the rhythm and the duration of apheresis treatment. This prospective data collection is sustainable and allows us to assess the impact of healthcare guidelines. Our objective is to extend the data collection and match it to other existing databases; this will allow us to conduct, for example, a cohort study specifically for ECP.

Spectra Optia® for Automated Red Blood Cell Exchange in Patients with Sickle Cell Disease: A NICE Medical Technology Guidance.

The Spectra Optia® automated apheresis system, indicated for red blood cell exchange in people with sickle cell disease, underwent evaluation by the National Institute for Health and Care Excellence, which uses its Medical Technologies Advisory Committee to make recommendations. The company (Terumo Medical Corporation) produced a submission making a case for adoption of its technology, which was critiqued by the Newcastle and York external assessment centre. Thirty retrospective observational studies were identified in their clinical submission. The external assessment centre considered these were of low methodological and reporting quality. Most were single-armed studies, with only six studies providing comparative data. The available data showed that, compared with manual red blood cell exchange, Spectra Optia reduces the frequency of exchange procedures as well as their duration, but increases the requirement for donor blood. However, other clinical and patient benefits were equivocal because of an absence of robust clinical evidence. The company provided a de novo model to support the economic proposition of the technology, and reported that in most scenarios Spectra Optia was cost saving, primarily through reduced requirement of chelation therapy to manage iron overload. The external assessment centre considered that although the cost-saving potential of Spectra Optia was plausible, the model and its clinical inputs were not sufficiently robust to demonstrate this. However, taking the evidence together with expert and patient advice, the Medical Technologies Advisory Committee considered Spectra Optia was likely to save costs, provide important patient benefits, and reduce inequality, and gave the technology a positive recommendation in Medical Technology Guidance 28.

Rupture of the stem cell bag before stem cell infusion: Evolving standard operating procedures.

The lives of recipients of peripheral blood progenitor cells (PBPC) depend upon the availability of PBPC. Rupture of stem cell bags does occur and can have devastating consequences. Each transplant center should agree on a rescue procedure and train its personnel to use it. We provide an example of such a procedure, and its update after the procedure was used for the first time.

[Innovative technology and blood safety]. / Innovations technologiques et sécurité transfusionnelle.

If technological innovations are not enough alone to improve blood safety, their contributions for several decades in blood transfusion are major. The improvement of blood donation (new apheresis devices, RFID) or blood components (additive solutions, pathogen reduction technology, automated processing of platelets concentrates) or manufacturing process of these products (by automated processing of whole blood), all these steps where technological innovations were implemented, lead us to better traceability, more efficient processes, quality improvement of blood products and therefore increased blood safety for blood donors and patients. If we are on the threshold of a great change with the progress of pathogen reduction technology (for whole blood and red blood cells), we hope to see production of ex vivo red blood cells or platelets who are real and who open new conceptual paths on blood safety.