Apheresis Machine Research Articles

Evaluation of the Safety and Feasibility of Apheresis in Dogs: For Application in Metastatic Cancer Research.

Simple SummaryIn cases of cancer metastasis, some tumor cells circulate in blood (CTCs) and function as a seed for metastasis. These cells are important for detailed study of the molecular basis of metastasis. However, their few numbers and difficult isolation hinder its analysis. Apheresis, a process used to isolate a specific component of blood, can efficiently separate peripheral blood monocyte (PBMC), whose density is closely like that of CTCs. In the present study we used the dogs as a precious model of human’s cancers to check the safety and feasibility of apheresis and to separate PBMC and infused MCF7 cells using Spectra Optia apheresis machine (Terumo). The process was performed safely to capture PBMC and MCF7. The captured MCF7 cells were regrown up in vitro and characterized. In conclusion, Spectra Optia apheresis machine (Terumo) can be used safely to isolate CTCs from dogs blood with precautions to keep hemodynamic stability.In patients with solid tumors, circulating tumor cells (CTCs) spread in their blood and function as a seed for metastases. However, the study of CTCs has been limited by their rarity, low frequency, and heterogeneity. The efficient collection of CTCs will contribute to further research of metastatic cancers. Apheresis is a process in which the whole blood of an individual is passed through a machine that isolates a particular constituent and returns the remainder to the circulation. In the present study, we investigated the safety and feasibility of apheresis to separate peripheral blood monocytes (PBMCs), whose density is closely similar to that of CTCs, and to capture intravenously administered human breast cancer cells, MCF7s, from the dogs. No life-threatening events were observed in dogs during the apheresis process. The changes in the hemogram were transient and recovered gradually within a few days after apheresis. During apheresis, 50 mL of PBMCs could be collected from each dog. Notably, a thrombus was formed along the circuit wall during apheresis, which decreased the blood collection pressure. MCF7 cells were successfully captured by the apheresis machine. The captured cells were regrown in vitro and characterized compared with the original cells. In conclusion, apheresis could be safely performed in dogs to isolate CTCs with precautions to maintain hemodynamic stability.

Innovator Filgrastim versus Generic Filgrastim in Hematopoietic Stem Cell Transplantation Mobilization.

Methods This is a retrospective study. G-CSF was administered in the dose of 10 μg/kg subcutaneous as a single dose for 4 days. On day 5, peripheral blood stem cell (PBSC) apheresis was performed using Haemonetics MCS plus or COBE Spectra apheresis machine through a double-lumen central venous catheter. Primary outcome parameters were the total number of CD34+ HSCs/kg of recipient weight mobilized in peripheral blood and the number of days required for neutrophil and platelets engraftment, respectively. Objective We compared the effectiveness and safety of innovator filgrastim versus generic filgrastim in patients who underwent hematopoietic stem cell transplantation (HSCT). Results A total of 91 stem cell mobilizations was analyzed. There were 58 normal healthy donors for allogeneic HSCT and 33 patients for autologous HSCT. There was no statistically significant difference among groups in terms of total collected CD34+ cells value ( p = 0.609). The mean time to neutrophil engraftment was 13.7 days in the innovator group and 13.2 days in the Grafeel group ( p = 0.518). The mean time to platelet engraftment was 16.2 days in the innovator group and 14.8 days in the generic group ( p = 0.435). The patient who received generic filgrastim had more febrile episodes during the course of transplantation ( p = 0.020). Conclusion Generic filgrastim was found to be comparable to original filgrastim for peripheral blood stem cell mobilization in normal healthy donors for allogeneic HSCT and patients for autologous HSCT.

Factors driving availability of COVID-19 convalescent plasma: Insights from a demand, production, and supply model.

BackgroundCOVID‐19 Convalescent Plasma (CCP) is a promising treatment for COVID‐19. Blood collectors have rapidly scaled up collection and distribution programs.MethodsWe developed a detailed simulation model of CCP donor recruitment, collection, production, and distribution processes. We ran our model using varying epidemic trajectories from 11 U.S. states and with key input parameters drawn from wide ranges of plausible values to identify key drivers of ability to scale collections capacity and meet demand for CCP.ResultsUtilization of available CCP collections capacity followed increases in COVID‐19 hospital discharges with a lag. Utilization never exceeded 75% of available capacity in most simulations. Demand was met for most of the simulation period in most simulations, but a substantial portion of demand went unmet during early, sharp increases in hospitalizations. For epidemic trajectories that included multiple epidemic peaks, second wave demand could generally be met due to stockpiles established during the decline from an earlier peak. Apheresis machine capacity (number of machines) and probability that COVID‐19 recovered individuals are willing to donate were the most important supply‐side drivers of ability to meet demand. Recruitment capacity was important in states with early peaks.ConclusionsEpidemic trajectory was the most important determinant of ability to meet demand for CCP, although our simulations revealed several contributing operational drivers of CCP program success.

The Effect Of Product Quality, Service Quality, Price On Product Purchasing Decisions On Consumer Satisfaction

This study aims to provide empirical evidence regarding the influence of product quality, service quality, and price on the decision to purchase medical device products and their implications for consumer satisfaction. This study uses the PLS (Partial Least Square) analysis method. This study uses primary data in the form of a questionnaire and is distributed to 141 (one hundred and forty-one) respondents who are users of medical device products, namely apheresis machines. Based on the overall exposure of statistical calculations on structural model analysis and testing that partially, product quality is proven to have a positive and significant effect on purchasing decisions for medical device products, service quality is proven to have a positive and significant effect on purchasing decisions for medical device products, prices are proven to have a positive and significant effect. significant towards the decision-making of medical device product purchasing, product quality proved to have a positive and significant effect on consumer satisfaction of owned medical device products, service quality proved to have a positive and significant effect on consumer satisfaction of medical device products, price proved to have a positive and significant effect on consumer satisfaction of medical device products health. The purchase decision is proven to have a positive and significant effect on consumer satisfaction with medical device products.

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Differentiation of Monocytes into Phenotypically Distinct Macrophages After Treatment with Human Cord Blood Stem Cell (CB-SC)-Derived Exosomes.

Stem Cell Educator (SCE) therapy is a novel clinical approach for the treatment of type 1 diabetes and other autoimmune diseases. SCE therapy circulates the isolated patient's blood mononuclear cells (e.g., lymphocytes and monocytes) through an apheresis machine, co-cultures the patient's blood mononuclear cells with adherent cord blood-derived stem cells (CB-SC) in the SCE device, and then returns these "educated" immune cells to the patient's blood. Exosomes are nano-sized extracellular vesicles between 30‒150 nm existing in all biofluid and cell culture media. To further explore molecular mechanisms underlying SCE therapy and determine the actions of exosomes released from CB-SC, we investigate which cells phagocytize these exosomes during the treatment with CB-SC. By co-culturing Dio-labeled CB-SC-derived exosomes with human peripheral blood mononuclear cells (PBMC), we found that CB-SC-derived exosomes were predominantly taken up by human CD14-positive monocytes, leading to the differentiation of monocytes into type 2 macrophages (M2), with spindle-like morphology and expression of M2-associated surface molecular markers. Here, we present a protocol for the isolation and characterization of CB-SC-derived exosomes and the protocol for the co-culture of CB-SC-derived exosomes with human monocytes and the monitoring of M2 differentiation.

Manual Partial Exchange Transfusion a Cost Effective Life Saving Intervention in Sickle Cell Crisis: Single Centre Retrospective Data Analysis

Introduction: Sickle cell disease (SCD) poses a considerable health burden in lower middle income country (LMIC) like India. One ICMR survey reported about 20% of children with SCD died by the age of two years and 30% of children with SCD amongst the tribal community in India died before they reached adulthood. Data on mortality rate in the adult population with SCD is sparse. Our centre data shows that despite the availability of Hydroxyurea and supportive care, almost one-third of hospitalized Sickle Cell Crisis patients develop life threatening complications. Manual Partial Exchange Transfusion is a cost-effective intervention to decrease mortality in Sickle Cell Crisis. But perhaps, it is an underutilized therapy. In India, the cost incurred for each session of exchange transfusion, if done by the RBC apheresis machine, is $420. Whereas Manual Exchange Transfusion costs only $70(including the cost of the central venous catheter) for the first session followed by $15 for each subsequent session. Aim: A single centre retrospective data analysis to evaluate the outcome of Sickle Cell Crisis patients undergoing Manual Partial Exchange Transfusion during hospitalization. Material and Method: A total of 553 SCD patients on regular follow up at the Haemato Oncology Care Centre (HOCC) from July 2012 to July 2020 were evaluated.169 patients were hospitalized for treatment of Sickle Cell Crisis at the Bhailal Amin General Hospital and Sterling Hospital Vadodara. The data was retrieved after the IRB/Apex committee approvals for retrospective analysis. The indication for exchange transfusion was Acute Chest Syndrome 19(35%), Hepatic cell crisis 11(20%), Vaso Occlusive Crisis not responding to the conservative line of therapy in 48 hours of treatment 11(20%), Cerebrovascular Accident (CVA) 5 (9%), Avascular Necrosis of Femur with excruciating pain 3 (6%), Complicated Dengue with Multi-organ failure 3 (6 %), Priapism 1 (2%) and Splenic Sequestration 1 (2%). Central venous access was secured with a central venous catheter or dialysis catheter. Simple packed cell volume was transfused to 11(20%) patients and 5(9%) patients received platelet transfusion. The cut-off values for HB and Platelet count were 8 gm% and 50000/cumm, respectively at the time of the Manual Partial Exchange Transfusion procedure. Blood volume withdrawn was 5 to 10 ml /kg, followed by an equal volume of packed cell volume transfusion at every session. The procedure was repeated every 12 hr or 24 hr depending on the clinical condition of the patient. HbS value was reassessed post 4 sessions with repeat testing done after 2 to 4 sessions if the observed HbS value was more than 30% or more than 10% (for CVA) after 4 sessions. The endpoint was clinical recovery with HbS less than 30% or no clinical recovery despite the achievement of HbS less than 10%. In CVA the endpoint was HBS less than 10%. Results: Manual Partial Exchange Transfusion was carried out in 54/169 (32 %) hospitalized patients. The median age was 25yrs (range 5 yrs to 69 yrs), with male predominance [Males 42(77%) and females 12(23%)].Pre procedure HbF value was <10% in 13(24%), 10 to 20% in 23 (43%) and >20% in 18(33%). A total of 50 out of 54 (93%) patients recovered completely. 28 (52%) patients were hemodynamically stable with normal SPO2 on room air at the time of Manual Partial Exchange Transfusion with an average of 7 days of hospitalization. All of these patients recovered completely with less than 5 sessions of Manual Partial Exchange Transfusion. 26(49%) patients were critically ill and had an average of 12 days of hospitalization. They were on Ventilator and Inotrope support at the time of Manual Partial Exchange Transfusion. 14/26(54%) critically ill patients recovered completely with an average of 6 sessions of Manual Partial Exchange Transfusion. 12/26(46%) critically ill patients succumbed even though post exchange HBS value decreased to less than 10%. The overall mortality rate of SCD patients in this analysis was 12/553 (2.1%), significantly lower than what was historically reported as 30% in the ICMR survey. Underlying Dengue viral infection associated with Multi-organ dysfunction and Fulminant hepatic failure were risk factors for mortality observed in our study. Conclusion: Manual Partial Exchange Transfusion is highly effective in reducing mortality in Sickle Cell Crisis. It is feasible and cost-effective in small centres lacking apheresis machine facility. Disclosures No relevant conflicts of interest to declare.

Phase I and Preliminary Results of a Phase II Study (TERAPLASCoV2) of Convalescent Plasma in Patients with Severe and Life-Threatening Pneumonia Caused By Sars-Cov-2

Introduction: The current coronavirus disease- 2019 (COVID-19) pandemic has caused a sudden increase in pneumonia cases, with a case-fatality rate of 10.9% in Mexico. Two inpatient groups have been defined, with different clinical evolution: cases of severe pneumonia and those with life-threatening disease (Acute respiratory distress syndrome [ARDS], invasive mechanical ventilation [IMV] requirement, and multiorgan involvement).Currently, there is no effective treatment. Convalescent plasma (CP) has been used to treat another viral infections and outbreaks since the last century. The rationale is that neutralizing antibodies contained in CP suppress viremia and produce immunoregulation. However, an established therapeutic dose during this pandemic is lacking.Aim: To evaluate in a phase I trial the minimum effective dose of CP in severe and life-threatening disease patients and then carry out a phase II study to establish the effectiveness (overall survival at 30 days) comparing it with a non-randomized control group.Methods and design. Our study is an open-label, multicenter, non-randomized and started in May, 2020 and was approved by the ethics committee at HGE & HCN Pemex; respectively. CP donor selection: pre-donors who were infected by SARS-CoV-2 were evaluated on +30 day by serum titration (≥1:320 IgG antibody); then connected to apheresis machine to obtain 600 ml of CP that were fractionated in 200 ml bags and stored. Patients: Two groups were formed: severe and life-threating disease. CP was offered to patients who were admitted on two hospitals. Patients should meet the following criteria: SARS-CoV-2 positive for qRT- PCR, respiratory rate> 30 per minute or Kirby index <300 or IMV requirement; be older than 18 years; and sign the informed consent. Statistics: For demographic variables, the differences were evaluated with parametric or non-parametric analysis. For survival, Kaplan Meier curves were assessed for each group. A p value <0.05 was considered significant.Outcomes: A total of 110 CP bags have been transfused. The median serum IgG antibody titers were 1: 960. Dosing, phase 1. Severe group (n=14): 71% received two CP bags (400 ml) and 29% three CP bags (600 mL). Life-threatening disease group (n=10): 60% received 4 CP bags (800 ml) and 40% 3 CP bags (600 ml). Dose was established at 400 ml for the severe group and 800 ml for the life-threatening group. Security: CP infusions were well tolerated, with only 3 adverse events (2.72%) reported: one case of transfusion associated circulatory overload (TACO) that resolved with the use of loop diuretics as a serious adverse event; one fever episode (grade 1) and one case of rash (grade 1) after CP infusion.Phase II: The calculated n to be included in each arm (severe vs. life-threatening disease) is 68 and 52 patients, respectively. So far, we have included a total of 42 patients treated with CP. This entire cohort was compared with a historic group of COVID-19 patients who received other treatment strategies. Clinical characteristics on both plasma (PG) and control group (CG) are presented in table 1. We observed statistically significant differences on smoking habit, D-Dimer levels and ARDS severity between groups. The median overall follow- up was 24 days [PG 28 days vs. CG 21.5 days]. Overall Survival (OS) between PG and CG was 74% vs. 54% at 30-days respectively [HR=0.43 (C.I.95%=0.23 to 0.91, p=0.021); figure 1].We analyzed OS by group stratification: COVID-19 severity (severe disease vs. life-threatening disease) and ARDS severity. We found no difference in OS between severe disease-PG and severe disease-CG; but we observed an OS difference between life-threatening-PG and life-threatening-CG [32% vs. 5.8% at 30-days; p=0.003].ARDS-PG vs. ARDS-CG showed OS differences in moderate [59% vs. 25% at 30 days; p=0.01, respectively] and severe ARDS [63% vs. 0%; p=0.001, respectively]; however, there was not statistically significant difference between mild ARDS-PG and CG groups [89% vs. 86%; p=0.85, respectively].Conclusion: This is the first phase I trial aiming to establish an effective CP dose for COVID-19 patients, at least in México. For severe and life-threatening disease, 2 and 4 CP bags were suggested. This treatment was secure, with <3% of adverse events reported. OS could be modified using certain doses based on disease severity and pa02/Fi02 index. We will continue to include patients until the calculated n is reached.DisclosuresVillela:Roche: Other: advisory board, Speakers Bureau; amgen: Speakers Bureau.

A Simple Quick Method of Draining Red Cells from Granulocyte Concentrates Ex Vivo without the Addition of Hetastarch after Granulocytapheresis

Introduction Granulocytapheresis from healthy volunteer donors are performed regularly at our institution to treat severely neutropenic leukemia/SCT patients with overwhelming bacterial/fungal infections. 500 to 750 mL of Hespan® (6% hetastarch in 0.9% sodium chloride injection) with citrate anticoagulant is administered by aseptic addition to the input line of the centrifugation apparatus at a ratio of 1:13 to venous whole blood. The traditional method of gravity sedimentation of Granulocyte concentrates (GC) is the addition of 50 cc of 6% Hydroxyethyl starch in ACD anticoagulant which results in RBC volume reduction to &amp;lt; 5ml (range acceptable for transfusion to ABO incompatible recipients according to AABB standards). The method is time consuming, tedious and adds additional HES to the product. We streamlined the process by allowing the sedimented red cells to drain via gravity upon completion of the apheresis procedure without the addition of Hetastarch. Method: GCs are obtained from prescreened eligible (meet AABB/FDA guidelines) family/friends of the patients. G-CSF is administered as a fixed dose of 480 mcg (donors &amp;lt; 250 lbs.) or as 2 doses of 300/480 mcg (donors &amp;gt; 250 lbs) plus 8 mg of dexamethasone (without history of cataracts) 12 hours prior to the collection. 30 ml of TriCitrasol Anticoagulant (46.7% Trisodium citrate) is added to 500 ml of 6% Hetastarch in 0.9% Sodium Chloride Injection for IV use only and not more than 1000 ml is used in a single GC apheresis procedure. Our current practice is to test all O blood group donors for Anti-A Isoagglutinin titers. Cut off titers are set at &amp;lt;128. GCs from group O donors with Anti-A titers &amp;gt; 128 are drained of red cells if the recipient is non-O. For pediatric patients, our practice is to drain all GC products regardless of ABO compatibility between donor and recipient. Process: Upon completion of the Granulocytaheresis, the GC collection bag is left undisturbed hanging on the IV pole leaving all slips clamps attached. Red cells collected during the apheresis procedure settle at the base the collection bag. The collection line of the GC collection bag is clamped distal to the attachment of the sterile barrier filter inclusive of the sample bulb assembly. The clamp proximal to the sample bulb assembly needs to be left clamped. The collection bag is then sterile docked to a transfer bag (the plasma bag from the IDL set can be used) to create a closed sterile system. Two hemostats clamps are placed, one close to the inlet port of the collection bag and the other close to the sterile dock of the transfer bag. The clamps are opened slowly and the sedimented red cells are allowed to slowly drain into the transfer bag. Pressure using two fingers may be used to create a funnel to express the sedimented red cells into the port from the GC unit. When the desired amount of red cells are expressed into the transfer bag the process is stopped. The transfer bag is then removed by clamping and a relatively clean GC product is now available for transfusion. The entire process takes approximately 10-15 minutes. The GC bag is then sampled via the incorporated sample bulbs for the bag count, then labelled ready for release for transfusion. Results: We reviewed the results of six drained GCs by this method; the median Bag RBC was 0.8 x10e6/uL (range 0.06 - 0.23), Bag Hgb 0.8 g/dL (range 0.5-1.0) and Bag Hematocrit 0.7% (range 0.6-2.6). The median Bag WBC count was 10.6 x 10e10 (range 5.8 to 15.1), median bag volume 641 mL (range 462-774) and median volume processed 10526 ml (range 8800-12175 mL). We achieved our goal of reducing the red cells to &amp;lt;2 ml, providing a GC with more than the minimum yield (1.0 x 10e10) required according to AABB standards and also the availability of a GC product within 2 hours of completion for transfusion. Discussion: The use of the newer Apheresis machine allows for efficient removal of the targeted component and monitors/adjusts the depth at which the cells are collected within the Buffy coat layer based on the desired hematocrit of the collected product. Our practice is to collect a relatively clean GC product where there is less than 2 mL of red cell contamination in the GC unit. However, this is not always achieved and the GC units do have to be drained. Approximately 10-25 mL of red cells are drained depending on the collection and the GC units drained in this manner are comparable to the GCs drained after the addition of 50 cc of Hetastarch to the GC product. Disclosures No relevant conflicts of interest to declare.

Effects of intra-articular autologous mesenchymal stem cell injection under ultrasonogram guidance in patients with osteoarthritis knee

Mesenchymal stem cells therapy opened new perspective in the management of osteoarthritis. This study focuses on a randomized controlled trial pilot on 10 patients of osteoarthritis knees to evaluate the intra-articular injections of mesenchymal stem cells could improve the symptoms, functional limitation and regeneration of cartilage. Mesenchymal stem cells were obtained from peripheral blood after mobilization of blood cell with granulocyte colony stimulating factor by apheresis machine. Single dose of mesenchymal stem cells were injected into the affected joints, WOMAC questionnaires scale used to record pre and post-treatment improvement, cartilage thickness measured by high frequency ultrasonogram. Four patients were having Grade II and six were having Grade III osteoarthritis. Kellgren-Lawrence scale was used for radiological grading. Pain score were decreased at the end of 24th weeks from 14.8 ± 2.2 to 4.1 ± 1.3, Stiffness score decreased from 5.8 ± 0.6 to 0.7 ± 0.6, Physical function limitation score reduced from 46.7 ± 6.5 to 20.3 ± 2.5. There was minor improvement of range of motion and cartilage thickness changes. This study demonstrates that mesenchymal stem cells injections improves all parameters of knee osteoarthritis and minimal regeneration of damaged cartilage.

Plateletpheresis in the Era of Automation: Optimizing Donor Safety and Product Quality Using Modern Apheresis Instruments.

The increases in major surgeries, transplantations and speciality clinics have significantly increased the utilization of platelet concentrates including single donor platelets (SDP). The advantages of SDP or apheresis platelet have been discussed elaborately by previous authors as compared to random donor platelets. Here we share our experiences of plateletpheresis procedures using the modern apheresis machines with regards to product quality and donor safety. This study included 3016 procedures of plateletpheresis (1397 on Amicus and 1619 on Trima accel cell separators) on eligible donors using recommended apheresis kits. A target yield of 3 × 1011 was set as the end point of each procedure. Donor details, procedure details and donor adverse reactions if any were documented. Statistical analysis was done using the SPSS statistical package (version 13, USA). Of the total 6276 donors screened 2049 (32.6%) were deferred due to various reasons. Out of remaining 4227 eligible donors; 3016 (71.4%) underwent plateletphereis procedures based on the requirement of SDP by the patients. Mean pre-procedure platelet count and hematocrit in donors were 188.3 × 106/mL and 41.7% respectively. Mean procedure time in Amicus (76.6min) was significantly more than the Trima accel (64.3min) (p = 0.02). Platelet yield by Trima accel and Amicus was 2.96 × 1011 and 3.08 × 1011 respectively (p = 0.061). A total of 40 donors (1.33%) suffered adverse effect during or after apheresis procedures. While the modern plateletpheresis devices are both donor and user friendly at the same time they provide quality product consistently in lesser time.

Vox Sanguinis International Forum on Hospital Transfusion Services' Response to COVID‐19: Responses

Question 1Demographics:a. Beer Yaakov, Israel.b. Large academic medical center.c. 956 beds.d. 9034 RBC units issued in 2019, approximately 9000.e. 4831 confirmed SARS‐CoV‐2 cases and 17 deaths (March 31, 2020, 12:40 pm, data from the Israeli Ministry of Health).f. 9,136,000 inhabitants.g. The spread of SARS‐CoV‐2 in Israel is still increasing, but as of yesterday the rate of increase is declining sharply (from almost 30% of samples tested per day at the peak to 12% yesterday).

Apheresis-Adverse Events in Man and Machine Individualities

Adverse events due to platelet pheresis are not unheard of citrate related reactions being the most common. Most of these events are mild and self limiting. The current study describes adverse events in platelet pheresis using modern apheresis systems. This prospective study included 1455 platelet pheresis procedures done from July 2016 to December 2017. Procedures were performed on Hemonetics MCS+, Trima Accel and Cobe spectra cell separators. The endpoint of each procedure was a yield of 3 × 1011 platelets (PLTs) per unit. Donor adverse reaction if any was managed, reported, and documented. The median age of donors was 31 years with male to female ratio of 13:1. The median body surface area and body mass index were 1.64 m2 and 22.4 kg/m2, respectively. The mean PLT count of donors was 199.8 × 103/uL with a mean hemoglobin value of 13.6 g/dl. ACD infusion was significantly more in the Hemonetics MCS+, (P&lt; 0.01). Donation time was least with the Trima compared to Hemonetics MCS+ (P&lt; 0.01) and Cobe (P&lt; 0.001). Total whole blood volume processed was higher in Hemonetics MCS+, (P&lt; 0.01). Paresthesia due to citrate toxicity was the most common adverse reaction (65.3%), and vascular injury was observed in only five donors. The overall incidence of adverse reaction was 3.4%. Serious adverse events were not observed. The modern generation apheresis machines are more donors friendly and cause less adverse reactions compared to the older versions. Good donor screening, optimized donor physiognomic and hematological values and skilled operators are the key factors in reaction reduction by apheresis. Faridpur Med. Coll. J. Jan 2019;14(1): 27-30

The HPC-a Collectogram: A Useful Tool for Determining Collection Processing Volumes

Introduction Optimal mobilization is an important step in the autologous hematopoietic cell transplant procedure. Mobilization requires the administration of growth factors such as filgrastim, a granulocyte colony stimulating factor, and plerixafor, a CXCR4 antagonist, that help release hematopoietic progenitor cells (HPC) from the marrow niche. HPCs are differentiated from other cells by their expression of CD34 on the cell surface. Through monitoring of CD34+ cells, the transplant team assesses how well a donor is mobilizing and can adjust mobilization and collection plans accordingly. This enables decision-making on the use of plerixafor and the volume of whole blood to be processed (WBP). Objective We developed the HPC- A Collectogram to help determine the volume of WBP depending on the assumed collection efficiency (CE2). This tool, built in Excel utilizes embedded formulas with input variables including target CD34 dose, dosing weight, blood volume, total WBC, peripheral blood CD34%, PBCD34 count and assumed CE2 (Figure 1). The CE2 at the time of the collection is unknown however an educated guess is made based on the median CE2 for previous collections at our center. The CE2 is a measurement of the apheresis instrument's ability to separate and extract the maximum number of CD34+ cells from cells available in the peripheral blood; yet the CE2 may be heavily influenced by variables such as donor and blood characteristics, as well as apheresis machine software/program and operator adjustments. Method Utilizing the known median CE2 value as a guide, the HPC-A Collectogram can be utilized to predict collection volumes that meet exact collection goals within an acceptable range. The decision to restrict collection based on a calculated processing volume may prevent undesirable side effects of a prolonged apheresis procedure and the over-collection of HPCs. Results For example, Jane Donor, weight 69.9 Kg, height 170.2 cm, WBC 52.2 K/uL, CD34% 0.196: To use the HPC-A Collectogram to guide collection in this patient, the user should: (1) Enter values for prescribed dose and dosing weight to calculate the absolute CD34 dose. (2) Enter current height and weight into the appropriate gender column to calculate donor blood volume. (3) Enter collection day WBC and CD34% as a decimal to determine the PBCD34 and to populate WBP and the target blood volume (BV) (the number of times the donor blood volume will need to be circulated through the apheresis instrument). (4) Choose the target BV to run based on the expected efficiency. For this example, run 3.73 BVs for an expected 40% efficiency to collect 10 million CD34+ cells/kg (Figure 2). Conclusion The HPC-A Collectogram can be a useful tool to more efficiently assist transplant team members in determining the volume of WBP required to meet prescribed dosing goals for hematopoietic cell transplantation.

Comparative assessment of single-donor plateletpheresis by Haemonetics® MCS® plus and Trima Accel®.

BACKGROUND:Single-donor platelets (SDPs) prepared by sophisticated automated equipment offer several advantages over random-donor platelets and are being increasingly used to support thrombocytopenic patients. Different apheresis machines working on the principle of centrifugation are being used worldwide to collect platelets. This retrospective study was done to compare plateletpheresis on two automated cell seperators – Haemonetics® MCS® Plus and Trima Accel®.MATERIALS AND METHODS:Data for 100 single-donor plateletpheresis procedures, fifty on each machine, were retrospectively collected and analyzed. Donor characteristics were analyzed by Student's t-test and no significant difference was found between the two groups. The parameters compared between the two machines were yield, collection efficiency, blood volume processed, procedure time, acid-citrate-dextrose (ACD) used, leukodepletion achieved, quality control of the products, and adverse donor reactions.RESULTS:Platelet yield (3.054 ± 0.14 vs. 3.120 ± 0.25), quality control of the platelets, leukodepletion achieved, and donor safety were comparable in both the machines. The blood volume processed (2230.74 ± 227.01 vs. 2452.90 ± 318.61), ACD used during procedure (265.48 ± 43.21 vs. 298.10 ± 53.32), procedural time (55.92 ± 13.00 vs. 68.86 ± 12.64), and the postprocedural decrease in donor count in Trima Accel® (183.10 ± 23.99 vs. 161.44 ± 63.47) were significantly less than those in Haemonetics® MCS® Plus. The median collection efficiency of Trima Accel® was found to be greater than Haemonetics® MCS® Plus (0.000649 vs. 0.000608, P = 0.020).CONCLUSION:Both Trima Accel® and Haemonetics® MCS® Plus can collect SDPs safely and efficiently. Trima Accel® has higher collection efficiency and reduced incidence of citrate-related adverse effects. It also has better potential to optimize productivity due to decreased procedural time.

Comparison of platelet quality and the effect of platelet collection in single donor platelet collected by 2 brands of apheresis machines

Posterolateral fusion (PLF) with autogenous iliac bone graft is one of the most common surgical procedures for lumbar spinal disease. However, its limited success demands new biologically competent graft enhancers or substitutes. Although the use of direct current (DC) electrical stimulation has been shown to increase rate of successful spinal fusions, little is known about the effect of the type of current in DC stimulation.To evaluate the effects of various DC stimulators on the strength and success rate of posterolateral fusion facilitated by using a nitinol mesh container, in rats.This was an experimental animal study.A conductive, tubular nitinol mesh container was used to carry small pieces of bone grafts. The nitinol mesh container received electrical stimulation via a lead that connected the container to different types of DC stimulators. Sixty male Sprague-Dawley rats were divided into three groups (N=20 in each): a control group that underwent PLF with a nitinol container filled with autograft, a constant DC group that received a nitinol container and constant DC (100 μA), and a pulsed DC group that received a nitinol container and pulsed DC (100 μA, 100 Hz, 200 μs). The rats underwent PLF between L4 and L5, and transverse processes were grafted with bilateral iliac grafts. A stimulator was implanted subcutaneously. The rats were sacrificed 8 weeks postsurgery, and lumbar spines were removed. Spinal fusion was evaluated by microcomputed tomography, manual testing, biomechanical testing, histologic examination, and molecular analysis.All animals in the DC stimulation groups displayed solid fusion, whereas only 70% of control animals showed solid fusion. Radiographic images, biomechanical testing, histologic examination, and molecular analysis revealed improved fusion in the order control group<constant DC group<pulsed DC group. The volume of new bone mass was significantly higher in the pulsed DC group (p<.05). Fusion was more solid in the pulsed DC group than in control group (p<.05). The pulsed DC group displayed the lowest inflammatory responses.Pulsed DC electrical stimulation is efficacious in improving both strength and fusion rate in a rat spinal fusion model. In addition, tubular nitinol mesh, made of conductive suture, appears useful for holding small pieces of bone grafts and maintaining a good environment for bone fusion.Pulsed DC electrical stimulation may be potentially useful to increase the fusion rate after spinal fusion in humans. Future research is required to evaluate the safety and efficacy of tubular nitinol mesh and pulsed DC electrical stimulation in humans.

Single donor Plateletpheresis and its adverse donor reactions observed in central India

Background: Plateletpheresis is a sophisticated technology by which blood is processed by an apheresis machine that uses the principal of centrifugation to extract a desired component of the blood and returns the rest of the components to the donor in real time. Apheresis procedures are usually well tolerated, but adverse events in donor do occur in a few cases. Aim and Objective: To study the Adversed donor reactions observed during single donor Plateletpheresis. Material and Method: A retrospective, observational, study of 110 healthy voluntary donors after taking informed written consent.Results: It was observed that out of 110 Single donor Plateletpheresis only five had adverse reactions (4.54 %).Two donors had tingling sensation in perioral area. Two had nausea and vomiting i.e. vasovagal reaction of mild intensity and only one with hematoma formation.Conclusion: Apheresis performed on cell separator are safe and well tolerated having less adverse reactions however these reactions are relatively mild and easily treated.

Collection of hematopoietic stem cells and immune effector cells in small children

Apheresis procedures are standard of care for a wide range of indications in children, collection of hematopoietic stem cells being the most frequent one. With increasing numbers of hematopoietic stem cell transplants, advances in graft manipulation techniques and the development of innovative therapies using immune effector cells and gene therapy, apheresis within the pediatric population is growing in demand. While young children have higher circulating white blood cell counts and robustly mobilize hematopoietic stem cells, apheresis machines were designed for use within the adult population and apheresis procedures in children, particularly small children, can be more challenging as vascular access, collection techniques and impact of extracorporeal volumes increase the rate of adverse events. In this article we review topics of particular relevance to hematopoietic stem cell and immune effector cell collections in small children.

Evaluation of the new continuous mononuclear cell collection protocol versus an older version on two different apheresis machines.

Cell separators are routinely used to collect CD34+ blood stem cells in the context of customized stem cell transplantation procedures. The Spectra Optia (Terumo BCT) is a novel development of the precursor instrument, the Cobe Spectra (Terumo BCT). In this report, 146 autologous and 42 allogeneic donors undergoing apheresis on the Cobe Spectra using the mononuclear cell (MNC) program 4.7 or on the Spectra Optia using the new continuous mononuclear cell (cMNC) program 11.2 are compared. Viability of cells and collection efficacy within the apheresis products was comparable for autologous and allogeneic products collected with the MNC or cMNC method. However, we found a reduced duration of the apheresis procedure and lower hematocrit within the apheresis products when using the cMNC in autologous and allogeneic donors. Moreover, allogeneic donors collected substantially more CD34+ cells per kilogram of body weight when using the cMNC method. Differences in platelets before and after apheresis were substantially smaller in this cohort when compared to the cohort collected with the MNC method. Neutrophil and platelet engraftment after autologous or allogeneic transplantation with a product collected with the MNC procedure was comparable to a transplantation with a product processed according to the cMNC method. Comparison of the MNC (Cobe Spectra) and the cMNC (Spectra Optia) methods demonstrated an equal performance and outcome. However, advantages were present using the cMNC method with respect to apheresis duration and hematocrit within the apheresis product (autologous/allogeneic donors) and numbers of CD34+ cells collected, especially in allogeneic donors.

Comparative efficacy in red blood cell exchange transfusions with different apheresis machines in patients with sickle cell disease.

The purpose of this study is to compare the efficacy and side effects of two red blood cell exchange (RBCX) transfusion systems in sickle cell disease (SCD). The data is collected retrospectively from the January 2010 to March 2015. 447 RBCX transfusions were performed to 165 patients. Side effects, clinical and technical efficacy were compared in between procedures with Cobe Spectra (CS) and Spectra Optia (SO) systems. Furthermore a subgroup analyses was performed for 40 patients who had RBCX transfusions with both system at least two times. Vasoocclusive crises, preoperative period and foot ulcers (49.6, 13, and 15.2% respectively) were the common indications of RBCX transfusion. While the levels of post-RBCX HbS and the actual fraction of cells remaining (FCRa) were found significantly higher in the SO compared to CS system (p=0.018 and p=0.016 respectively), the rate of targeted hemoglobin S (HbS) levels (<30%) were same in both. The length of procedure and replacement volume were significantly lower in SO compared to CS system (p=0.025 and 0.044 respectively). Subgroup analyses of 40 patients did not reveal any statistically significant differences regarding post-procedure HbS levels, FCRa levels, replacement volume and procedure duration. The inter-rater correlation coefficient for FCRa was calculated to be 0.82. Serious adverse reactions were not observed from either system. Both systems are efficiently achieved the targeted post-procedure HbS level. The recently introduced SO apheresis system is as effective and safe as the CS system, which has been used for all indications of SCD for years.