Apheresis Centers Research Articles

The German Lipoprotein Apheresis Registry (GLAR) \u2013 almost 5\xa0years on

BackgroundSince 2005 an interdisciplinary German apheresis working group has been established by members of both German Societies of Nephrology and of Lipidologists and completed the data set for the registry according to the current guidelines and the German indication guideline for apheresis in 2009. In 2011 the German Lipoprotein Apheresis Registry (GLAR) was launched and data are available over nearly 5 years now.Methods and resultsDuring the time period 2012–2016, 71 German apheresis centers collected retrospective and prospective observational data of 1435 patients undergoing lipoprotein apheresis (LA) treatment of high LDL-C levels and/or high Lp (a) levels suffering from cardiovascular disease (CVD) or progressive CVD. A total of 15,527 completely documented LA treatments were entered into the database. All patients treated by LA showed a median LDL-C reduction rate of 67.5%, and a median Lp (a) reduction rate of 71.1%. Analog to the Pro(a)LiFe pattern, patient data were analyzed to the incidence rate of coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y‑1) and prospectively two years on LA treatment (y + 1 and y + 2). During two years of LA treatment a MACE reduction of 78% was observed. In the years considered, side effects of LA treatment were low (5.9%) and mainly comprised puncture problems.ConclusionsThe data generated by the GLAR shows that LA lowers the incidence rate of cardiovascular events in patients with high LDL-C and/or high Lp (a) levels, progressive CVD, and maximally tolerated lipid lowering medication. In addition, LA treatments were found to be safe with a low rate of side effects.

The rationale and design of the national familial hypercholesterolemia registries in Turkey: A-HIT1 and A-HIT2 studies.

Familial hypercholesterolemia (FH) is a genetic disease characterized by extremely high levels of cholesterol, leading to premature atherosclerosis. Although many countries have already addressed the burden of FH by means of national registries, Turkey has no national FH registry or national screening program to detect FH. Creation of a series of FH registries is planned as part of Turkish FH Initiative endorsed by the Turkish Society of Cardiology to meet this need. This article provides detailed information on the rationale and design of the first 2 FH registries (A-HIT1 and A-HIT2). A-HIT1 is a nationwide survey of adult homozygous FH (HoFH) patients undergoing low-density lipoprotein (LDL) apheresis (LA) in Turkey. A-HIT1 will provide insight into the clinical status of HoFH patients undergoing LA. Primary objective of this cross-sectional study is to identify how HoFH patients on LA are managed. Inclusion criteria are age >12 years, diagnosis of HoFH, and regular LA treatment. All available apheresis centers were electronically invited to participate in the study. The principal physicians of each center will respond to a questionnaire regarding their attitude toward LA. For each patient, another questionnaire will be used to collect data on clinical status, medication use, and disease data. In addition, patients will be asked to complete self-report questionnaires that provide information on quality of life, disease-related anxiety, and depression. A-HIT2 is a registry of adult FH patients presenting at outpatient clinics. At least 1000 FH patients will be recruited from 30 outpatient clinics representing the 12 statistical regions in Turkey based on the EU NUTS classification. Sites specializing in cardiology, internal medicine, and endocrinology were invited to participate. The primary objective of this cross-sectional study is to determine clinical status and management of patients in Turkey diagnosed with FH. Eligibility for screening was defined as having LDL-cholesterol level >160 mg/dL. Inclusion criteria are age >18 years and diagnosis as possible FH (total score of >2 according to Dutch Lipid Clinic Network criteria). In addition to measuring clinical status of patients, a short survey to assess patient level of disease awareness will also be administered. A-HIT1 and A-HIT2 are the first nationwide FH registries in Turkey and will provide important information on the management of Turkish FH patients. In addition, it is planned that they will guide establishment of a national policy for the diagnosis and treatment of FH in Turkey.

Improved planning of leukapheresis endpoint with customized prediction algorithm: minimizing collection days, volume of blood processed, procedure time, and citrate toxicity.

Increased emphasis on cost and productivity in apheresis centers calls for a proficient and predictable hematopoietic progenitor cell (HPC) collection. Therefore, the aim of this study was to determine the value of a customized predictive algorithm that estimates how many blood volumes are required to process for a targeted CD34 cell dose. Retrospective analysis was performed on 107 HPC collections completed on the Spectra Optia MNC from January 2013 to June 2014 in 51 patients and 12 donors. In December 2014, a prediction algorithm was implemented, designed from data acquired since January 2013, by linear regression of preapheresis CD34 cell counts (pre-CD34) versus collected CD34 cell dose per volume blood processed. CD34 collection efficiencies (CE2) of 51.9±1.7% (mean±SEM) and 57.5±3.0% were observed in autologous and allogeneic procedures, respectively. After implementation of the algorithm, the mean number of collections per patient declined from 1.97 to 1.5. Accordingly, the frequency of patients requiring single-day collections increased from 35% to 57%. All donors were collected in single procedures, although only 12.2±1.1L blood was processed, including for National Marrow Donor Program collections. Cumulative procedure time, processed blood volume, product volume, infused anticoagulant volume, and symptomatic calcium administration decreased in patients, and overcollection was limited. A prediction algorithm can provide great value in the planning of leukapheresis, which may optimize resource utilization and capacity of the unit. In addition, predictability was facilitated by a proficient and consistent performance of the Spectra Optia MNC.

Extracorporeal photopheresis practice patterns: An international survey by the ASFA ECP subcommittee.

Although many apheresis centers offer extracorporeal photopheresis (ECP), little is known about current treatment practices. An electronic survey was distributed to assess ECP practice internationally. Of 251 responses, 137 met criteria for analysis. Most respondents were from North America (80%). Nurses perform ECP at most centers (84%) and the majority of centers treat adults only (52%). Most centers treat fewer than 50 patients/year (83%) and perform fewer than 300 procedures/year (70%). Closed system devices (XTS and/or Cellex) are used to perform ECP at most centers (96%). The most common indications for ECP are acute/chronic skin graft versus host disease (89%) and cutaneous T-cell lymphoma (63%). The typical wait time for ECP treatment is less than 2 weeks (91%). Most centers do not routinely perform quality control assessment of the collected product (66%). There are device-specific differences in treatment parameters. For example, XTS users more frequently have a minimum weight limit (P = 0.003) and use laboratory parameters to determine eligibility for treatment (P = 0.03). Regardless of device used, the majority of centers assess the clinical status of the patient before each procedure. Greater than 50% of respondents would defer treatment for hemodynamic instability due to active sepsis or heart failure, positive blood culture in the past 24 h or current fever. This survey based study describes current ECP practices. Further research to provide evidence for optimal standardization of patient qualifications, procedure parameters and product quality assessment is recommended.

Systematic Review of Low-Density Lipoprotein Cholesterol Apheresis for the Treatment of Familial Hypercholesterolemia.

BackgroundApheresis is an important treatment for reducing low‐density lipoprotein cholesterol (LDL‐C) in patients with familial hypercholesterolemia (FH). We systematically reviewed the current literature surrounding LDL‐C apheresis for FH.Methods and ResultsElectronic databases were searched for publications of LDL‐C apheresis in patients with FH. Inclusion criteria include articles in English published in 2000–2013 that provide descriptions of practice patterns, efficacy/effectiveness, and costs related to LDL‐C apheresis in patients with FH. Data were stratified by country and FH genotype where possible. Thirty‐eight studies met the inclusion criteria: 8 open‐label clinical trials, 11 observational studies, 17 reviews/guidelines, and 2 health technology assessments. The prevalence of FH was not well characterized by country, and underdiagnosis was a barrier to FH treatment. Treatment guidelines varied by country, with some guidelines recommending LDL‐C apheresis as first‐line treatment in patients with homozygous FH and after drug therapy failure in patients with heterozygous FH. Additionally, guidelines typically recommended weekly or biweekly LDL‐C apheresis treatments conducted at apheresis centers that may last 2 to >3 hours per session. Studies reported a range for mean LDL‐C reduction after apheresis: 57–75% for patients with homozygous FH and 58–63% for patients with heterozygous FH. Calculated annual costs (in US$2015) may reach US$66 374 to US$228 956 per patient for weekly treatment.Conclusions LDL‐C apheresis treatment may be necessary for patients with FH when drug therapy is inadequate in reducing LDL‐C to target levels. While apheresis reduces LDL‐C, high per‐session costs and the frequency of guideline‐recommended treatment result in substantial annual costs, which are barriers to the optimal treatment of FH.

Absence of Viral Complications When Using Rituximab to Treat TTP with Plasma Exchange

INTRODUCTIONRituximab is widely used for the treatment of B cell lymphoma and, increasingly, for therapy in autoimmune diseases including TTP. One of the major concerns about this drug is that selectively depleting B-lymphocytes may increase the number of infections with reactivation of latent viruses such has Hepatitis B and Cytomegalovirus (CMV). Immunosuppression can result in increased susceptibility for HEV infection and chronic hepatitis. We have recently carried out a Phase II study in which Rituximabwas administered to 40 TTP patients with relapsing or refractory disease. These patients received very large volumes of non-inactivated plasma (range 50 to 110 litres), so it was considered possible that infection could occur. Therefore, we determined the viral status of the patients prior to, and after treatment.METHODSForty patients, 20 refractory and 20 with relapsing TTP, were recruited from 4 apheresis centres. Each received 375 mg/m2 of Rituximab once a week for 4 weeks. Plasma exchange was initiated on day 0 and carried out daily for at least 7 of 10 days. Response to therapy was measured by platelet count. Tests for viral studies for hepatitis B core antigen and hepatitis E (which we recently reported to be transmitted during PE) were carried out at our National Viral Laboratories (location province). All but 1 patient who also got SDP received either cryosupernatant plasma or FFP in combination. Blood samples were taken on day 0 and repeated at 1, 12, 24 and 52 weeks for viral studies.RESULTSAll patients decreased their CD20 values by week 2 and recovered fully by week 24. lgG levels were slightly decreased at week 2 in the relapsed patients but not in the refractory ones, then remained normal throughout testing. Three relapsing patients were strongly positive for anti-HEV at presentation however, the antibodies were all IgM negative ruling out recent infection. The HEV titres did not change during the period of assessment (52 weeks). One refractory patient was positive for anti-HEV lgG at 0 but negative by 4, 12 and 52 weeks. Two patients were weakly positive for anti-HEV. Of these, one refractory case showed a boost in titre at 24 weeks without producing lgM but no HEV RNA was found. At presentation, 3 other patients had borderline anti-HEV positive values.None of the 36 patients tested showed anti-HBc seroconversion for Hepatitis B at any point. Four weakly positive patients became negative.DISCUSSIONRituximab effectively caused immunosuppression in these TTP patients however, in spite of receiving very large volumes of untreated plasma, there was no evidence of overt infection or significant seroconversion except in the one case with an increase in IgG at 6 months.Immunoglobulin levels remained in the normal range in these patients because of the infusion of donor plasma suggesting a protective effect of the plasma and that maintenance of normal immunoglobulin levels through the use of IVIgG may be protective in other patients receiving Rituximab. DisclosuresNo relevant conflicts of interest to declare.

Adverse events of lipoprotein apheresis and immunoadsorption at the Apheresis Center at the University Hospital Dresden

BackgroundLipoprotein apheresis and immunoadsorption methods have a firm place among therapeutic approaches in order to treat disorders of lipoprotein metabolism or anti-body induced diseases. The extracorporeal treatment is associated with adverse effects, we wanted to report the Dresden experience. MethodsIn this study we retrospectively analyzed the adverse events of several lipoprotein apheresis and immunoadsorption methods at the Apheresis Center in Dresden (Germany). We carefully looked into all available documents. The first extracorporeal lipoprotein apheresis was performed in 1990 and the first extracorporeal immunoadsorption was executed in 1995. Throughout the 23 years study period, 10 different methods were employed in treating 268 patients for a total of 25,293 treatments. ResultsAdverse events of varying severity occurred in 1948 of the treatments (7.7%). We subdivided them into mild (61.3% no treatment was necessary), moderate (37.0% oral medication or infusion was given) and severe (1.7% emergency hospitalization was necessary). Therapy had to be stopped prematurely in 1.5% of the treatments. We compared adverse events profiles among the different methods and evaluated for differences by gender. Females were found to have a significantly higher risk of adverse events than male patients. In males, the rate of adverse events ranged from 3.3% (Liposorber® D) to 11% (Therasorb™ Ig); in females the minimum rate was 7.8% (DALI) and the maximum 30% (rheopheresis). Adverse events were evenly distributed between the ages of 30–69, the age range at which most of the therapies were performed. We also found that all methods had a higher rate of adverse events during the first year of treatment. Puncture problems and hypotension were the most common adverse events. ConclusionIt can be stressed that in general the extracorporeal methods used can be regarded as safe.

First data from the German Lipoprotein Apheresis Registry (GLAR)

ObjectiveIn recent years the Federal Joint Committee (G-BA), a paramount decision-making body of the German health care system challenged the approval of diagnostic and therapeutic procedures for regular reimbursement, including lipoprotein apheresis therapy. Years before an interdisciplinary German apheresis working group, established by members of both German Societies of Nephrology (Verband Deutsche Nierenzentren (VDN), Deutsche Gesellschaft für Nephrologie (DGfN)), initiated a revision of the indication of lipoprotein apheresis therapy according to current guidelines and recommendations for the treatment of lipid disorders. This working group was convinced, that data derived from a registry would support lipoprotein apheresis as a therapy for severe hyperlipidemic patients suffering from progressive cardiovascular diseases. Methods and resultsIn 2009 the working group established the indication for lipoprotein apheresis with respect to current cardiovascular guidelines and scientific knowledge for the registry, which are in line with the reimbursement guidelines. In 2011 financing by sponsors was secured and an internet-based registry was created. A pilot project with 5 apheresis centers finished in 2012 – since then the registry is available to all German apheresis centers. ConclusionsThere has been consensus between the medical societies and health care carriers regarding the need for a German Lipoprotein Apheresis Registry (GLAR). The launch of this registry complies with requirements of the Federal Joint Committee (G-BA). Complementing the Pro(a)LiFe-Study, first data from GLAR support the safety of the different apheresis treatment procedures. In addition these first data suggest, with respect to the results of Pro(a)LiFe-Study, effectiveness in preventing cardiovascular progression as well. Here, further data are needed to statistically substantiate these early findings.

Effects of Lipoprotein apheresis on the Lipoprotein(a) levels in the long run

BackgroundLipoprotein(a) (Lp(a)) is a low density lipoprotein-like particle to which apolipoprotein(a) is bound. It is recognized as an atherosclerosis-inducing risk factor. Up to now a detailed description of the effect of Lipoprotein apheresis (LA) on Lp(a) levels in the long run is lacking. MethodsWe studied 59 patients with elevated Lp(a) levels who were treated with LA at the Lipoprotein Apheresis Center at the University Hospital Dresden. We analyzed Lp(a) concentrations before the start of the LA treatment and during this extracorporeal therapy. ResultsComparing the Lp(a) levels before the start of LA therapy and pre-apheresis (measured before the LA sessions) Lp(a) levels, we observed a reduction of the Lp(a) levels of about 22.8% in all patients. Lp(a) levels were acutely (comparing post-apheresis with pre-apheresis concentrations) reduced by all 6 available LA methods (by about 70%). A linear regression analysis was performed to differentiate the long term course of pre-apheresis Lp(a) levels. In 30 patients we saw an increase of the pre-apheresis Lp(a) levels over the time, in 15 patients a constancy and in 14 patients a decrease. Patients with a decrease of pre-apheresis Lp(a) levels over the time had significantly higher initial (before the start of the extracorporeal treatment) and pre-apheresis values and they were significantly older. These patients had significantly more severe peripheral arterial disease as well as cardiac valve and carotid stenosis. The patients with the lowest initial Lp(a) levels and an increase of the pre-apheresis Lp(a) levels over the time had the highest percentage of intake of Tredaptive®/Niaspan® though after stopping the intake of these nicotinic acid preparations no clear increase of Lp(a) concentrations was observed. The applied LA systems did not seem to have a significant influence on the course of pre-apheresis Lp(a) levels. In all patients there was a high variability of Lp(a) concentrations between LA sessions which may in part be due to the inaccuracy of the method used to measure Lp(a) concentrations. ConclusionPre-apheresis Lp(a) levels (before the LA sessions) are lower than those before the start of a LA treatment but they behave differently among patients during LA treatment.

Impact of the German Lipoprotein Apheresis Registry (DLAR) on therapeutic options to reduce increased Lp(a) levels.

BackgroundThe German Lipoprotein Apheresis Registry (DLAR) has been initiated by members of the Nephrology Foundation (WiNe), the German association of kidney centres (DN), the German society of nephrology (DGfN) and additional medical associations taking part in the apheresis working group. Its goal is the introduction of a substantial database, suitable to provide statistical evidence for the assessment of extracorporeal procedures. Data have been added to the DLAR since October 2011. In this article, preliminary results are first reported.Methods and resultsData are stored on a secured Internet platform. The recorded information comprises mean values and rates of change in lipid levels (cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, lipoprotein(a) (Lp(a)) before and after apheresis therapy, blood/plasma volume, frequency and type of adverse effects, medication, vascular events, diagnoses and comorbidity. It is collected by participating apheresis centres from all over Germany. Up until October 2014, a total of 7946 lipoprotein apheresis (LA) treatments of 991 patients (787 with documented LDL-C and 688 with documented Lp(a) levels) via 96 medical accounts were documented and analysed. The current share of Lp(a) patients is 50.6 % (Lp(a) ≥ 60 mg/dl; n = 348/688). For both LDL-C and Lp(a), lowering rates exceeding 60 % have been observed. Likely in conjunction with these reduction rates, the preliminary analysis shows a 90 % decline in major adverse coronary events (MACE) as well as a decrease in major adverse non-coronary events (MANCE) by 69 %. As before, good tolerability and low rates of adverse effects (< 3 %) of LA therapy were found.ConclusionsThe available numbers suggest in parts very good response by the participating centres to the DLAR. Unfortunately, there are also centres that have not documented any patients so far or LA treatments at all. The benchmark values for reduction rates in lipoprotein concentration required by the directives of the German Federal Joint Committee (G-BA) have all been met. The decrease in MACE and MANCE rates currently observed is very promising. However, the comparably short runtime of the registry does not allow for high confidence in the current results. Certainly, reliable data will be extractable in the coming years. Given the high interest expressed by European neighbours, the extension of the registry to the European level should be a future goal for the DLAR as well.

Cohn de Laval Award Lectureship: The Science Behind the Success Development of a Continuous Flow Blood Cell Separator

On behalf of Dr. Jeane Hester, I would like to thank everyone in the American Apheresis Society and World Apheresis Society involved with the nomination and presentation of this award. She is truly honored by the recognition of her peers and wishes that she could be here to thank each and every one in person. The reason I am standing here goes back 43 years to July of 1971 when a new ‘crop’ of oncology fellows came to MD Anderson Cancer Center and the Department of Developmental Therapeutics. The chairmen of the department were Emil Frei and Emil J Frereich, with Ken McCredie as the head of the then fledgling apheresis center and I was the tech working in Ken’s research lab. Back then it was somewhat rare to have a female physician in the mix, so word traveled quickly about the tall attractive ‘fellow’ who was winning everyone over with her personality, commitment to her profession and, above all, dedication to her patients. As a fellow, part of the responsibility was to choose a research project and work in the lab in their free time. Several months later this here-to-for phantom Dr. Hester appeared in my lab to discuss where she could work on her project regarding Leukoagglutins in Transfusion. So we began sharing the lab, I used it during the day and she used it at night and occasionally we shared! To paraphrase the last line from Casablanca as Bogart and Claude Rains walk into the night: “This was the beginning of a beautiful friendship”. From that time forward, we worked together on many projects until her retirement from MD Anderson in 1995. The most notable achievement was the development of the first blood cell separators to use disposable channels and all the associated outcomes – the calcium citrate binding incorporated into the software, calcium replacement therapy used during collection, bag parameters for the storage and cryopreservation of cells and optimization of the software for the various procedures. The initial development was accomplished through collaboration with the Biomedical Division of IBM and moving forward she collaborated with GAMBRO COBE and until her 2nd retirement this year with TerumoBCT. The very first 2997 manufactured was called the ‘Genie’ and was donated to Dr. Hester’s Apheresis Unit. It was marketed as the IBM 2997, followed by the next generation – the COBE Spectra. Fast forward 30 years and today, this same blood cell separator is the work horse of apheresis, performing stem cell collections, plasma depletions, plateletpheresis, WBC reductions, and RBC depletions. Like all of us, the Spectra will be retired to make room for a newer model, but the scientific principals established during the development of the continuous flow separators (2990 – 2997 – Spectra) serve as the foundation for the future in apheresis. On a personal note, this award has been a time-traveling experience for Jeane and me. We are back 30+ years where she is drafting the speech and I am preparing the slides of our data. Only back then, it was truly hand-produced 35 mm slides and at least now I have the modern technology of PowerPoint. However, several of the slides and photos presented are digitized from the original 35 mm slide. The speech I will be giving has been written by Dr. Hester as if she were here presenting it herself. Many of you who know her will be able to pick up on several of the ‘mantras’ that she often presented and challenged at meetings, such as. . .‘Showme the data’. She is fiercely protective and loving, steadfast when right and can be stubbornly tenacious and I am proud to call her mentor and friend. – April G. Durett, MSc, Manager, Flow Cytometry Facility, Center for Cell & Gene Therapy I will now channel Dr. Hester in Houston, TX, and present her talk. International Forum: from the WAA Congress in San Francisco, 2014. * Corresponding author. Canadian Apheresis Group. E-mail address: cag@cagcanada.ca (G. Rock).

Plateletapheresis in a low-resource center in Nigeria

Introduction: Apheresis is widely established in developed centers but only very few centers in Nigeria have this facility. The commencement of hematopoietic stem cell transplantation (HSCT) in our facility in 2011 necessitated the development of an apheresis center with its enormous benefits for both HSCT patients and other patients in the hospital. Materials and Methods: A retrospective study at the University of Benin Teaching Hospital on donor plateletapheresis over a 4-year period (January 2011 to December 31, 2014). Apheresis machine used for the plateletapheresis is Haemonetics MCS+ and donors were selected using the European Guidelines for apheresis selection. Result: A total of 150 plateletapheresis were performed for 50 patients with an average of 34.75 per annum. Donors were mainly males (84.9%) and the general indication was thrombocytopenia secondary to some medical condition. The main medical indication was thrombocytopenia for patients undergoing HSCT (38.2%). Others were hematological malignancies/chemotherapy-related thrombocytopenia (33.3%) and bone marrow aplasia (7.2%). Sixty-five (46.8%) of donors were of blood group O, 48.2% were of blood group A, 2.2% were of blood group B, and 2.9% were of blood group AB. The majority of the donors (98.6%) were Rhesus-positive. The average number of cycles was 6.4 ± 0.2, average yield was 3.6 ± 0.1 × 10 11 cells, blood volume was 3,135.2 ± 61.0 mL, acid-citrate-dextrose (ACD) was 409.4 ± 25.4 mL, and platelet volume was 243.9 ± 6.1 mL. Conclusion: Plateletapheresis is a new procedure in most developing centers. We have reported the activities in a single center with enormous benefits to patients with thrombocytopenia. There is a need to improve and subsidize these services to make it readily available to patients who require single platelet concentrate.

Prediction of Hematopoietic Stem Cell Yield after Mobilization with GCSF in Healthy Unrelated Donors

Introduction:The collection of hematopoietic stem cells from the peripheral blood in healthy donors has been established as a highly efficient method in clinical practice. Nevertheless, there are some donors who mobilize poorly despite adequate mobilization regimes. Several factors influencing the process of stem cell mobilization have previously been discussed in the literature.Methods:In total, the data of 7.216 unrelated donors who underwent GCSF-induced stem cell mobilization and collection in two German apheresis centers between July 1997 and August 2012 were retrospectively reviewed. We systematically analyzed more than 30 factors with potential influence on the mobilization process and established a statistically stable model in order to predict the mobilization efficacy and the harvest success in unrelated stem cell donors.Based on empirical data and standard values, we created three model donors of each gender with different donor profiles (favorable/average/unfavorable). In those model donors we calculated the corresponding likelihood of a successful stem cell harvest dependent on the recipient’s weight.Results:Overall, ten variables with high statistical significance were included in the prediction model. Body mass index, platelet count, absolute lymphocyte count and the relative monocyte count correlated positively with the CD34+ count in the peripheral blood after five days of GCSF use (p < 0.0001 in a multivariate analysis). In contrast, female sex, age, smoking, lactate dehydrogenase (ldh), relative monocyte count, and the relative large unstained cell count were associated negatively with the CD34+ count on day five (p < 0.0001 in a multivariate analysis).In order to predict the harvest success (collection of > 2 x 10^6 CD34+ cells/kg recipient weight after first apheresis) three different models were compared in a ROC-analysis. The first model was purely based on female sex and recipient weight. The second model additionally contained the predicted CD34+ counts. Finally, in the third model the actual observed CD34+ counts were included.By adding the predicted CD34+ counts to the simple model, a significant improvement of the predictability of a harvest success could be viewed although a considerable difference comparing these results to the model with the observed CD34+ counts remained (figure 1).Furthermore, the prediction of harvest success in model donors (figure 2) revealed that donors with a favorable donor profile (covariates set to the most favorable values within the normal range) showed a particular high likelihood for a successful harvest (100 % likelihood, irrespective to donor’s gender or recipient’s weight). The likelihood for a successful harvest in male donors with an average distribution of covariates (covariates set to the empirical mean value) was nearly 100% as well even in donations for heavy recipients. Contrary, the likelihood for an average female donor was high in normal weight recipients (97 %; 60 kg recipient) but decreased with rising recipient weight (78 %; 140 kg recipient).In donors with an unfavorable profile (covariates set to the worst values within the normal range), especially in females, the chance for a successful stem cell collection was poor even when donating for light recipients (54 % in males, 10 % in females; 60 kg recipient).Conclusions:In conclusion, multiple factors with influence on the CD34+ count after GCSF mobilization in healthy donors have been identified. With the prediction model a significant gain in the predictability of a harvest success could be achieved though a certain amount of unexplained variance still remains.Model donors with a favorable or average donor profile had a high likelihood for a successful stem cell collection. In donors with an unfavorable profile, especially in females, the chance for a harvest success was very low. [Display omitted] Abb.: AUC – area under the curve [Display omitted] DisclosuresSchmidt:Cellex GmbH: Employment. Ehninger:Cellex GmbH: Equity Ownership. Off Label Use: G-CSF.

Lipoprotein apheresis: an update

Since the 1980s, several lipoprotein apheresis methods that eliminate atherogenic lipoproteins (LDL and lipoprotein(a) [Lp(a)]) have been developed. These methods are based on the following principles: precipitation, adsorption and filtration. In Dresden (Germany), we started to perform extracorporeal treatment in 1990; in the 1980s we were working as a lipidologic center and saw patients dying due to severe atherosclerotic diseases. At present, 80 patients are being treated with six different methods at the Apheresis center at the University Hospital Dresden. The effectiveness of these methods with respect to lowering of LDL cholesterol and Lp(a) is somewhat different. The number of patients with high Lp(a) levels and with severe atherosclerotic complications has increased steadily since 2008. Several studies have shown a high effectiveness for apheresis treatment in these patients. In the future, new drugs (e.g., lomitapide, mipomersen or PCSK9 inhibitors) will probably modify the position of apheresis in the therapeutic regimen.

Lipoprotein apheresis standard for apheresis competence centers – An updated synthesis and amendment to pre-existing standards

With several techniques of selective apheresis treatment, some of which have been established for over 30 years, severe and pharmacologically unmanageable dyslipidemia can be treated successfully. The long-term lowering of LDL cholesterol and lipoprotein(a) by 60–80 percent, together with pleiotropic effects, allow for significant risk reduction in otherwise progressive chronic atherosclerotic disease, i.e. chronic coronary artery disease in most apheresis patients, and improvement of quality of life. For various reasons, worldwide only an estimated 2500 patients, among them 1400 to 1500 in Germany, are regularly treated by apheresis. This relatively small number of apheresis patients in Germany is being cared for in more than 200 centers, by more than 750 physicians approved for extracorporeal treatment, resulting in unraveling of expertise and diversity of treatment strategies instead of the needed concentration.Here we present a comprehensive standard for competence centers in apheresis treatment, which is an updated synthesis and amendment to previously published standards, based on the experience from more than 30,000 apheresis treatments in our own center. The presented standard provides a guideline for apheresis treatments, comprising all procedures, indications, detailing the application procedure, as well as suggestions for supportive care in extracorporeal therapy. In the absence of large studies of sufficient quality, this standard represents our “good clinical practice” and refers the “best available evidence”, providing the indispensable basis for working in an apheresis center. The apheresis standard also aims to contribute to quality assurance, another intention is to increase the acceptance of this valuable treatment, with a view to admitting more patients in need to apheresis programs, on the basis of reliable cost reimbursement.

Homocysteine in lipoprotein apheresis patients – Retrospective data analysis in apheresis center of a university hospital

IntroductionThere is an obvious contrast between the data from the epidemiological studies on hyperhomocysteinemia and the negative results of the homocysteine-lowering clinical trials. Moderate hyperhomocysteinemia might only be relevant in certain subgroups of subjects. The current study was focused on lipoprotein apheresis patients; the study goals were to determine the prevalence of hyperhomocysteinemia, to identify the association between homocysteine levels and cardiovascular events and to test the effects of lipoprotein apheresis and of the conventional homocysteine-lowering therapy. Materials and methodsSixty patients from our Lipoprotein Apheresis Center (37 males, 23 females, age 63.1 ± 10.8 years) were included in the study. All patients' records were reviewed with respect to age, sex, BMI, dyslipidemias, arterial hypertension, diabetes mellitus and incidence of vascular events in coronaries, carotids and lower extremities. Homocysteine was measured before and immediately after the apheresis procedure. We also observed the effects of conventional homocysteine-lowering therapy. ResultsThe prevalence of hyperhomocysteinemia was 50%. Homocysteine levels correlated positively with number of cardiovascular events (p < 0.03) and serum creatinine (p < 0.0001) and negatively with serum HDL-cholesterol (p < 0.03). Neither oral nor intravenous medication with vitamin B and folic acid showed a significant homocysteine lowering effect. The median relative change value of homocysteine after apheresis session was −12% but was not statistically significant. ConclusionsThe prevalence of hyperhomocysteinemia in lipoprotein apheresis patients is high. Neither apheresis nor more conventional methods appear to markedly influence homocysteine serum levels.

Iron deficiency and its management in patients undergoing lipoprotein apheresis. Comparison of two parenteral iron formulations

ObjectivesThere is evidence of iron deficiency (ID) in patients treated with lipoprotein apheresis. Aim of this study was to assess ID in apheresis patients and to study its management comparing safety and efficacy of two approved intravenous (i.v.) iron formulations. MethodsInclusion criteria were defined as a) serum ferritin < 300 μg/l and transferrin saturation < 20%, b) ferritin < 100 μg/l. Both iron deficient alone and ID anemic (IDA) patients were included. Other causes for anemia were ruled out by thorough history-taking and examination/blood tests. Patients were treated with six different lipoprotein apheresis methods: DALI, Liposorber D, TheraSorb LDL, HELP, MONET and Lipidfiltration. 50 patients were randomized to either ferric carboxymaltose (FCM, 500–1000 mg as single shot infusion over 20 min) or ferric gluconate (FG, 62.5 mg once weekly). Results50 of 67 patients of our Lipoprotein Apheresis Center showed iron deficiency. Both i.v. iron formulations studied were equally safe (no serious adverse events (SAEs), 6 patients/group showed adverse events (AEs)) and both effective (clinically and with respect to laboratory data) in lipoprotein apheresis patients, however FCM led to a more rapid and steeper rise of iron parameters. ConclusionsID and IDA are common findings in lipoprotein apheresis patients. The pathogenesis remains yet poorly understood and is probably multifactorial. Differential diagnosis of ID/IDA is as essential as differential therapy. Handled with care, older i.v. iron preparations like FG appear to be safe and effective in lipoprotein apheresis patients. However, novel formulations like FCM can be administered rapidly at higher doses due to high complex stability, allowing faster filling of iron stores.Newer laboratory parameters (Reticulocyte-He, low/medium/high fluorescence reticulocytes (LFR/MFR/HFR)) assessing iron status may be helpful in early detection of ID and in monitoring iron replacement therapy.

Why an Apheresis Center Should Offer More Than One Lipoprotein Apheresis Method

We describe our experience with the performance of six lipoprotein apheresis methods (HELP, TheraSorb LDL, DALI, lipidfiltration, Liposorber D, MONET) which have been used in 68 patients. Thirty-four of them have been treated with more than one method. The calculations presented in this paper are based on laboratory data measured at the last three available apheresis sessions before the switch to another method and at the end of the observation period, respectively. With respect to the reduction of low-density lipoprotein (LDL) cholesterol, DALI and Liposorber D appeared to be the most effective lipoprotein apheresis methods, for reduction of lipoprotein(a), Liposorber D. Data on the influence of these lipoprotein apheresis methods on parameters of the coagulation system (prothrombin time, international normalized ratio, activated partial thromboplastin time, fibrinogen) are also reported. The histories of three patients who have been switched to several lipoprotein apheresis methods are given as examples. The major reason for switching was the low efficiency of a given lipoprotein apheresis method with respect to lowering of LDL cholesterol; the reason for this phenomenon was not clear in each case. In three patients who took an oral anticoagulant and were treated with HELP, the influence on the coagulation system is reported; they were submitted to another apheresis method. In two patients we observed an allergy to heparin-they were then treated with a heparin-free apheresis method. In conclusion, we point out that there are several reasons why an apheresis center should offer more than one lipoprotein apheresis method.

Screening of related donors and peripheral blood stem cell collection practices at different Italian apheresis centres.

Recommendations on eligibility criteria for donation of haematopoietic stem cells, management of collection of the cells and follow-up mainly concern unrelated donors. The aim of this study was to analyse the screening of related donors and collection practices at different Italian apheresis centres. A questionnaire regarding eligibility criteria for related haematopoietic stem cell donors, their peripheral blood collections and early follow-up was sent to several apheresis units. Data from the full charts of 500 candidates, screened between May 2005 and December 2009, were retrospectively evaluated. The donors' records, eligibility criteria, collections and follow-up are managed differently in each centre. Of the 500 evaluable candidates (51.2% male, 49.8% female; median age 47 years, range 13-77), 26.4% underwent thorough screening according to Italian Bone Marrow Donor Registry standards, while local protocols were applied to 73.6%; 91 candidates (18.2%) proved ineligible for donation. In the end, 352 donors (53.4% male, 46.6% female; median age 45 years, range 16-76) underwent 508 leukaphereses. Central venous catheters were used in 8.0% of donors, mainly in one centre. Unsuitable pre-apheresis peripheral blood parameters were reported in 38.7% of the aphereses. Leukapheresis-related adverse events were recorded in 23.0% of the procedures, with a drop-out rate of 0.2% for severe events. No donation-related fatalities occurred. The CD34+ cell yield was <2×10(6)/kg of recipient's body weight from 1.1% of donors ≥70 years old. More uniformity in donor screening procedures, management of peripheral blood collection and follow-up should be planned at a national level to maximise the safety of related donors.

An Innovative Approach to Autologous Stem Cell Collection in the Pediatric Patient

Autologous stem cell collection in the pediatric patient can be a challenging and expensive endeavor. Our institution has created a novel, systematic procedure that has created a safe and efficient collection. Using outpatient Interventional Radiology, we place two turbo flow PICC lines with imaging –guided percutaneous technique centrally in patients that are greater than 30 kg. In patients under 30 kg, we are able to use double lumen broviacs or a single turbo flow PICC and the existing central line (I.e. single lumen mediport or broviac). Collection then takes place in our outpatient Apheresis Center without sedation of the patient. We have successfully collected more than 54 pediatric patients, with differing diagnoses, using these methods since the end of September 2008. We have had no documented line infections of the temporary PICC lines. This method allows for the pediatric patient to remain an outpatient, with a low morbidity procedure, but optimizing the stem cell collection process.