Therapeutic cytapheresis: Continuous flow versus intermittent flow apheresis systems

In this retrospective study, we compared two systems, continuous flow (CF) (COBE Spectra) versus intermittent flow (IF) (Haemonetics V-50, M-30), in performance of therapeutic plateletapheresis (TP: N = 49 each) and therapeutic leukapheresis (TL: N = 29 each). Pre- and post-procedure cell reductions, specificity of removal, volumes removed, and incidence of adverse reactions were compared. Standard procedures with minor modifications, starch with IF only, and 180 minutes blood processing time were used. The CF system had a significantly lower percent reduction of platelets during TP at 43 ± 17% than IF at 53 ± 19%. However, no significant difference was found between CF and IF in percent reduction of white blood cells during TL with 49 ± 16% and 42 ± 14%, respectively. The CF system had significantly less hemoglobin reduction (5 ± 4% vs. 19 ± 9%, respectively) and white blood cell reduction (13 ± 15% vs. 27 ± 17%, respectively) for TP than IF and lower (not significant) hemoglobin reduction (9 ± 8% vs. 12.4 ± 8.2%, respectively) as well as platelet reduction (27 ± 18% vs. 35 ± 19%, respectively) for TL. CF also had significantly less volume removed than IF during TP (559 ± 97 vs. 883 ± 304, respectively) and TL (710 ± 134 vs. 1405 ± 421 ml, respectively). Incidence of reactions was lower for CF than IF during TP (8% vs. 10%, respectively) and during TL (14% vs. 21%, respectively). Using our techniques, we found both the CF and IF flow systems were capable of adequately reducing cell counts for TP and TL; however, IF was significantly better in reducing platelet counts during TP. The CF system was more specific in its cell reductions as indicated by lower hemoglobin reductions, WBC reductions (TP), platelet reductions (TL), and volume removed. Reaction incidence was also lower for the CF system.     

A proposal for sectorial organizing and quality standards in therapeutic apheresis: The therapeutic apheresis unit (TAU) standards

Therapeutic apheresis (TA) includes a wide range of therapeutic procedures based on the separation of blood components and the collection of cells with therapeutic activity or the removal of unwanted plasma or cellular components involved in the etiology of various hematologic, renal, neurological, and medical diseases. The complexity of these interventions requires an organizing model to assure a proper clinical environment, technology, quality requirements, and personnel as well as an active system for outcome monitoring for safety and efficacy. Finally, a structured organizing model may favor the efficiency of the TA unit and economic affordability. Here, we describe the more relevant characteristics of a model of TA standards, named TA unit (TAU) standards, that may help to establish a quality program in units working in the field of TA (shown as supplementary material and available at http://www.ifeit.org/pdf/TAU_Standards_3.0.pdf .     

Therapeutic apheresis: Results from a single center in Turkey.

BACKGROUND: Therapeutic apheresis (TA) is carried out for a broad spectrum of diseases and syndromes. AIM: We retrospectively evaluated the results of therapeutic apheresis (TA) including plasma exchange, therapeutic plateletpheresis, and leukapheresis during 2000-2006. METHODS: A total of 195 procedures were performed in 44 patients (25 male and 19 female, with a mean age of 52+/-15 years). These procedures consist of 165 plasma exchanges, 20 therapeutic plateletpheresis, and 10 leukapheresis. The most common indications were hematological, neurological, and metabolic diseases. Eighty-three percent of plasma exchange, 100% of plateletpheresis and leukapheresis belonged to indication Category I or II, according to the guidelines of the American Society for Apheresis. RESULTS: While hemoglobin levels significantly increased (p<0.05), platelet counts decreased (p<0.005) after plasma exchange. Hematological parameters did not statistically change significantly with leukapheresis (p>0.05). Platelet counts significantly decreased with plateletpheresis (p<0.001). Total complications were detected in 21% of the procedures. Adverse events (AE) were seen in 17% of the procedures. None of the patients died (Grade-IV) from any complication. AEs occurred in 14% (Grade-I), 1% (Grade-II), and 2% (Grade-III) of the procedures. The most common AEs were nausea/vomiting, hypotension, and abdominal pain. CONCLUSION: TA, an important procedure in Transfusion Medicine, is safely carried out in our center in several hematological, neurological, and metabolic diseases which are similar to previous reports.     

Update to the ASFA guidelines on the use of therapeutic apheresis in ANCA-associated vasculitis

Since 1986, the American Society for Apheresis (ASFA) has published practice guidelines on the use of therapeutic apheresis in the Journal of Clinical Apheresis (JCA) Special Issue. Since 2007, updated guidelines have been published every 3 years to reflect current evidence based apheresis practice with the most recent edition (8th) published in 2019. With each edition, the guidelines are reviewed and updated based on any newly published literature since the last review. The PEXIVAS study, an international, randomized controlled trial comparing therapeutic plasma exchange (TPE) vs no TPE and standard vs reduced dose steroid regimen on the primary composite outcome of end stage renal disease or death in patients with ANCA-associated vasculitis (AAV), was published in February 2020. This study represents the largest study on the role of therapeutic apheresis in AAV published to date and prompted the JCA Special Issue Writing Committee to reassess the current AAV fact sheet for updates based on this newly available evidence. This interim fact sheet summarizes current ASFA recommendations for the evidence-based use of therapeutic apheresis in AAV and supersedes the recommendations published in the 2019 guidelines.     

The use of therapeutic apheresis in cardiovascular disease

In the last few years, therapeutic apheresis (TA) has emerged as a valuable treatment option for certain life‐threatening cardiovascular diseases (CVDs) and for all the cardiac dysfunctions caused by autoimmune or metabolic disorders. Besides the well‐established indications for apheresis treatment, such as familial hypercholesterolaemia, hyperviscosity syndrome and thrombotic thrombocytopenic purpura (TTP), we discuss the novel approaches in the therapy of dilated cardiomyopathy, cardiac failure and some specific syndromes of severe dysfunction occurring after heart transplantation. The rationale for using apheresis in such patients is the contribution in immune modulation that this procedure can undoubtedly provide. The clinical course of TTP has dramatically changed, thanks to the introduction of therapeutic plasma exchange. Low‐density lipoprotein apheresis has been extremely efficacious, safe and suitable for lowering cholesterol levels and can be used even for long‐term treatment. In Waldenström macroglobulinaemia and other hyperviscosity syndromes, plasma exchange has demonstrated to be an efficient tool for reducing blood viscosity and the risk of a consequent cardiac dysfunction. However, TA may induce oxidative injury to erythrocytes, making these cells more prone to haemolysis and causing a significant reduction in their half‐life. Ascorbate administration can be useful to lower the levels of hydrogen peroxide and proinflammatory mediators in patients undergoing apheresis. Further data are needed to support this benefit and to test other potential antioxidant therapies. Many of these therapeutic indications need further studies to be definitively approved, but preliminary data are encouraging.     

The Italian registry of pediatric therapeutic apheresis: A report on activity during 2005

The results of the 2005 Survey of the Italian Society for Apheresis and Cell Manipulation (SIdEM) reporting on the pediatric procedures carried out in 18 Italian Apheresis Units are presented here. Utilizing a standardized questionnaire, the survey collected data on techniques, types of blood separators, clinical indications, and adverse events. A total of 1,693 apheresis procedures were carried out in 355 pediatric patients: 219 plasma‐exchange, 291 peripheral blood stem cell collections, 791 extracorporeal photochemotherapy (ECP), 265 LDL‐apheresis, 71 erythro‐exchange, 9 cytoreductive apheresis, 47 immunoadsorption sessions. Adverse events were registered in 94 procedures (5.6%), most of which of mild entity, e.g., insufficient flow rate (50.0%) and symptomatic hypocalcemia (24.4%). Our data indicate that all types of apheresis procedures can be safely carried out in children. ECP, utilized primarily for the treatment of graft versus host disease (GvHD) and rejection of solid organ transplantation, are burgeoning procedures in pediatric patients, whereas plasma exchange, which is a common treatment in adults, is infrequently utilized in pediatric medicine. J. Clin. Apheresis, 2009. © 2008 Wiley‐Liss, Inc.     

Therapeutic apheresis in neurological disorders: a survey of the evidence in support of current category I and II indications for therapeutic plasma exchange

Neurologic disorders constitute the largest group of indications for therapeutic plasma exchange. Although some of the traditional indications are supported by properly designed randomized trials, others are not. This article provides a critical look at the evidence in support of the assignment by ASFA of Category I or II indications to neurologic disorders in its most recent (2007) evaluation of therapeutic apheresis.     

Pediatric apheresis emergencies and urgencies: An update

Urgency and emergency in general, and even more in the pediatric setting, remain a thematic debate not yet fully resolved. The decision to undergo a pediatric patient to an invasive treatment not free from potentially serious side effects like an apheresis procedure should be weighted with great attention. At the moment there is no unanimous consensus about the clinical pictures in which an urgency procedure in pediatrics is indicated. Each center acts according to its own experience and not infrequently to its own fears. Consequently the difficult to draw up an unequivocal shared list of pathologies needing an intervention in urgency/emergency it is confirmed as problematic.We report the experience of a big multidisciplinary hospital that has selected and shared with the specialists of different medical disciplines during the years the pediatric clinical conditions in which an urgent intervention with apheresis technology is indicated.     

Therapeutic plasma exchange in a single center: Ibni Sina experience

BACKGROUND: The number of therapeutic procedures is increasing steadily year by year with growing collaboration of departments other than Hematology. In the aim to demonstrate our single center activity we analyzed our data since four years. METHODS: Between years 1998 and 2001, 658 therapeutic plasma exchange (TPE) procedures were performed on 158 patients. Median age and male/female ratio were 37 (range, 15-87) and 80/78, respectively. Main indications were myastenia gravis (n=55, 34%), TTP (n=13, 8.5%), post ABO mismatched allogeneic hematopoietic cell transplantation aregeneratoric anemia (n=6, 7.5%), progressive systemic sclerosis (n=10, 6.5%), multiple myeloma (n=10, 6.5%), Gullian Barre Syndrome (n=9, 5.9%), multiple sclerosis (n=7, 4.6%), Waldenstr?m Macroglobulinemia (n=5, 3.4%), polymyositis (n=4, 2.7%), sepsis and disseminated intravascular coagulation (n=4, 2.7%). Departments who referred the majority of the patients for TPE were neurology (n=199), hematology (n=153), immunology (n=78), intensive care unit (n=78) and thorax surgery (n=51). RESULTS: The median TPE procedure per patient was 4 (range, 1-50). All the procedures were performed on continuous flow cell separators and median plasma volume processed per cycle was 2471 ml (range 436-5000). The replacement fluids used were 3% hydroxyethylstarch (HES) (24%), 5% albumin (35%), fresh frozen plasma (25%), and HES and albumin (16%). HES was tolerated well even as a sole replacement fluid with acceptable minor side effects. In three patients with progressing hypoalbuminemia HES was replaced or combined with 5% albumin. Close monitoring of serum albumin and fibrinogen levels after repeated procedures is mandatory. CONCLUSION: In our four years of TPE experience we have increased our collaboration with other departments. 3% HES+/-5% Albumin is a feasible, well tolerated and cost effective replacement fluid combination especially for short-term plasma exchange therapy.     

The tipping point: The critical role of therapeutic apheresis in a case of refractory acquired hemophilia

Acquired hemophilia A (AHA) is a rare autoimmune disorder that leads to factor VIII (FVIII) deficiency via autoantibody formation. Standard treatment options include FVIII bypassing factors and immunosuppression. However, the role of therapeutic plasma exchange (TPE) is not clear in the treatment of AHA. We present a case of idiopathic AHA in a 66 year old female with severe bleeding and a FVIII inhibitor of 17.6 Bethesda units (BU). She failed to respond to standard treatment including maximum dose of recombinant FVIIa (rFVIIa), rituximab, and other immunosuppressive agents. Her FVIII inhibitor rapidly increased to 140 BU and FVIII was below 5%. TPE was initiated 3 weeks after admission and her bleeding stabilized after the first treatment and completely stopped after three treatments. Repeat testing revealed increased FVIII to 15% and FVIII inhibitor decreased to 2.0 BU. After an additional TPE treatment, her FVIII increased to 27% and FVIII inhibitor decreased to 0.6 BU and she was discharged without bleeding 40 days after admission. In this case, TPE played a critical role in reducing FVIII inhibitor, which resulted in a recovery of FVIII activity and hemostasis. Therefore, TPE should be initiated early in AHA patients with bleeding and high titer of FVIII inhibitor.     

Therapeutic cytoreduction in a 7-month-old baby with acute leukemia

A 7-month-old girl with acute biphenotypic leukemia [t(4;11)] had accompanying anemia, thrombocytopenia, and a white blood cell count of 535,000/μL with 98% blasts. Before instituting chemotherapy, therapeutic leukapheresis was done to reduce the threat of complications from leukostasis. Using a Cobe Spectra blood cell separator primed with modified blood, we processed 1,395 mL of her blood, removing 201 mL of the buffy coat containing 5.8 × 10¹⁰ white blood cells. This reduced the WBC count to 301,000/μL. Only a single procedure was done, without significant complications. The rationale of this preparatory cytoreduction is discussed critically. Subsequent chemotherapy resulted in a long-lasting remission. © 1992 Wiley-Liss, Inc.     

Therapeutic plasma exchange in non-hematooncological disorders in pediatrics: A single center experience

The use of therapeutic plasma exchange in the pediatric age group is mostly based on retrospective, single-center experiences. The decision to implement apheresis in pediatric patients is usually adopted from the results of studies on adult patients. In order to expand the limited data on pediatric TPE in general and non-hematooncological disorders in particular, we retrospectively evaluated TPE experience in pediatric patients who underwent the procedure for reasons other than hematooncological disorders. A total of 160 sessions in 34 patients (21 females and 13 males) with a median age of 7 (1–17) were analyzed. Most of the patients had sepsis and organ failure (12 patients, 35 procedures). In only one patient (2.9%) with methyl malonic aciduria (MMA) and sepsis, the procedure was terminated due to a grade 3 allergic reaction. Among the study cohort, 4 patients passed away. No patient died due to complications of TPE. The relatively low discontinuation rate and the lack of procedure-related mortality indicate that TPE is generally well tolerated in the pediatric age group similar to the adult population. However, since there are very limited evidence-based data on TPE use, especially in the pediatric age group, retrospective case series may also be helpful for clinicians in the decision-making process.     

WAA apheresis registry in the Czech Republic: Two centers experience

Introduction

Hemaphereses are sophisticated procedures performed for many indications even in severely ill patients. Many authors consider quite necessary to register as many details as possible of treatments with therapeutic apheresis. WAA meets the requirement to compare data with centers not performing apheresis for the same diagnosis. In Czech Republic hemaphereses are used in a broad spectrum of indications. Since the year 2004 data on hemaphereses done in Czech Republic have been registered. In this paper we present a survey of our to date recordings.

Patients and methods

Data of performed therapeutic hemaphereses (plasma exchange, erythrocytapheresis, leukapheresis, thrombocytapheresis, photopheresis, immunopheresis, and rheopheresis) have been entered in WAA registry with many details. We have been evaluated 1289 procedures in 216 patients done in our two centers (center I, center II).

Results

Center I registered 129 procedures in 41 patients, center II 1260 procedures in 175 patients. The patients are divided according to centers specialization (center II has registered 12 long-term treated patients with LDL-apheresis; mean time of therapy 7.1 years and a median of 34 procedures/patient. Side-effects registered in center I and center II were 3.1% and 5.6% of the procedures, respectively. Most frequent side-effects were citrate toxicity, neurovegetative lability, problems with venous access and hypotension. All were easy to treat, no serious events or death occurred.

Conclusions

In Czech Republic hemaphereses are performed in a broad scale of indications and now it is nearly 5 years that data are registered in our two university centers. In 2004 we entered WAA registry because it meets the requirement to compare data with centers that do not perform aphereses for the same diagnosis. This comparison would certainly improve efficacy of the hemapheresis therapy even further. To enter WAA registry is easy, at no expense and without any problems.     

The effect of age on peripheral stem cell mobilization in healthy donors,single center experience

Purpose : Peripheral stem cell transplantation is used as a life‐saving therapeutic option in hematological malignancies. As previously established, most hematological malignancies are seen in the elderly population. Therefore, possible HLA‐identical sibling donors of elderly patients are generally of an advanced age. In this study, we aimed to evaluate the effect of old age on stem cell mobilization and quality in older adult healthy sibling donors. Materials and Methods : Between 2006 and 2014, we evaluated 38 healthy donors aged ≥55 years. The granulocyte‐colony stimulating factor (G‐CSF) analogs were used at a dose of 5 µg/kg/day and administered subcutaneously twice a day for five days. CD34+ cells were estimated in the peripheral blood before collection of the apheresis product. The National Marrow Donor Program selects healthy unrelated donors if they are younger than 60 years. Therefore, we compared the product quality in donors over the age of 60 to that in donors aged 60 years or less. Results : We collected sufficient products from all the donors with one to three apheresis procedures. No serious complication was detected in all donors. Reaching the target CD34+ cell count in one day were detected in 83% of younger and 79% of older donors (P = NS). Collected CD34+ cells x10e6/recipient body weight (kg) was same and 5.1 in the groups (P = NS). There were no correlation between the donor age and these parameters. Conclusion : Healthy donor apheresis in older adults can be performed effectively and possible donors should be evaluated regardless of their age. J. Clin. Apheresis 32:16–20, 2017. © 2016 Wiley Periodicals, Inc.