The world apheresis association registry, 2023 update.

The WAA apheresis registry contains data on more than 140,000 apheresis procedures conducted in 12 different countries. The aim is to give an update of indications, type and number of procedures and adverse events (AEs). MATERIAL AND METHODS: The WAA-registry is used for registration of apheresis procedures and is free of charge. The responsible person for a center can apply at the site www.waa-registry.org RESULTS: Data includes reported AEs from 2012 and various procedures and diagnoses during the years 2018-2022; the latter in total from 27 centers registered a total of 9500 patients (41% women) that began therapeutic apheresis (TA) during the period. A total of 58,355 apheresis procedures were performed. The mean age was 50 years (range 0-94). The most common apheresis procedure was stem cell collection for which multiple myeloma was the most frequent diagnosis (51%). Donor cell collection was done in 14% and plasma exchange (PEX) in 28% of patients; In relation to all performed procedures PEX, using a centrifuge (35%) and LDL-apheresis (20%) were the most common. The main indication for PEX was TTP (17%). Peripheral veins were used in 56% as the vascular access. The preferred anticoagulant was ACD. AEs occurred in 2.7% of all procedures and were mostly mild (1%) and moderate 1.5% (needed supportive medication) and, only rarely, severe (0.15%). CONCLUSION: The data showed a wide range of indications and variability in apheresis procedures with low AE frequency.

[The role of PCSK9-inhibitors and of lipoprotein apheresis in the treatment of homozygous and severe heterozygous familial hypercholesterolemia: A rivalry, or are things quite different?] / Postavení inhibitoru PCSK9 a lipoproteinové aferézy v lécbe homozygotní a závazné heterozygotní familiární hypercholesterolemie: Kdo z koho, nebo je to jinak?

PCSK9-inhibitors belong to the new class of hypolipidemic agents. They enhance catabolism of low density lipoprotein cholesterol (LDL-C) through inhibiting activity of proprotein convertase subtilisin/kexin type 9 (PCSK9). They are monoclonal antibodies (alirocumab, evolocumab etc). Under clinical development are also other types of PCSK9-inhibitors which act at a subcellular level. The treatment with PCSK9-inhibitors can be beneficially combined with lipoprotein apheresis (LA). If such treatment using PCSK9-inhibitors is possible with regard to an individual patients genotype, the combination of LA and PCSK9-inhibitors leads to slowing the space of LDL-C increase between individual procedures of apheresis and enables attaining of the lowest possible values of LDL-cholesterolemia for the longest possible period of time. Due to high efficiency of PCSK9-inhibitors lowering LDL-C, but also their lower cost as compared to therapeutic LA, PCSK9-inhibitors now take precedence over the use of extracorporeal lipoprotein apheresis which, nonetheless, still remains the final method for hypolipidemic treatment of patients with severe hypercholesterolemia, who are resistant to conventional therapy while not reaching the target lipid values and at high cardiovascular risk. They belong to extracorporeal elimination methodologies which remove low density lipoprotein (LDL) cholesterol from circulating blood. LA in combination with higher doses of statins and ezetimib currently represents the most efficient method of treatment of homozygous and statin-refractory heterozygous familial hypercholesterolemia (FH). Residual cardiovascular risk in these patients still remains high, in particular because, despite the aforementioned treatment, the target values for lipids according to present recommendations cannot be reached. The combination of LA with the new drugs is promising, primarily due to its potential for further lowering of LDL-cholesterolemia between the individual apheresis procedures. Preliminary results of the ongoing studies indicate that the new hypolipidemic drugs in combination with LA, or when used separately, will substantially enrich and improve the treatment of refractory FH.Key words: alirocumab - atherosclerosis - evolocumab - hypercholesterolemia - cardiovascular disease - lipoprotein apheresis.

[Position of lipoprotein apheresis in present]. / Postavení lipoproteinové aferézy v soucasnosti.

Lipoprotein apheresis (LA) is an effective treatment method the patients with severe hypercholesterolemia, resistant to the standard therapy. LA is an extracorporeal elimination technique, which specifically removes low density lipoprotein (LDL) cholesterol from the circulation. At present, lipoprotein apheresis, combined with high-dose statin and ezetimibe therapy, is the best available means of treating patients with homozygous and statin refractory heterozygous familial hypercholesterolaemia (FH). However, the extent of cholesterol-lowering achieved is often insufficient to meet the targets set by current guidelines. The recent advent of new classes of lipid-lowering agents provides new hope that the latter objective may now be achievable. These compounds act either by reducing low density lipoprotein (LDL) cholesterol production by inhibiting apolipoprotein B synthesis with an antisense oligonucleotide (mipomersen), or by inhibiting microsomal triglyceride transfer protein (lomitapid), or by enhancing LDL catabolism via monoclonal antibody-mediated inhibition of the activity of proprotein convertase subtilisin/kexin 9 (PCSK9-alirocumab, evolocumab etc). The promising is the combination of LDL-apheresis with new drugs, namely for its potential to further decrease of LDL-cholesterol between apheresis. Depending on the outcome of current trials, it seems likely that these compounds, used alone or combined with lipoprotein apheresis, will markedly improve the management of refractory FH.

[LDL-apheresis in the treatment familial hypercholesterolemia]. / LDL-aferéza v lécbe familiárních hyperlipoproteinemií

LDL-apheresis is an extracorporeal elimination technique, which specifically removes LDL-cholesterol from the circulation. There are six methods for the selective LDL-cholesterol removal these days. The main indications for LDL-apheresis are the diagnosis of homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia which is refractory the standard care and intolerance of routine care, and also patients with lipoprotein(a) increase resistant to the farmacotherapy. There is still debate which LDL-cholesterolemia is indication for LDL-apheresis therapy, and the recommendation differs among various countries. Despite large randomized trials are missing, there are several good quality studies to conclude, that the beneficial cardiovascular effects of LDL-apheresis in severe hypercholesterolemia are important and beneficial.

Fifteen years of single center experience with stem cell transplantation for multiple myeloma: a retrospective analysis.

INTRODUCTION: Autologous stem cell transplantation (ASCT) became standard of care for patients with multiple myeloma (MM) under the age of 65 years. We routinely perform ASCT for newly diagnosed MM since 1996 in our department. PATIENTS AND METHODS: We retrospectively analyzed all 285 transplants in 185 patients done for MM from January 1996 till December 2010. We analyzed overall survival (OS) and progression-free survival (PFS) regarding conditioning, stage, complete or very good partial remission (CR, VGPR) achievement, renal impairment, single vs. double transplant. RESULTS: Estimated 10-years survival of the whole set of patients is 39% (median survival 95 months). Patients with renal impairment show same OS as those without (p = 0.22). Patients show similar overall survival and event free survival regardless of type of transplant. We observed better outcome in terms of overall survival in patients treated with new drugs (p = 0.0014). Reaching CR or VGPR was not translated into better OS (p = 0.30) and EFS (p = 0.10). Also stage of the disease and whether single or double transplant was used did not make any significant difference in the outcome. CONCLUSION: Stem cell transplantation greatly improved outcome of patients with MM. Poor outcome of allogeneic transplantation in our group of patients is related to high transplant related mortality (20% vs. 0%) and unexpected high relapse rate. There is a trend towards better survival, when new drugs are incorporated at any time in the course of the disease. This fact supports hypothesis that use of these drugs with ASCT should translate into better long-term outcome.

Beneficial effect of plasma exchange in the treatment of toxic epidermal necrolysis: a series of four cases.

INTRODUCTION: Toxic epidermal necrolysis (TEN) is a rare, life-threatening disease with a high mortality rate that is linked to drug toxicity. There is a lack of data about the underlying pathophysiologic mechanisms and treatment options. The only widely accepted treatment of TEN is withdrawal of the offending drug followed by supportive care. The potential roles of corticosteroids, intravenous immunoglobulin (IVIG) and plasmapheresis (TPE) remain controversial. AIMS: We present four patients with severe TEN (all with >80% involvement of body surface) who were treated with TPE following unsuccessful treatment with corticosteroids/IVIG. METHODS: TPE was performed using a COBE Spectra blood cell separator. ACD-A was used as anticoagulant fluid and the target-washed plasma volume was one body volume. Plasma was replaced by a 5% solution of human albumin + Ringer's lactate. RESULTS: The mean number of TPE sessions was 5.25 ± 2.22 (range 3-8). Drugs were implicated as an etiologic agent in each case. TPE led to prompt improvement of acute condition and general health as well as halting of disease progression. Additionally, the restoration of the epithelium began in all four patients. CONCLUSION: Plasmapheresis should be considered as an alternative treatment modality for patients with the most severe form of TEN if initial treatment with other agents, including corticosteroids and/or IVIG, fails. Drugs were suspected to be the cause of TEN in all four cases.

Pregnancy in homozygous familial hypercholesterolemia-A case series.

INTRODUCTION: Familial hypercholesterolemia (FH) is an autosomal codominant lipid metabolism disorder. It results in lifelong elevation of plasmatic low-density lipoprotein cholesterol (LDL-C) levels, followed by premature atherosclerosis. In women, pregnancy and lactation represent an additional risk due to association of physiological changes, pre-existing dyslipidemia, and limited therapeutic possibilities and experiences. Methods of extracorporeal LDL-apheresis represent a suitable therapeutic approach. CASE SERIES: We present our experience in case reports of six HoFH women and their 13 pregnancies (nine successful, three abortions, and one interruption). One patient experienced a lethal complication of her pregnancy. Of the nine successful pregnancies, two cases were treated by LDL-apheresis. CONCLUSION: Pregnancy in HoFH women represents substantial risk; however, patients without signs of decompensated cardiovascular disease can have a good prognosis. LDL-apheresis plays an important role in the management of pregnancy in HoFH.

Experience with extracorporeal elimination therapy in myasthenia gravis.

We describe our experience with plasma exchange (PE) and immunoadsorption in patients with myasthenia gravis. The group of 27 patients consists of 21 patients treated with PE and 6 patients who received immunoadsorption. PE therapy led to stabilization in 20 patients. In patients treated with immunoadsorption, therapy could be discontinued in 2 patients after 13 months of therapy, and the other 4 patients were stabilized without myasthenic crises after 6-9 years of therapy. Extracorporeal elimination therapy through PE or immunoadsorption is effective and sometimes life saving and is safe in the hands of an experienced team (6% complication rate).

Therapeutic Apheresis, Circulating PLD, and Mucocutaneous Toxicity: Our Clinical Experience through Four Years.

Cancer treatment has been greatly improved by the combined use of targeted therapies and novel biotechnological methods. Regarding the former, pegylated liposomal doxorubicin (PLD) has a preferential accumulation within cancer tumors, thus having lower toxicity on healthy cells. PLD has been implemented in the targeted treatment of sarcoma, ovarian, breast, and lung cancer. In comparison with conventional doxorubicin, PLD has lower cardiotoxicity and hematotoxicity; however, PLD can induce mucositis and palmo-plantar erythrodysesthesia (PPE, hand-foot syndrome), which limits its use. Therapeutical apheresis is a clinically proven solution against early PLD toxicity without hindering the efficacy of the treatment. The present review summarizes the pharmacokinetics and pharmacodynamics of PLD and the beneficial effects of extracorporeal apheresis on the incidence of PPE during chemoradiotherapy in cancer patients.

Erratum: Filip, S.; et al. Therapeutic Apheresis, Circulating PLD, and Mucocutaneous Toxicity: Our Clinical Experience through Four Years. Pharmaceutics 2020, 12, 940.

The following correction has been made to this paper [...].

IDH1 and IDH2 mutations in patients with acute myeloid leukemia: Suitable targets for minimal residual disease monitoring?

OBJECTIVES: Molecular screening plays a major role in prognostic categorization and subsequent definition of treatment strategies for acute myeloid leukemia. The possibility of using IDH1/2 mutations as a marker for the monitoring of minimal residual disease (MRD) is still under investigation and remains unclear. METHODS: In this retrospective study, we evaluated 90 patients with de novo AML using Sanger sequencing (exon 4, IDH1 and IDH2). For subsequent MRD monitoring were used both methods, massive parallel sequencing and droplet digital PCR (ddPCR). RESULTS: We identified 22 patients (24%) who harboured mutations in IDH1 or IDH2 genes. Fourteen (64%) of them had other commonly used MRD markers (insertion in NPM1 and partial tandem duplication of MLL, MLL-PTD). Eight of the 22 patients had IDH1 mutations, 13 had IDH2 mutations and 1 had both IDH1 and IDH2 mutations. In our cohort, this IDH1/2 marker responded to the treatment in all of the patients and reflected the onset of the relapse very well. NPM1 mutation based MRD monitoring was more sensitive and predicted relapse earlier but IDH1/2 based monitoring was more sensitive than a method based on MLL-PTD. Both massive parallel sequencing and ddPCR were competent to monitor MRD using IDH1/2. Nevertheless, ddPCR was able to achieve a higher sensitivity in some cases and moreover this method can analyse a single sample without significant price increases. CONCLUSION: Given these data, we conclude that IDH1/2 mutations can be used as a reliable and cost-effective marker for MRD monitoring.

Rheopheresis in treatment of idiopathic sensorineural sudden hearing loss.

BACKROUND: Only few therapeutic options exist for patients with refractory sudden idiopathic sensorineural hearing loss (SISHL). Little is known about the efficacy of second-line therapies. Rheopheresis seems to be an effective therapeutic possibility. METHODS: Between 2012 and 2015, 106 patients with SISHL were enrolled in the study, of whom 52 were refractory to initial treatment. As salvage therapy, these patients were offered either 3 sessions of rheopheresis (33 pts) or intratympanic steroid treatment through MicroWick application (19 pts). Pure tone audiometry was performed at diagnosis, at the 1st month and the 1st year during the follow-up. RESULTS: Patients in the rheopheretic arm had higher hearing loss than in the MicroWick arm (81% vs. 52%, p = 0.04). In spite of this, there was a significant improvement for patients in the rheopheretic arm (27% of hearing loss reduction, p < 0.001) after the 1st month and this remained unchanged during the 1st year, while no improvement was seen in the MicroWick arm (0% of hearing loss reduction, p = 0.424). We found no predictive factor for steroid-failure in first-line therapy. Older age (p = 0.003), presence of vertigo (p = 0.006) and more profound initial hearing loss (p < 0.001) were identified as negative prognostic markers. CONCLUSION: Rheopheresis can be used as a potentially effective and safe salvage therapy for patients with cortico-refractory SISHL.

Preservation of the Photoreceptor Inner/Outer Segment Junction in Dry Age-Related Macular Degeneration Treated by Rheohemapheresis.

Aim. To evaluate the long-term effect of rheohemapheresis (RHF) treatment of age-related macular degeneration (AMD) on photoreceptor IS/OS junction status. Methods. In our study, we followed 24 patients with dry AMD and drusenoid retinal pigment epithelium detachment (DPED) for a period of more than 2.5 years. Twelve patients (22 eyes) were treated by RHF and 12 controls (18 eyes) were randomized. The treated group underwent 8 RHF standardized procedures. We evaluated best-corrected visual acuity, IS/OS junction status (SD OCT), and macular function (multifocal electroretinography) at baseline and at 2.5-year follow-up. Results. RHF caused a decrease of whole-blood viscosity/plasma viscosity at about 15/12%. BCVA of treated patients increased insignificantly (P = 0.187) from median 74.0 letters (56.2 to 81.3 letters) to median 79.0 letters (57.3 to 83.4 letters), but it decreased significantly from 74.0 letters (25.2 to 82.6 letters) to 72.5 letters (23.4 to 83.1 letters) in the control group (P = 0.041). The mfERG responses in the region of eccentricity between 1.8° and 7° were significantly higher in treated patients (P = 0.04). Conclusions. RHF contributed to sparing of photoreceptor IS/OS junction integrity in the fovea, which is assumed to be a predictive factor for preservation of visual acuity.

Blood levels of antioxidants during age-related macular degeneration treatment by rheohaemapheresis.

AIMS: Rheohaemapheresis treatment influences rheological markers and most likely improves metabolism in affected retinal areas, resulting not only in absorption of soft drusen but also reduction or complete disappearance of drusenoid retinal pigment epithelium detachments. However, the character of the treatment process has raised suspicion that there is a decrease not only in cholesterol but also in antioxidants, such as vitamin E and vitamin A. METHODS: Twenty-three patients with the progressive dry form of age-related macular degeneration were each treated with 8 procedures of rheohaemapheresis. We measured levels of vitamin E (α-tocopherol), the vitamin E/cholesterol ratio in serum and lipoproteins (VLDL, LDL, HDL). Vitamin E in erythrocyte membrane and serum vitamin A (retinol) were also measured. These parameters were determined before and after rheohaemapheresis. Erythrocyte superoxide dismutase, erythrocyte glutathione peroxidase and serum malondialdehyde were analysed as markers of antioxidant activity and lipid peroxidation, respectively. RESULTS: In serum, the VLDL and LDL fraction ratios of vitamin E/cholesterol increased significantly. Additionally, the HDL fraction ratio showed an increase but this was not statistically significant. The patients showed no clinical signs of vitamin E deficiency, and their serum concentrations of vitamin E did not differ from normal values. The results show that rheohaemapheresis in addition to causing a significant reduction in atherogenic LDL cholesterol, may have favourable additive anti-atherogenic effects due to a relative increase in the content of vitamin E in the lipoprotein fractions.

The Effect of LDL-Apheresis and Rheohaemapheresis Treatment on Vitamin E.

Lipid apheresis (extracorporeal lipoprotein elimination) is administered to patients with familial hypercholesterolemia who fail to respond to standard therapy. The nature of the treatment process raises the suspicion that it decreases not only cholesterol but also antioxidants. A group of 12 patients (average age 47±17 y, 4 homozygous and 8 heterozygous individuals) with familial hypercholesterolemia treated by LDL-apheresis or rheohaemapheresis for 3-12 y was included in the study. In addition to cholesterol and triacylglycerol levels, vitamin E and vitamin A and also other markers of antioxidant activity were investigated. Nevertheless, the most important determined parameter was the vitamin E/cholesterol ratio in serum and lipoproteins. The results indicate that both extracorporeal elimination methods are effective and suitable ways to treat severe familial hypercholesterolemia, as the LDL fraction of cholesterol decreased by approximately 77% and 66% following LDL-apheresis and rheohaemapheresis, respectively. In addition, the serum vitamin E decreased by 54% and 57% and the decrease of the serum vitamin A was approximately 20%. However, the main marker of antioxidant capacity, vitamin E/cholesterol ratio, in the serum, VLDL and LDL significantly increased. The increase of vitamin E levels in the erythrocyte membranes of 2% following LDL-apheresis and a significant increase of 4% following rheohaemapheresis were confirmed. The presented results indicate that LDL-apheresis and rheohaemapheresis can be considered to be safe procedures according to the antioxidant capacity of the serum, VLDL and LDL lipoprotein fractions and the erythrocyte membrane.

Dynamics of blood count after rheohemapheresis in age-related macular degeneration: possible association with clinical changes.

BACKGROUND: Rheohemapheresis (RHF) is a method that can stop the activity of the dry form of age-related macular degeneration (AMD). The pathophysiologic mechanisms are not well understood, and the effects of the RHF procedures extend beyond the time of the individual procedures. PATIENTS AND METHODS: We present the data for 46 patients with AMD treated with a series of 8 rheohemapheretic procedures. Blood count parameters were measured before the first and the last procedures. The clinical effect was judged by changes in the drusenoid pigment epithelium detachment (DPED) area before and after the rheopheretic sessions. RESULTS: Rheopheresis caused a decrease in hemoglobin (P<0.001), a decrease in leukocytes (P<0.034), and an increase in platelets (P<0.005). We found a negative correlation between the amount of platelets and their volume (P<0.001, Pearson correlation coefficient: -0.509). We identified the platelet/MPV ratio as a good predictor of the clinical outcome. Patients with a platelet/MPV ratio greater than 21.5 (before the last rheopheresis) had a significantly better outcome (P=0.003, sensitivity of 76.9% and specificity of 80%). CONCLUSION: Several basic blood count parameters after RHF can be concluded to significantly change, with some of those changes correlating with the clinical results (reduction of the DPED area).

Long-term outcomes of rheohaemapheresis in the treatment of dry form of age-related macular degeneration.

Purpose. Determining long-term effects of rheohaemapheresis on the dry form of age-related macular degeneration. Methods. This study evaluates 19 patients, average age of 67.6 years, treated with rheohaemapheresis and 18 patients, average age of 72.8 years, comprising the control group. Minimum follow up period was 3.5 years. Each treated patient received a series of 8 sessions of rheohaemapheresis of 1.5 plasma volumes within 10 weeks. We measured the drusenoid pigment epithelium detachment (DPED), best-corrected visual acuity (BCVA), electroretinography (ERG), and rheological parameters. Results. In the treatment group, the baseline BCVA was 0.74 (0.36-1.0) 95% CI and BCVA after 3.5 years was 0.79 (0.41-1.0) 95% CI (P = 0.726). In the control group, the baseline BCVA was 0.71 (0.15-1.0) 95% CI and BCVA after 3.5 years decreased to 0.7 (0.32-0.87) 95% CI (P = 0.031). Baseline DPED was 6.78 ± 3.79 mm(2); after 3.5 years, it decreased to 4.13 ± 3.84 mm(2) (P < 0.001). In the control group, the baseline DPED was 4.09 ± 3.48 mm(2); after 3.5 years, it increased to 6.69 ± 4.2 mm(2) (P = 0.001). We noted increasing levels of positive wave peaking at 50 milliseconds (P50) after treatment (P = 0.022) and a stable amplitude of photopic responses of treated patients. Conclusion. Over the long term, rheohaemapheresis reduced the DPED, improved the function of photoreceptors, and prevented the decline of BCVA.

The importance of rheological parameters in the therapy of the dry form of age-related macular degeneration with rheohaemapheresis.

To date, rheological treatment is the only chance to control the advanced dry form of age-related macular degeneration and arrest its progression to legal blindness. Rheohaemapheresis can change the main rheological parameters, blood and plasma viscosity, as well as change erythrocyte aggregability, improve erythrocyte flexibility and lead to substantial improvement when other methods of therapy fail. In this study, we describe changes in the levels of rheological efficacy indicators after rheohaemapheresis and their clinical significance in the dry form of age-related macular degeneration (AMD). Seventy-two patients with AMD were randomised; 34 controls, and 38 patients were treated with rheohaemapheresis (separator Cobe Spectra + Evaflux filter). After the procedures, α2-macroglobulin levels decreased by approximately 58%, fibrinogen by approximately 65%, IgM by approximately 67%, LDL cholesterol by approximately 71%, apolipoprotein B by approximately 65%, and lipoprotein (a) by approximately 42%. These decreases correspond with a decrease in blood and plasma viscosity (14/12%), clinical improvement (arrest of disease progression, even visual improvement in some cases), and heretofore-unreported improvement (even reattachment) of drusen retinal pigment epithelium detachment. Our modification of rheohaemapheresis is safe (5.4% of patients experienced clinically insignificant side effects).