Apheresis procedures for the treatment of patients and for the collection of cellular therapy products: A British Society for Haematology guideline

This guideline was compiled according to the British Society of Haematology (BSH) process at [https://b-s-h.org.uk/media/16732/bsh-guidance-development-process-dec-5-18.pdf]. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org and are summarised in Appendix 3 of the full guidance document above. The guideline group was selected to be representative of relevant United Kingdom (UK)-based medical and nursing experts. Systematic literature searches were conducted between January and December 2022 using MEDLINE, OVID PLUS, and EMBASE for publications in English, using the following keywords: plasma exchange, apheresis, exchange transfusion, extracorporeal photopheresis, lipoprotein apheresis, leukocytapheresis, peripheral blood stem cells (PBSC), peripheral blood progenitor cells, Advanced Therapy Medicinal Products (ATMP) and other relevant keywords related to the subsections of this guideline. Any relevant recent publications that came to the attention of the group subsequent to December 2022 were also included, following discussion with the full writing group. Review of the manuscript was performed by the BSH Guidelines Committee Transfusion Task force, the BSH Guidelines Committee, and the Transfusion sounding board of BSH. It was also on the members section of the BSH website for comment. Since the publication of the previous BSH apheresis guideline in 2015,1 there have been a number of changes affecting workload and clinical practice for most apheresis services. First, there has been a steady increase in the use of ATMP such as chimeric antigen receptor T (CAR-T) cells,2 which require apheresis for the procurement of autologous or allogeneic lymphocytes as starting material for manufacture, with most services experiencing increased clinical and regulatory burdens as a consequence. Second, there has been a change in referral patterns for plasma exchange. Autoimmune encephalitides have now emerged as one of the top 10 indications based on steadily increasing evidence for efficacy.3 In contrast, patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (one of the top 10 indications for plasma exchange discussed in the 2015 Guideline) are now less commonly referred. This change is largely due to the results of the PEXIVAS study, which have cast doubts on whether plasma exchange has any impact on overall survival or on renal outcomes in this condition.4 However, a recent UK renal medicine consensus statement still makes a weak recommendation for consideration of plasma exchange in a subset of ANCA vasculitis patients.5 Finally, there is a clear expectation that gene therapy for sickle cell disease (SCD) and related conditions, which has shown promising results in multiple pre-clinical trials,6 will move into routine use in the UK National Health Service (NHS) over the next decade, with a potential increased demand for PBSC collections to provide starting material for manufacture. However, this advancement could come with some associated clinical and logistical challenges such as potential use of single-agent plerixafor for PBSC mobilisation from SCD patients due to the risks of granulocyte-colony stimulating factor (G-CSF)-based PBSC mobilisation in this patient group.7 This 2025 revision of the apheresis guidelines updates advice on managing current and anticipated future demand in the UK NHS. As for the 2015 Guideline, the remit of the current guideline covers all plasma exchange regardless of equipment used, all therapeutic procedures undertaken on cell separators, and any autologous or allogeneic donor apheresis for procurement of cellular therapy products (CTPs) such as haematopoietic progenitor cell apheresis (HPC-A), but excludes apheresis performed for procurement of blood components. The primary objective remains to provide healthcare professionals with clear guidance on the use of clinical apheresis. Plasma exchange is used to treat diseases caused by pathogenic antibodies or other macromolecules found in the plasma, or more rarely by albumin-bound small molecules (drugs or toxins) that remain predominantly intravascular. The use of plasma exchange should be evidence-based, while recognising the difficulty of conducting randomised controlled trials (RCTs) in apheresis medicine and the resultant lack of RCTs for many conditions. The main indications for plasma exchange, with associated published evidence, are well set out in the American Society for Apheresis (ASFA), American Society for Nephrology, and Kidney Disease-Improving Global Outcomes guidelines, and these indications are summarised in Table 1. The ASFA guidelines grade indications as Category I (strong evidence for first-line plasma exchange), Category II (strong evidence for second-line plasma exchange) or Category III (some evidence for second-line plasma exchange). Treat as emergency: aim to initiate apheresis within 4 h of presentation. Daily plasma exchange until platelet count is normal for 3 consecutive days. Treat 150% plasma volume until evidence of response, then reduce to 100% plasma volume. For myasthenic crisis: five exchanges (100% plasma volume) at daily or alternate-day intervals. For stabilisation before thymectomy or other surgery: three to five exchanges at alternate-day intervals; ensure normalisation of fibrinogen before surgery; to facilitate planning, ensure adequate time for recovery between last plasma exchange and surgery. When cryoglobulinaemia is associated with severe clinical manifestations such as skin ulcerations, glomerulonephritis or neuropathy. Five exchanges (100% plasma volume) initially, over approximately 2 weeks, for patients with acute symptoms, for example, digital or limb ischaemia. Maintenance plasma exchange may be indicated along with immunosuppressive medication, particularly for patients at on-going of digital or limb at a by The of a by plasma exchange on the volume of plasma to the plasma the of the between the and and the at which the between these of the of such as by plasma exchange that the volume for is 100% to 150% of the plasma while of the many a of five exchanges at 100% plasma volume at daily or alternate-day for the of more or exchange are and of due to or and In these more are of the 10 most indications in and in before the disease are summarised in Table 1. Maintenance plasma exchange is in for or and for a other indications as discussed in the ASFA plasma exchange may be indicated in that are to therapy or patients are of In such the of exchanges may from 2 to This is by and by levels of the or other objective of the for and related in which plasma is used as the for plasma exchange in the to is the most used In to the blood and also use as for plasma exchange to reduce and blood but this practice is associated with a of of a of with as may also be this is on-going of and is in can be a plasma exchange is performed on patients with a or renal or in renal plasma exchange is performed before surgery. For such fibrinogen levels be a of plasma exchange and plasma may be used as of the may be plasma exchange to fibrinogen levels the recovery of have shown that is and for of time or and this the of the UK apheresis in of the with plasma exchange. For patients for the between plasma exchanges may this is to the overall cell exchange using apheresis is to as or cell exchange. primary use is to reduce the of blood cells in However, there is in using in other clinical as can be used to the cells other the are to reduce In blood is to reduce the of to increase the are three for this can be transfusion, cell exchange and cell exchange. 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procedures require adequate Table 4 for a of are the are for and use should to current BSH for cell exchange in require to be to a or for or can be used for in some for example, in procedures or are may consecutive PBSC mobilisation are as a of adequate stem cell may be to move with for of for procedures and less time on for for patients peripheral blood stem cell and cells collections and can to ensure are in the number of associated with and and for and and of to due to and may require for in use to adequate of with of that have been shown of apheresis are for apheresis. well in for one of apheresis are for and for use with apheresis and to ensure and to ensure over time and reduce risks of and within the medical to of and consideration and for use in cell exchange with provide will on other In and should be based on and is a using with for and and a peripheral should be for using a with for of to the of peripheral in of the is now a routine in apheresis. 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The BSH the the writing of this have a of to the BSH and Task which may be on The following members of the writing group and have of to of the writing group will the writing group any evidence that the strength of the in this document or The document will be by the relevant Task and the literature will be 3 to for any evidence that may have been The document will be and from the BSH current guidelines website are will be published on the BSH guidelines website