Singh, Nirupama

Abstract Background Sickle cell disease (SCD) is a hemoglobinopathy with limited treatment options. Genetic modification of the patient's own hematopoietic stem cells (HSCs) offers an avenue to curative therapy using the patient's own cells. Many challenges exist in collecting sufficient numbers of starting material for manufacturing, beginning with the pre‐mobilization optimization of the patient to the mobilization, collection, and post‐collection phases. Study Design and Methods A working group within the Cellular Therapy Subcommittee of the American Society for Apheresis Clinical Applications Committee describes the challenges associated with apheresis collection of the starting material for gene therapy (GT) product manufacturing for patients with SCD and discusses potential strategies for overcoming these challenges. Results and Discussion Patients must undergo automated red blood cell exchange (RCE) to lower hemoglobin S in a relatively short window of time before apheresis collection of HSCs. The risks and benefits of transfusion as well as the logistics of providing adequate and appropriate blood products must be considered. Limited agents are available for mobilization of HSCs into the peripheral blood for collection and the timing of administration is short. Each collection cycle consists of RCE followed by at least three mobilization and apheresis collection events in addition to collecting backup cells. More than one cycle is typically needed to collect enough cells for GT drug product manufacturing. Optimization of patient factors and apheresis instrument parameters leads to better collection yields. Early and frequent ongoing coordination with all stakeholders involved is critical to developing personalized treatment plans for patients.

ABSTRACTIn this first annual review article, the American Society for Apheresis (ASFA) Attending Physician Subcommittee (APSc) of the Physicians' Committee (PC) curated key apheresis literature in 2023 and presented their choices for the 10 most seminal apheresis articles. PubMed and OVID search engines were used to identify manuscripts from four topic areas: donor apheresis, therapeutic apheresis, education, and cellular therapy. To further identify seminal criteria, they had to present at least one of the following: novel findings, practice‐altering outcomes, international scope, randomized controlled trial, relevant to current clinical practice, and/or provide evidence for category III or IV indications based on the ASFA ninth special issue of the Guidelines on the Use of Therapeutic Apheresis in Clinical Practice‐Evidence‐Based Approach. Inclusion criteria included: full‐length, peer‐reviewed, English language, and human subjects. Case reports, review articles, and meta‐analyses were excluded.

Background: Allograft dysfunction due to presumed antibody‐mediated rejection (pAMR) is one of the most serious complications of heart transplantation. Combination therapies of high‐dose steroids, intravenous immune globulin, and/or therapeutic plasma exchange (TPE) are often used in this setting. Methods: We performed a 9‐year retrospective review of all episodes of pAMR treated with TPE at our institution. pAMR diagnosis was based on clinical and pathologic findings. Left ventricular ejection fraction (LVEF) was measured at baseline, prior to initiation of TPE, and during the course of treatment. Results: There were 42 patients with 47 episodes of pAMR treated with TPE. The majority of episodes were treated with three TPE; however, eight required only two TPE and five episodes required >3 TPE. All episodes of pAMR had LVEF measured before and after the series of TPEs. The mean pre‐TPE LVEF was 38% compared with a post‐therapy mean LVEF of 50% (P < 0.0001). In 16 episodes of pAMR, for which LVEF was measured following each apheresis, there was significant improvement of allograft function after the first TPE (pre‐TPE mean LVEF of 31% and post‐first TPE mean LVEF of 37%; P = 0.02). Incremental and significant improvement in allograft function continued following each TPE. Changes in human leukocyte antigen‐donor specific antibodies and fibrinogen did not correlate with ejection fraction response. Conclusions: The rapid improvement in allograft function in our patients is most likely due to TPE as other pharmacologic interventions have longer onset. TPE should be considered a first‐line intervention in the setting of pAMR. J. Clin. Apheresis 29:316–321 2014. © 2014 Wiley Periodicals, Inc.