Apheresis: the first 30 years

Abstract

The history of apheresis begins 40 years ago with two clinical obstacles in the treatment of acute leukemia – hemorrhage (H+) and infection (I+). Following demonstrations that leukemic granulocytes (PMN) could control I+ and platelets (PLT) present in fresh whole blood provided hemostatic function, centrifugal separation devices were developed to separate and collect transfusible quantities of these cell concentrates from normal donor peripheral blood (PB) and to remove pathologic cells and/or plasma molecules to reduce co-morbidities. The increase in patient PMN/PLT PB cell counts was directly related to the number of cells transfused and inversely related to the blood volume of distribution in the patient, but relationships between the PB counts, I+ control and hemostasis remain incompletely characterized. Ironically, dose-response relationships would be demonstrated most unambiguously in PB stem cell transplant (SCT) transplant therapies in the 1990s where infusions of 2–4 E6 CD34+PB SC/kg would predictably lead to myeloid recovery within 8–10 days. Technologic improvements included procedure automation, predictable PLT concentrate (PC) yields, though predictive equations for PB HSC/Immune cell yields remain to be generated. Responding to observations of PLT transfusion refractoriness, industry developed technology to reduce mononuclear cell (MNC) contamination in PC, thought to be responsible for alloimmunization. Leukoreduction provided another major benefit – reducing the potential for transmission of viral infectious particles in MNC in unmodified PC products. What of the future? The emergence of molecular techniques is clearly leading the way to development of additional clinical strategies in immunotherapy, transplant, gene transduction for patients with malignant, autoimmune and inherited disorders, many of which will utilize currently known, or to-be-identified. PB populations of cells mobilized by pharmacologic-cytokine agents specific for the intended therapy. New technologies, adjuncts to apheresis, are needed for apheresis cell (fresh, stored, or cryopreserved) product washing, purging and immunological isolation of specific populations of MNC/HSC and/or plasma molecules to improve clinical benefit. To participate fully in the opportunities created by basic and disease-oriented research and the biotechnology industry, variables associated with apheresis [and unresolved in current devices] need to be addressed. Of particular importance is the need to generate equations that predict yields of these specialized HSC/MNC cellular products, perhaps utilizing the model shown to predict for PC yields, which integrated donor/patient PB biologic variability with procedure parameters and device efficiency and characterizing the contribution to the final yield of intra-procedure cell mobilization in response to cytokine/chemotherapy priming, [a variable not previously studied] and bone marrow reserve. Though regulatory issues and economics seem to dominate the field currently, donor safety issues and patient needs must not be excluded from the decision-making process. Biostatistical analyses of apheresis products, and evidence-based analyses of treatment outcome data to define clinical efficacy issues will be crucial.