Therapeutic apheresis is an important treatment modality frequently used to manage specific complications in patients with underlying malignant disease. Ray Paul. Dark Shadows, 2010. Acrylic, latex, enamel on canvas, 30" × 30". Therapeutic Apheresis for Patients With Cancer Laura S. Connelly-Smith, MBBCh, DM, and Michael L. Linenberger, MD Background: Disease complications associated with certain malignancies may be mediated by cells or soluble molecules that traffic in the bloodstream. Because of this, therapeutic apheresis (TA) methodologies have been used to selectively remove or manipulate specific molecules, antibodies, or cellular elements to treat the underlying pathological process. For some disorders, TA is utilized as a rapid-acting and short-term adjunct to conventional chemotherapy or immunotherapy. For others, a series of scheduled treatments is recommended for optimal management. In all cases, the risks, benefits, and costs must be strongly considered. Methods: The current literature and published guidelines were reviewed to summarize the use of TA in the management of certain complications of cancer. Results: Although TA is relatively safe and useful as a first-line or salvage modality for some disorders, few prospective, randomized clinical trials exist and the majority of evidence is derived from observational studies. Expert-based, clinical practice guidelines have been developed to inform hematology/oncology professionals and apheresis physicians about the efficacy and limitations of TA for malignancy-related indications. Conclusions: Certain oncological conditions respond to TA and consensus guidelines are available to support clinical decision-making. However, well-designed, prospective intervention trials are needed to better define the role of TA for a variety of disorders. Introduction In general, TA is a relatively safe procedure; however, Therapeutic apheresis (TA) is used to treat certain insufficient clinical evidence to support the econom- disease complications in patients with cancer with ic cost of TA can be a limitation to its use for some the intention of removing or manipulating a specific conditions. Evidence-based clinical practice guidelines molecule, antibody, or cellular element thought to be have been developed and periodically updated by the contributing to the underlying pathological process. American Society for Apheresis (ASFA) to help sup- port the decision making of health care professionals regarding the use of TA.1 From the Seattle Cancer Care Alliance (LSC-S, MLL), the Division of In this article, we provide a brief overview of TA Hematology (LSC-S, MLL) of the School of Medicine at the University of Washington, and the Fred Hutchinson Cancer Research Center and discuss considerations for its use as a treatment (MLL), Seattle, Washington. option. The apheresis modalities most commonly Address correspondence to Laura S. Connelly-Smith, MBBCh, DM, used to treat patients with cancer include the ther- Seattle Cancer Care Alliance, 825 East Eastlake Avenue, Seattle, WA, apeutic plasma exchange (TPE), leukocytapheresis, 98109. E-mail: [email protected] extracorporeal photopheresis (ECP), thrombocyta- Submitted June 15, 2014; accepted October 8, 2014. pheresis, and erythrocytapheresis. Herein, we review No significant relationships exist between the authors and the companies/organizations whose products or services may be the known oncological diseases or associations for referenced in this article. which specific TA modalities have been successfully 60 Cancer Control January 2015, Vol. 22, No. 1 Table 1. — Indications for Therapeutic Apheresis in Patients With Cancer Therapeutic Indication Disease Condition Categorya Gradeb Apheresis Modality Therapeutic plasma Hyperviscosity in Symptomatic I 1B exchange (TPE) monoclonal gammopathies Prophylaxis for rituximab I 1C Myeloma kidney/myeloma cast nephropathy II 2B Paraneoplastic neurological syndromes Lambert Eaton myasthenic syndrome II 2C (see also Table 4) Other paraneoplastic III 2C neurological syndromes Hematopoietic stem cell transplantation– Refractory III 2C associated thrombotic microangiopathy Therapeutic Hyperleukocytosis With leukostasis clinical signs I 1B leukocytapheresis and symptoms Prophylaxis (asymptomatic) III 2C Extracorporeal Cutaneous T-cell lymphoma, Erythrodermic I 1B photopheresis mycosis fungoides, Sézary syndrome Nonerythrodermic III 2C GVHD Skin chronic GVHD II 1B Skin acute GVHD II 1C Non–skin acute and chronic GVHD III 2B Thrombocytapheresis Thrombocytosis with Symptomatic II 2C myeloproliferative neoplasm Prophylactic III 2C Erythrocytapheresis Polycythemia vera/primary erythrocytosis I 1B aDenotes American Society for Apheresis category. bDenotes American Society for Apheresis grade. For more information, refer to Tables 2 and 3. GVHD = graft-vs-host disease. Data from reference 1. employed. Table 1 summarizes these modalities, clin- anticoagulated blood during the procedure. The fluid ical conditions, and the most recent ASFA guideline returned back to the patient contains the undesired recommendations.1 However, well-designed, prospec- blood components along with anticoagulant, crystal- tive intervention trials are still required to fully define loid, and/or colloid solutions. Membrane filtration the role of TA for many of these disorders. systems separate and collect plasma on a principle TA plays an important role in the management similar to hemodialysis and ultrafiltration, namely of various oncological diseases. It is a procedure in using membranes permeable to high-molecular-weight which blood is separated from a patient, a portion proteins but not cellular elements. The predominant of which is then removed or otherwise manipulated instruments and methodologies used for TA proce- and the remainder is then returned to the patient. TA dures in the United States utilize centrifugation.2 procedures include TPE (in which plasma is replaced with a colloid or crystalloid solution) and modalities Clinical Adverse Events that selectively remove and dispose of plasma solutes TA can be associated with minimal to potentially fa- (plasmapheresis), white blood cells (WBCs; leukocy- tal adverse events, although the overall incidence is tapheresis), or platelets (thrombocytapheresis). ECP relatively low (5%–12%).3 Hypersensitivity reactions is a type of leukocytapheresis procedure whereby the due to plasma or blood product replacement fluid can removed white cells are manipulated prior to being range from urticarial to anaphylactoid-type reactions. reinfused into the patient. Hypocalcemia secondary to citrate anticoagulant can Apheresis procedures can utilize centrifugation to manifest as paresthesia, nausea, vomiting, lighthead- separate blood components into layers within a rapid- edness, and twitching. Hypovolemia due to fluid shifts ly rotating separation chamber based on their relative or vasovagal reaction may manifest as hypotension, density — with red blood cells (RBCs) being the most muscle cramps, and headache. Rare, serious adverse dense, plasma the least dense — and intermediate events requiring the procedure to be interrupted or layers, moving from the axis of rotation outward and abandoned (0.8% incidence) or resulting in fatality consisting of platelet-rich plasma, lymphocytes, and (≤ 0.5%) due to cardiovascular events can include granulocytes.1 Specific kits are designed to remove arrhythmia or ischemia, pulmonary edema, pulmo- RBCs or plasma or cells of intermediate density from nary embolism, and respiratory arrest; neurological January 2015, Vol. 22, No. 1 Cancer Control 61 complications can also occur and may include tetany, of peripheral veins compared with CVCs has not been seizures, and cerebrovascular accident.3 Hemorrhage, explained by differences in patient age, sex, the me- thrombosis, and infection are uncommon. The causes dian number of treatments per patient, or the type of death have included respiratory arrest, anaphylaxis, of apheresis procedure.13 Nevertheless, peripheral and catheter-associated sepsis.3 venous access is underutilized in TA procedures and is the access of choice because it is associated with a Vascular Access lower risk of infection relative to CVCs and placement The majority of apheresis procedures are centrifuga- can be done immediately with a low risk of other tion based; therefore, they require withdrawal blood serious complications.10 Complications of peripheral flow rates of 50 to 150 mL/minute.4-7 Peripheral an- cannulation include risk of infection, venous infiltra- tecubital veins that can be cannulated using 16- to tion, patient discomfort, thrombosis and sclerosis of 18-gauge polytetrafluoroethylene- or silicone-coat- veins, and the loss of future venous access. Peripheral ed, dialysis-type steel needles will accommodate vein access for TA is not a viable option in children blood flow rates of 80 mL/minute and is adequate due to their small venous caliber. for centrifugation techniques. By contrast, filtration Peripherally inserted central catheters are too therapies require a blood flow rate of at least 150 to small in caliber (4–5 Fr) to accommodate the neg- 200 mL/minute, which is unsuitable for antecubital ative pressure and blood flow rates required for TA veins.4-7 Other considerations specific to TA include procedures.10 Arteriovenous fistulas and grafts are vi- whether the treatment relies on discontinuous, se- able options for long-term access when the treatment quential blood exchange cycles (1 lumen is sufficient) duration is