6/6/2019 Objectives: APHERESIS 1. Discuss Apheresis and key concepts 2. Understand the Apheresis patient population 3. Discuss: ●Cell Collection ●Extracorporeal Photopheresis (ECP) 4. Understand regulatory oversight SCCA Partners Apheresis noun: Greek word meaning to take away Elements Whole blood Separation by removal centrifugation Cells removed, replaced or reinfused 3 6/6/2019 4 6/6/2019 Apheresis Procedures Patient Population – Cell Collections Therapeutic Collection • Photopheresis (ECP) • Stem Cells • Autologous Plasma Exchange • Lymphocytes • PLT Depletion • WBC Depletion Patient Patient Allogeneic Donor Lymphocyte Infusion (DLI) Donor Patient Immunotherapy Patient Patient 1 6/6/2019 Patient Population – ECP Patient Population – Other Therapeutic Indications Cutaneous T-cell Lymphoma Therapeutic Plasma Exchange (TPE) • Mycosis Fungoides • Waldenstrom’s Macroglobulineamia (WM) • Sézary Syndrome • Thrombotic thrombocytopenic purpura (TTP) Graft Versus Host Disease Platelet Depletion • Post Allogeneic Stem Cell Transplant • Thrombocytosis Solid Organ Transplant Rejection WBC Depletion • e.g. Cardiac, Lung • Leukemia Pictured: Jodi Andres’ hand High-Flow Venous Access Two points of access usually required Blood Blood OUT IN Key Concepts Fast flow rates Up to 142 ml/minute Uninterrupted blood flow for 2-6 hours Peripheral Venous Access Central Venous Access Requirements • AV Fistula Needle • Dual-lumen • High-flow, 9.5 - 14 Fr • IV catheter Tunneled: Hickman • Autologous patients • 18g or bigger • ECP • AC veins Non-tunneled: Mahurkar • Allogeneic donors • Limited mobility • Autolougous patients (for storage) • IMTX Implanted Port: Vortex or BARD PowerFlow • ECP 2 6/6/2019 Extracorporeal Volume (ECV) Separation by Centrifugation • ECV = amount of whole blood in the Apheresis circuit • Average 250mL • Can be as much at 450mLs with some circuits • Regulations prohibit removing > 15% of total blood volume • One size circuit, but may not fit all bodies • ECV impacts patient oxygenation Separation by Centrifugation Anticoagulation ACD-A Heparin (anticoagulant citrate dextrose, formula A) • Binds ionized calcium • Inactivates thrombin and ± 1.040 1% muscles, blood Factor Xa PLASMA Blood: ¼ is ionized BUFFY COAT 1.050 – 1.061 SPECIFIC BUFFY COAT GRAVITY 1.065 – 1.060 99% Bones PACKED RBCs Calcium 1.087 – 1.092 • Side-effects: Ca, K, Mg • Systemic anticoagulation • Short-acting • Long-acting Side Effects Citrate Toxicity • Citrate toxicity Feels like: • Lips tingling, body vibration, cramps, chest pain • Vasovagal reaction Looks like: • Bleeding • Low ionized calcium, pallor, tetany • Blood loss Management: • Transfusion needs • Pause the procedure – resume using slower flow rate • Allergic reactions (ETO) • Oral replacement – TUMS, calcium-rich food • IV replacement – calcium gluconate • Fatigue 3 6/6/2019 Pediatric Population Small body, big circuit • Prime the apheresis circuit with packed RBCs Side-effects are subtle, fast and strong Cell Collections IV access • Usually central • Peripheral access is possible in larger children (40-50 kg) when patient is highly motivated Patient Population – Cell Collections Road Map ④ Collection Autologous Patient Patient ③ Mobilization Allogeneic ② Vascular Assessment/ Donor Lymphocyte Patient Education Infusion (DLI) Donor Patient Immunotherapy Patient Patient ① Work up Work Up Patient Education All Collections Allogeneic/DLI • Hydrate, hydrate, hydrate! • Consent • Recipient Compatibility • H&P • Pregnancy Testing pre-GCSF • Infectious Disease Testing • Donor History • Calcium-rich food • ABO Typing Questionnaire • Venous Assessment • Donor Eligibility Declaration • Hematologic Considerations • HCT, PLTs Autologous • Stay warm • Storage Contract • Bring entertainment 4 6/6/2019 Mobilization Timing Stem cells are moved from bone marrow to blood circulation Protocol driven allowing stem cells to be collected from peripheral blood Autologous collection trigger • 4th day of G-CSF mobilization • Peripheral CD34 level (PBL) > 20 uL Allogeneic collection trigger • 4th day of G-CSF mobilization Autologous Allogeneic Donors • Chemotherapy + G-CSF • G-CSF Donor Lymphocyte Infusion • G-CSF • Situation dependent • Plerixifor (Mozobil) Leukapheresis Collection Goals Protocol and diagnosis driven Lymphocytes/Stem Cells collected in bag Autologous targets • Myeloma: 10 x 106 CD34+/kg Lymphocytes/ 6 + WB in • NHL: 5 x 10 CD34 / kg Stem Cells out Blood minus collected cells returned to Allogeneic targets patient • Typically 5 x 106 CD34+/ kg recipient weight • 1-2 days of collection Whole blood (WB) removed IMTX Targets from patient • Protocol specific • Usually one day of collection Patient Population – ECP Cutaneous T-cell Lymphoma • Mycosis Fungoides Extracorporeal Photopheresis • Sézary Syndrome (ECP) Graft Versus Host Disease • Post Allogeneic Stem Cell Transplant Solid Organ Transplant Rejection • e.g. Cardiac, Lung 5 6/6/2019 Road Map Work-up ④ Treatment • Financial Clearance Trajectory • Consent • H&P ③ ECP Procedure ② Vascular Assessment • Venous Assessment Patient Education • Hematologic Considerations • HCT, PLTs ① Work up H & P Consent Patient Education Procedure WBCs isolated • Hydrate, hydrate, hydrate! from whole blood • Calcium-rich food Uvadex® mixed with WBCs • Stay warm • Stay away from UV light WBCs reinfused UVA light to the patient activates Uvadex® Treatment Trajectory • 2 days per week • CTCL Monthly x 6 months • Off-label at SCCA Regulatory Oversight – Acute GvHD • Weekly x 8 weeks → monthly – Chronic GvHD • Weekly x 4 weeks → bi-weekly x 3-6 mos. → monthly – Solid-organ Transplant Rejection • Weekly x 1 mo. → bi-weekly x 1 mo. → monthly for 4 mos. 6 6/6/2019 Regulatory Oversight Accreditation vs. Regulation FACT – Foundation for the Accreditation of Cellular Therapy • Voluntary quality assurance organization granting accreditation FDA – Food and Drug Administration. Accreditation Regulation • Federal laws that must be followed • Recognition • Law • Certification • 100% compliance • Improves performance expectation CAP – College of American Pathologists and safety REGS CAN • Quality control for laboratory aspects of apheresis GOOD TO SHUT US DOWN! HAVE! Resources • Apheresis Department page located on TogetherNet • Apheresis Unit 206.606.2120 • Apheresis Professional Practice Coordinator: Thank you! [email protected] • Apheresis Registered Nurse: [email protected] 7.