Hematopoiesis, Growth Factors, and Immunology Kelley Blake MSN, RN, AOCNS, OCN UW Medicine/Valley Medical Center

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1 Objectives Hematopoiesis, Growth Factors, and Immunology Kelley Blake MSN, RN, AOCNS, OCN UW Medicine/Valley Medical Center Describe the hematopoietic system How blood cells are developed Role & function of blood cells Growth factors that stimulate blood cell development Review basic function and cellular components of the immune system Identify how the immune system is used to treat cancer Hematopoiesis Process of blood cell formation Red Blood Cells Platelets White Blood Cells Greek origin Haima : blood Poieses : to make Adult Hematopoiesis Occurs in the bone Sternum Iliac Crest Skull Vertebrae Ribs Proximal epiphysis of long bones Only occurs in Red marrow Yellow marrow Fatty cells that eventually crowds out red marrow 1

2 Cytokines Mediators of the immune system Molecules that: Enhance communication Induce growth and differentiation of lymphocytes and other cells Messengers Released by cells Bind to surface receptors of target cells Provide communication between cells Interferons (IFNs) Interleukins (ILs) Hematopoietic growth factors Erythropoietin (EPO) Granulocyte colonystimulating factor (G- CSF) Granulocyte macrophage colonystimulating factor (GM-CSF) Tumor necrosis factor (TN) Chemokines Examples of Cytokines Schmidt, K. & Warren, T. (2016). "Immunology", in Itano, et al (Eds). Core Curriculum for Oncology Nursing, 5th Ed. ONS, Pittsburgh, PA pp Question When you think of blood cells, what is the first thing that comes to mind? 2

3 O2/C02 Transport and exchange Acid Base Balance Normal: M: million cells/mm3 F: million cells/mm3 Production 2.5 billion/kg/day Stem cell RBC 3 5 days Life span of days Hypoxic conditions trigger erythropoiesis Erythrocytes Erythropoietic-Stimulating Agents (ESA s) Mechanism of action Same as endogenous erythropoietin Indications Chemotherapy-induced anemia Anemia due to chronic kidney disease Agents Epoetin alfa (Procrit, Epogen ) Darbepoetin (Aranesp ) Thrombocytes Hemostasis (blood clotting) Normal: 150, ,000 cells/mm3 Production: 2.5 billion/kg/day Life span: 7-10 days Thrombopoietic Growth Factor Oprelvekin (IL-11, Neumega) Indications Prevent severe thrombocytopenia Reduce platelet transfusions Patients with non-myeloid malignancies Receiving chemotherapy High risk severe thrombocytopenia Route of administration Subcutaneous Nursing considerations Begin 6-24 hours after therapy completion Discontinue when platelets >50,000 & 2 days before next chemotherapy cycle 3

4 Leukocytes Formed in bone marrow and lymph tissue Myeloid Lymphoid Mobile Part of body s protective system Leukocyte Cell Types Leukocyte Function Neutrophils Cell Type Function Complication when absent Neutrophil Phagocytosis Bacterial infection Eosinophil Basophil Allergic reaction, defense parasite Allergic/inflammatory reaction Parasitic infections Inadequate inflammatory response Monocyte Phagocytosis Fungal infection Lymphocyte Long term Immunity Viral and opportunistic infections, cancer Normal Values 60%-80% of total WBC count ( cells/mm3) Majority stored in marrow Circulate - 1/2 life 4-10 hrs Produce 1 billion/kg/day Phagocytic cells Early responder to infection Susceptible to bacterial infection Segs Bands 4

5 Granulocyte Colony-Stimulating Factors (G-CSFs): Cytokines Filgrastim (Neupogen ) Tbo-filgrastim (Granix ) Filgrastim-sndz (Zaroxio ) Route of administration Subcutaneous (filgrastim & tbo-filgrastim) IV (filgrastim only) Nursing considerations First dose should be administered at least 24 hours after chemotherapy Granulocyte Colony-Stimulating Factors (G-CSFs): Cytokines Pegfilgrastim (Neulasta ) Route of administration Subcutaneous Nursing considerations Longer half life Administer as a single 6 mg injection once per chemotherapy cycle Do not administer in the period beginning 14 days before or until 24 hours after administration of myelosuppressive chemotherapy Granulocyte Colony-Stimulating Factors (G-CSFs): Cytokines Onpro on-body injector (Neulasta ) Antigen Presenting Cells (APCs) Help lymphocytes recognize antigens on foreign cells Including cancer cells Include: Monocytes Macrophages Dendritic cells 5

6 Respond to inflammation & infection T- & B-cell activation In circulation Life span 8-72 hrs Precursors for macrophages & dendritic cells Will further differentiate into these cell types as the need arises Monocytes Greek: big eaters Makros large + phagein eat Seize and engulf foreign materials Found in tissue Life span up to 3 mo T- & B-cell activation Macrophages Dendritic Cells (DCs) Lymphocytes Tissue secondary lymphoid organs T- & B-cell activation Stimulates both antiviral & antitumor immune responses Specific/Adaptive immunity Differentiate Self and non-self T Lymphocytes Cell mediated immunity B Lymphocytes Humoral immunity Natural Killer cells (NK) 20% of total WBC count with viral infection 6

7 B Lymphocytes T Lymphocytes Mature in bone marrow Function Multiply on recognition of a specific antigen Further differentiate into plasma cells Produce one of 5 types of immunoglobulins (IgG, IgA, IgM, IgE, IgD) Produced in the bone marrow Develops in thymus gland Immune surveillance Activated by APCs TH: maintain cytotoxic T cell (CD4) TC: kill foreign cells (CD8) Treg/TS: modulate severity of inflammation TM: recall responses Cytotoxic T: immune checkpoint (CTLA-4) Null Cells/Natural Killer Cells Separate lineage of lymphoid cells Contain substances that create a hole in membrane of cell Perforin Serine proteases Enzymes Activity increased with cytokines Interleukin-2 (IL-2), IL-12 Interferon gamma Function: Identification and destruction Virus-infected cells Certain tumor cells Question Why is it important to understand hematopoiesis and the function of blood cells in cancer treatment? 7

8 Immune System Innate vs Adaptive Immunity Protection Infection Surveillance Recognize and destroy foreign substances Homeostasis Destruction Abnormal Malignant Worn Damaged Mutated cells Regulation Enhance/suppress immune response Features Function Innate Primary defense Non-specific No memory Inflammatory response Phagocytic cells: bacteria, fungus, parasites Adaptive Secondary defense Specific Memory Lymphocytes T cell-surveillance, rejection, virus B cell-antibody, virus, bacteria Chemotherapy and Biotherapy Guidelines: and recommendations for practice (2014). ONS. Organs of Lymphoid System Immunosurveillance 1⁰ 2⁰ 2⁰ 2⁰ Immune system identifying and controlling tumor cells (Vesely & Schrieber, 2013) A theory that the immune system patrols the body not only to recognize and destroy invading pathogens, but also host cells that become cancerous Immune escape Loss of recognition by cells within the immune system, which leads to tumor escape and cell proliferation (Devita, et al, 2011) 1⁰ 8

9 Question If our immune system destroys tumor cells, then why does cancer exist? Mechanisms of Cancer Development Defective T cells and dendritic cells Immunosuppression Immunosuppressive cytokines Angiogenesis Forms blood vessels for food/energy Metastasis Invades other tissues/spread Immunoevasion Evade checkpoints/cell signals Mitosis continues Avoids apoptosis Evade the immune system Avoids destruction Syal, K & Banerjee, D (2012). Theories of immunosurveillance/immunoevasion: An attempt to explain persistence of cancer, IOSR Journal of Pharmacy, 2(1):

10 Immunotherapy Treatment that restores or enhances the immune system s natural ability to fight diseases, including cancer Described as a way to fire up the immune system s response to cancer (Ledford, 2015, p.24) Question How does immunotherapy work? Immunotherapy Immunotherapy works by Stopping or slowing the growth of cancer cells Stopping cancer from spreading to other parts of the body Helping the immune system recognize cancer cells and increase its effectiveness at eliminating cancer cells Types of Immunotherapy: Passive Enhances preexisting immune response Requires repeated administration to be effective Short-term response Example Monoclonal antibodies 10

11 Types of Immunotherapy: Active Engages the immune system Capitalizes on immune system s ability to remember foreign invaders More durable response Example Cancer vaccines Types of Immunotherapy: Specific Capitalizes on tumor markers or tumorassociated antigens to specifically target and kill cancer cells Example Monoclonal antibodies Types of Immunotherapy: Non-specific Stimulates a large immune response Given adjuvant to other anticancer treatments Examples Cytokines Interleukins Checkpoint inhibitors Question Which of the following best describes what cytokines do? a. They bind to surface receptors of target cells and act as regulators of cell growth or as mediators of defense functions b. They are capable of non-specific tumor cell killing c. They are sedentary cells located in the spleen d. They facilitate the attachment of a natural killer cell and other cytotoxic cells 11

12 Kelley Blake MSN, RN, AOCNS, OCN UW Medicine/Valley Medical Center 12