Objectives. The Nurse s Role? Why do we need to know this? 2/18/2015

Transcription

1 Objectives Juanita Madison, RN, MN, AOCN CHI Franciscan Health Describe the hematopoietic system How blood cells are developed Role & function of blood cells Growth factors that stimulate blood cell development Identify differences between innate and acquired immunity. Review areas of research for innovative therapies. Why do we need to know this? The Nurse s Role? Provides an understanding of signs & symptoms/side effects that occur due to disruptions in: Production of blood cells Immune system Provides an understanding of treatments aimed at: Boosting production of blood cell lines Utilizing body s own mechanisms to fight cancer and/or mitigate side effects What is the patient at risk for? When is the patient at risk? What are the primary nursing intervention(s)? What education should be provided? 1

2 All blood cells have two things in common: Originate from a common progenitor cell Develop through a process called hematopoiesis Hematopoiesis Process of blood cell formation Red blood cells Platelets White blood cells Greek origin Haima : blood Poiesis : to make Bone Marrow Environment Vessels Marrow Sinuses Marrow Stroma Supportive structure Regulatory proteins Cells 8 2

3 Pluripotent Stem Cell Hematopoietic cell Source of all cells uncommitted Progenitor Self renewing Location Marrow Peripheral Blood (CD34+) Migratory properties 3

4 Commitment Myeloid Lineage Erythrocyte Platelet Granulocyte Neutrophil Basophil/mast cell Eosinophil Monocyte / macrophage Dendritic cell Antigen Presenting Cell Lymphoid Lineage B lymphocyte T lymphocyte Dendritic Cell Follicular Presenting Cell Natural Killer Cell (NK) Cytokines Proteins released by cells Messengers of the immune system Released by cells throughout the body Provide communication between cells of immune system Mechanism of action: Bind to surface receptors of target cells Act as regulators of cell growth or mediators of defense functions Cytokines in cancer treatment Colony Stimulating Factors (Hematopoietic Growth Factors) Erythropoietin (EPO) Granulocyte-colony stimulating factory (G-CSF) Interferons Interleukins Erythrocytes Erythropoiesis Feedback Mechanism Functions: O 2 /C0 2 Transport and exchange Acid Base Balance Normal: M: million cells/mm 3 Erythropoietin (EPO) Cytokine (protein signaling molecule) for erythrocyte precursors Produced by the kidneys F: million cells/mm 3 Production: 2.5 billion/kg/day Life span: days 4

5 Anemia A term that indicates a low red cell count and a below normal hemoglobin or hematocrit level. Hemoglobin (g/dl) Grade Severity of Anemia Within normal limits 0 Normal 10 - normal 1 Mild 8 - <10 2 Moderate < 8 3 Severe < Life threatening Caused by Decreased production of RBC Increased destruction of RBC Blood loss Anemia Risk Factors Cancer Radiation Myelosuppressive chemotherapy Platinum containing regimens Low Hgb prior to start of chemo Incidence 50% Higher incidence with subsequent treatments Adapted from the Common Toxicity Criteria for Adverse Events, Version 4.03 June 14, Available at: Anemia - Treatment Red Blood Cell transfusion Iron, folate and B 12 supplementation Erythropoietin stimulating agents Erythropoietic-Stimulating Agents (ESA s) Mechanism of action: Stimulates erythropoiesis via same mechanism as endogenous erythropoietin (EPO) Indications: Chemotherapy-induced anemia Anemia due to chronic kidney disease in patients on dialysis and not on dialysis Agents Epoetin alfa (Procrit, Epogen ) ) Darbepoetin (Aranesp ) Amgen, Inc., 2012; Janssen Products, LP,

6 Erythropoietic-Stimulating Agents (ESA s) Route(s) of administration: Subcutaneous, IV Side effects: Risk of tumor progression or shortened overall survival Hypertension; Risk of death, stroke, thrombosis, and serious cardiovascular events is increased if hemoglobin >11g/dl when administered Erythropoietic-Stimulating Agents (ESA s) Dosing Epoetin Alfa (Procrit, Epogen ): Darbepoetin (Aranesp ) FDA Approved Dosing 40,000 U weekly Or 150 U/kg three times a week 2.25 mcg/kg weekly Or 500 mcg Q 3 weeks NCCN Alternate Dosing Regimens 80,000 U Q 2 weeks Or 120,000 U Q 3 week 100 mcg fixed Q week Or 200 mcg Q 2 weeks OR 300 mcg Q 3 weeks Amgen, Inc., 2012; Janssen Products, LP, Amgen, Inc.,2012; Janssen Products, LP, 2013; NCCN, Erythropoietic-Stimulating Agents: Nursing Implications Not indicated for cancer patients when cure is anticipated outcome of treatment Ensure adequate iron stores in patients prior to and during use Do not shake vials or syringes containing drug REM (Risk Evaluation and Mitigation Strategy) Prescriber and hospital must enroll in the ESA APPRISE Oncology Program Amgen, Inc.; Janssen Products, LP., What is a REMS? Risk Evaluation and Mitigation Strategy (REMS) A program established under the Food and Drug Administration Amendments Act (FDAAA) of 2007 Grants the FDA the authority to require a drug manufacturer to develop and implement a REMS if the FDA determines that a REMS is necessary to ensure that the benefits of a drug outweigh the risks. Aranesp and Procrit REMS key components: Prescriber/Hospital training (online) Enroll in ESA APPRISE Oncology Program Counsel each patient re: risks prior to each course of therapy & document risk: benefit discussion (on specific forms) Risks for patients with cancer: increased risk of death and/or increased risk of tumor progression or recurrence US Food and Drug Administration,

7 Thrombocytes (Platelets) Function: Hemostasis Normal: 150, ,000 cells/mm 3 Production: 2.5 billion/kg/day Life span: 7-10 days Thrombocytopenia Decreased number of circulating platelets Platelet Count (mm 3 ) Grade Severity of Anemia Within normal limits 0 Normal 75,000 - normal 1 Mild 50,000 - <75,000 2 Moderate 25,000 - < 50,000 3 Severe < 25,000 4 Life threatening Adapted from the Common Toxicity Criteria for Adverse Events, Version 4.03 June 14, Available at: Thrombocytopenia Signs/Symptoms of Bleeding Petechiae Bruising Overt/occult Oral Nasopharynx GI Urinary tract Treatment of Thrombocytopenia Platelet Transfusions Interleukin-11 (Neumega ) Oprelvekin (IL-11, Neumega ) Route of administration: Subcutaneous Special dosing considerations: Daily subcutaneous administration starting at 6-24 hours postchemotherapy administration and continuing until platelet count >50,000 Discontinue 2 days before next chemotherapy dose Common indications: Prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in adult patients with nonmyeloid malignancies who are at high risk of severe thrombocytopenia Pfizer, Inc.,

8 Oprelvekin (IL-11, Neumega ) Side Effects: Peripheral edema, pulmonary edema, dyspnea, tachycardia, conjunctival injection, palpitations, atrial arrhythmias, pleural effusions, fever, headache, nausea, vomiting, insomnia, rhinitis Nursing Considerations: Use with caution in patients with preexisting CHF or other conditions that may be exacerbated by fluid retention Sound-alike/look-alike warning: do not confuse with Neulasta Leukocyte Function Cell Type Function When Absent Neutrophil Phagocytosis Bacterial Infection Eosinophil Basophil Allergic reaction Defense against parasites Allergic & inflammatory reactions Parasitic Infections Inadequate inflammatory response Monocyte Phagocytosis Fungal infection Lymphocyte Immunity Viral infections Opportunistic infections Cancer Pfizer, Inc., Neutrophils Phagocytic cells Early responder to infection When low: susceptible to bacterial infection Capacity for infection fighting/defense Advantage Limited stimuli provoke a response Early response in large numbers Effective killing bacteria, digest debris (healing) Disadvantage Unable to recognize many injurious agents Cannot modify response (i.e. doesn t learn ) Neutrophils Normal Values 60%-80% of total WBC count ( cells/mm 3 ) Life span: 4-10 hours (circulating neutrophils) Production: 1 billion/kg/day What types of patients might be susceptible to infections due to neutrophil counts 8

9 Neutrophil Functional Neutrophils Polymorphonuclear cell (polys) or segmented neutrophil Banded neutrophil (Band) - less mature Absolute Neutrophil Count (ANC) Represents number of functional neutrophils Number of circulating Polys + Bands Used as an indicator to determine: Risk of infection Ability to continue therapy Assessing Neutrophils: The Absolute Neutrophil Count (ANC) ANC = Total WBC X % of neutrophils (segs + bands) Example: WBC = 2,500/mm 3 Segmented neutrophils = 35% Band neutrophils = 10% ANC = 2,500 X ( ) = ANC = 2,500 X.45 = 1,125/mm 3 Neutropenia Decreased number of circulating neutrophils ANC predicts risk of infection Neutrophil Count (mm 3 ) Grade Severity of Anemia Within normal limits 0 No Risk 1,500 - normal 1 No significant risk 1,000 - <1,500 2 Minimal risk < 1,000 3 Moderate risk < Severe risk Adapted from the Common Toxicity Criteria for Adverse Events, Version 4.03 June 14, Available at: 9

10 Consequences of Neutropenia Increased hospital admission Increased risk for infection Higher costs of treatment Delay in treatment Increased risk of unsuccessful treatment Granulocyte-Colony-Stimulating Factors (G-CSF) Mechanisms of action: Regulates production of neutrophils in bone marrow Side effects of drug class: Most common: Bone pain Allergic reactions, splenic rupture, ARDS, may induce sicklecell crisis in patients with sickle-cell disease Nursing considerations for drug class: Store in refrigerator, do not freeze Do not shake vials or syringes containing drug Bone pain may require analgesics such as acetaminophen or NSAIDS Amgen, Inc., 2014; Teva Oncology, Filgrastim (Neupogen ) tbo-filgrastim (Granix ) Route of administration: Subcutaneous (filgrastim & tbo-filgrastim) IV (filgrastim only) Nursing considerations First dose should be administered at least 24 hours after chemotherapy Avoid use 24 hours before chemotherapy is administered Amgen, Inc., 2014; Teva Oncology, Pegfilgrastim (Neulasta ) Route of administration Subcutaneous Nursing Considerations Longer half life 1 dose equivalent to 11 daily injections of G-CSF Self regulating Administer as 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 Amgen, Inc.,

11 More on neutropenia on day 2 during the Myelosuppression and Fatigue content More on leukemia's (too many WBC) during day 3 lectures. The Immune System How does it learn to adapt? How can we utilize it to help combat cancer? The Immune System The immune system is an integrated system that has four primary functions: Protection Surveillance Homeostasis Regulation Immune System: Innate versus Adaptive Immunity Innate Features Primary defense Non-specific No memory Responses Inflammatory response: Phagocytic cells respond to bacteria, fungus, and parasites Components Skin and mucous membranes Phagocytic cells Complement system Adaptive Secondary defense Specific Has memory Lymphocytes respond: T-cells: surveillance, rejection, virus B-cells: antibody, virus, bacteria Lymphoid system Lymphocytes Antibodies 11

12 Structures of the Immune system Skin & Mucous Membranes Mechanical barrier Intact Shedding epidermis and mucosal cells Chemical barrier ph of skin Secretions of antimicrobial chemicals (in saliva, mucus, tears and sweat) Lymphoid system Cellular Components of the Immune System Innate / Natural immunity Natural Killer cells (CD56 + ) Lymphocytes Lack markers found on B and T cells Kill tumor cells and virally infected cells without previous exposure Non-specific: can respond to a variety of antigens Part of the innate immune system Antigen Presenting Cells (APC s) -Help lymphocytes recognize antigens on foreign cells (including cancer cells) -Include: monocytes, macrophages, dendritic cells 12

13 Immune System: Monocytes Monocyte patrol the bloodstream sample surroundings Present antigen of ingested material Secrete cytokines If absent: fungal infections Immune system: Macrophage Greek: big eaters, from makros "large" + phagein "eat Found in tissue Versatile Present antigens Scavenge Dendritic Cell Also called Antigen Presenting Cell (APC) Recognized as major cells in the immune system 1973 Phagocytic cells Present antigen of ingested material Single cell can activate 100-3,000 T cells Adaptive Immunity Humoral immunity Utilizes B lymphocytes, memory B cells and plasma cells End result is production of immunoglobulin's Cell-mediated immunity Mediated by T-cells and cytokines No antibodies involved but uses cytotoxic T-cells (CD8 + ) and Helper T-cells (CD4 + ) 13

14 Lymphocytes Specific/Adaptive immunity Differentiate between self and non-self (self tolerance) T Lymphocytes Cell mediated immunity B Lymphocytes Humoral immunity 20% of total WBC count B (Bone Marrow) Lymphocytes Humoral/Specific Immunity Plasma cell precursors These respond to antigens and produce immunoglobulins Immunoglobulins (A.K.A. antibodies) are protein products of plasma cells 5 major immunoglobulins Matures in Bone marrow Normal: cells/mm 3 T (Thymus) Lymphocyte Cellular/Specific Immunity Cytotoxic T cells (CD8 + ) Kill foreign cells and cells that have viral infections T-Helper cells (CD4 + ) Stimulate B cells, call in phagocytes and activate other T cells T-regulatory cells/suppressor T Interfere with immune response, work to prevent development of autoimmunity Memory T-cells Recognize specific antigens Matures in Thymus Activated when APC presents antigen Normal: cells/mm 3 Immune System Role in Cancer Prevention/Control Detect and destroy cancer cells through recognition of non-self Cancer cells have non-self antigens on surface tumor associated antigens Immunocompromised have > incidence of cancer Theory of how malignant cells elude immune system Internalize cell-surface Ag Glycoproteins cover-up antigenic markers Tumor cells closely resemble normal cells 14

15 Fast Facts Immunosuppresion associated with increased risk of malignancy Patients who had a strong immune response that infiltrated some specific types of tumors with T-cells or NK cells have a more favorable prognosis Using the Immune System to Treat Cancer Monoclonal antibodies Used to bind to specific antigen on a cell surface Cytokines Interferons Interferon alfa-2b (Intron A) Interleukins Aldesleukin (IL-2, Proleukin ) Granulocyte colony-stimulating factors (G-CSF) Filgrastim (Neupogen ) Tbo-filgrastim (Granix ) Pegfilgrastim (Neulasta ) Erythropoiesis-stimulation factor: EPO Epoetin alfa (Procrit, Epogen ) Darbepoetin (Aranesp ) Vaccines Use dendritic cells (or antigen presenting cells) Culture dendritic cells CD34+ bone marrow precursor cells CD14+ monocytes Load with tumor lysates or antigens from the patient Re-infuse Provoke an immune response against tumor Novel Therapies Metastatic prostate cancer Provenge Autologous cellular immunotherapy Malignant Melanoma: Ipilimumab & Tremelimumab: block a specific molecule and allows increased immune system activity against tumor antigens 15

16 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. Colony Stimulating factors act on the stem cells to specifically mediate which of the following steps in Hematopoiesis? A. Cellular Proliferation B. Cellular differentiation C. Stem cell maturation D. All of the above Resources Oncology Educational Services (OES) National Comprehensive Cancer Network Capo, G. & Waltzman, R. (2004). Managing Hematologic Toxicities. Supportive Oncology, 2(1), NIH & NCI (2003). Biological Therapy: Treatments that use your immune system to fight cancer. NIH and NCI (2006). Understanding Cancer: The Immune System. /immunesystem Resources (continued) Steenhuysen, J. (2009) Fat cells in bone marrow impair transplant healing Reuters, RJ , retrieved June 10, The Dana Sourcebook of Immunology. Dana Press. on.aspx?id=4382. Retrieved August 10,