Chapter 56 Hematopoietic Agents 1

Hematopoietic Agents Process by which blood cells and platelets are produced Types Hematopoietic growth factor Erythropoietic (RBCs) Leukopoietic (WBCs) Thrombopoietic growth factor Oprelvekin (platelets) 2

Erythropoietic Growth Factors Also known as ESAs (erythropoiesis-stimulating agents) Adverse effects Increased risk of deep vein thrombosis (DVT) when used before elective surgery For patients with cancer Can shorten time to tumor progression Reduce overall survival 3

Epoetin Alfa (Erythropoietin) Brand names: Epogen, Procrit Hematopoietic growth factor Significant effects outside hematopoietic system Recombinant DNA technology Uses Anemia associated with chronic renal failure Chemotherapy-induced anemia For HIV-infected patients taking zidovudine Anemia in patients facing surgery 4

Epoetin Alfa (Erythropoietin) Adverse effects Hypertension Autoimmune pure red-cell aplasia Very rare Cardiovascular events Cardiac arrest Heart failure Thrombotic events (stroke and MI) 5

Epoetin Alfa (Erythropoietin) Warnings Excessive dosage Cancer patients Renal failure patients Preoperative patients Risk evaluation and mitigation strategy 6

Epoetin Alfa (Erythropoietin) Dosage To minimize risks Use minimum needed to gradually raise hemoglobin content to eliminate the need for RBC transfusions Hemoglobin level should not exceed 12 g/dL Monitoring Monitor hemoglobin level twice weekly 7

Longer-Acting Erythropoietins Darbepoetin alfa (long-acting) Similar risks and needs for monitoring as epoetin alfa Patients with hypertension may need increased hypertension medications Methoxy polyethylene glycol: epoetin beta (very long-acting) Not marketed in the United States (ongoing patent dispute) 8

Filgrastim (Neupogen) Granulocyte colony-stimulating factor Leukopoietic growth factor Recombinant DNA technology Reduces the incidence of severe neutropenia Produces dose-dependent increase in circulating neutrophils Reduces the incidence of infection, need for hospitalization, and need for intravenous antibiotics 9

Filgrastim (Neupogen) Uses Cancer Severe chronic neutropenia Adverse effects Bone pain Leukocytosis 10

Pegfilgrastim (Granulocyte Colony-Stimulating Factor) Long-acting Derivative of filgrastim (Neupogen) Stimulates myeloid cells to increase production of neutrophils Adverse effects Similar to filgrastim May require opioids for pain relief 11

Sargramostim (Granulocyte-Macrophage Colony-Stimulating Factor) Brand name: Leukine Hematopoietic growth factor Recombinant DNA technology Uses Adjunct to autologous bone marrow transplantation Treatment of failed bone marrow transplants Patients with acute myelogenous leukemia (AML) Adverse effects Leukocytosis Thrombocytosis 12

Oprelvekin (Interleukin-11) Brand name: Neumega Thrombopoietic growth factor Recombinant DNA technology Uses Used with myelosuppressive chemotherapy to minimize thrombocytopenia and to decrease the need for platelet transfusions Adverse effects Fluid retention Cardiac dysrhythmias Effects on the eye Sudden death 13

Drugs Related to Hematopoietic Growth Factors Romiplostim Eltrombopag Plerixafor

CAUTION Epoetin alfa, filgrastim, sargramostim, and oprelvekin stimulate proliferation of bone marrow cells. USE WITH GREAT CAUTION, if at all, for patients with cancers of bone marrow origin. 15