Exam 5 - Hematopoietic Growth Factors

Question 1

Erythropoietin; location, function:

Answer 1

Location: Produced by the kidney

Function: Stimulates proliferation/differentiation of RBC progenitors (take 5-7 days)

Question 2

Erythropoietin agents and t1/2:

Answer 2

Procrit; Epogen (recombinant), 4-13 hours

Darbepoetin alpha (Aranesp), 2-3 times longer than Erythropoietin

Epoetin beta (Mircea), pegylated erythropoietin so longer 1/2

Question 3

Erythropoietin agents AE:

Answer 3

hypertension and thromboembolism events, increased risk of tumor progression in cancer patients

Question 4

Granulocyte-Macrophage – Colony Stimulating Factor (GM-CSF):

Answer 4

Stimulates:
• early and late granulocytic progenitor cells
• erythroid and megakaryocyte progenitor cells

Stimulates mature PMN function

Acts with IL-2 to stimulate T-cell proliferation

Mobilizes peripheral stem cells (less effective than G-CSF)

Question 5

GM-CSF agent, indication, t1/2, AE:

Answer 5

Sargramostim (Leucine®) – recombinant

Indication: neutropenia

t1/2 : 2-7 hrs after i.v. or s.c. administration

AE: fever, arthralgia, myalgia, peripheral edema,
pleural/pericardial effusion

Question 6

Granulocyte–Colony Stimulating Factor (G-CSF):

Answer 6

Stimulates proliferation and differentiation of
granulocytic progenitor cells

Mobilizes hematopoietic cells; esp. peripheral stem cells

Question 7

G-CSF Agent, indication, t1/2:

Answer 7

Filgrastim (Neupogen)

t1/2: 4 hours

Pegfilgrastim (pegylated filgrastim): pegylated filgrastim w/ longer t1/2

Question 8

Effects of G-CSF on absolute PMNs (absolute neutrophil count):

Answer 8

Biphasic:

peak 1 = 5 to 7 days; recruitment of mature PMNs

peak 2 = 15-20 days; production of new, matured PMNs in bone marrow

Question 9

Megakaryocytic (platelet) Growth Factors:

Answer 9

Thrombopoietin and IL-11 are endogenous stimulators of megakaryocytes and platelet production

Low platelets = thrombocytopenia; increased risk of hemorrhage

Question 10

Oprelvekin (Neumega) (Recombinant IL-11) MOA:

Answer 10

Stimulates growth of megakaryocytic progenitors

Increases peripheral platelets

Question 11

Oprelvekin (Neumega) AE:

Answer 11

headache; dizziness

Cardiovascular events: anemia, atrial arrhythmia, dyspnea

Question 12

Romiplostim (“peptibody”) Indication:

Answer 12

Indication: idiopathic thrombocytopenia

Question 13

Romiplostim (“peptibody”) MOA:

Answer 13

• Stimulates megakaryocytes to produce platelets
• High affinity for human thrombopoietin receptor (Mpl)
• Dose-dependent  in platelets at 5d; peaks at 12-15 days