Growth Factors Flashcards
Anemia is treated with
ESA
Neutropenia is treated with
CSF
Mucositis/stomatitis is treated with
Kerotinocyte GF
Two Lineages of Blood Stem Cells
Myeloid
Lymphoid
Myeloid makes
erythrocytes, platelets, monocytes, basophils, eosinophils and neutrophils
Lymphoid makes
Lymphocytes
Decreased oxygen delivery to kidney leads to
→ erythropoietin is generated by the kidneys due to sensing a low O2 level → increased oxygen delivery to tissues
Male Anemia
Less than 14
Female Anemia
Less than 12
Side effects of anemia
headache, dizziness, malabsorption
Moderate Anemia =
8-10
Severe Anemia =
6.5-7.9
What are the Cancer-Related Causes of Anemia
o Chemotherapy/radiation therapy o Anemia of chronic disease (leukemias, lymphomas, ovarian cancers) o Blood loss o Bone marrow infiltration o Nutritional deficiency o Hemolysis
Common cancers that cause Anemia
o Gynecological cancers, lymphoma/myeloma, and leukemi
Predisposing Factors for Anemia
Chemotherapy
Radiation
Combodities (renal, cancers)
Chemotherapeutic Agents that CAUSE anemia
Low grade: 5FU, taxels, CHOP, taxel + anthracycline
High: Toptecan, cisplatin, Ciplatin + etoposide, VIP
Benefits and Risk of RBC transfusions
o Graft-Versus-Host-Disease o Transfusion Related Acute Lung Injury o Allergy/anaphylaxis o Infections (HIV, HBV, HCV, HTLV, etc) o 1 Unit of RBC → 1 g/dL increase in 1 hour
ESA main purpose
Decrease the need for transfusions
ESA Drugs and Dosing
Epoetin alfa: 3 times a week
Barbepoeitin alfa: SC Qweekly
ESA AE
Fever, dehydration, vomiting, pneumonia, fatigue, THROMBOTIC EVENTS
ESA Caution
OVERALL INCREASE IN THROMBOVASCUALR EVENTS AND DECREASE SURVIVAL RATE
Why decreased overall survival rate with ESA
When you give EPO to cure anemia, you may be indirectly stimulating proliferation of cancer cells SO NEVER give EPO when you have a curable cancer because it increases tumor oxidation and growth
***WHEN TO USE ESA?
Chronic kidney disease, ESRD due to T2 DM
Non-myeloid and non-erythoid cancers
HIV-Induced
Patients undergoing hip or knee replacement surgery
Stem cell transplantation and immunosuppressed patients
Patients treated with chemotherapy and an Hgb level of
WHEN TO NOT USE ESA?
Curable cancers
Cancer-induced anemia
Hematological cancers (leukemia, lymphomas)
Neutropenia + Chemo
Most common dose-limiting toxicity
Between 7-14 days with recovery by day 21-28
Consequences of Neutropenia
Increased risk of infection, use of abx, and hospitalization
Compromises treatment efficacy
QofL impact
Prevention of Neutropenia
Dose reduction or delay
G-CSF or GM-CSF hematopoietic growth factors
What is G-CSF?
Glycoprotein + growth factor + cytokine
Presents on precursor cells in bone marrow where it initiates proliferation and differentiation into mature granulocytes to stimulate bone marrow cell release into circulation
Filgramstim MOA and Dose
• Regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation, differentiation and functional activation
Dose: daily for 4-14 days and last for 24 hours
Pegfilgramstim MOA and Dose
Pegylated form of filgramstim
Dose: one dose Q2weeks
Sacramostim MOA and Use
• Stimulates myelopoiesis generally and neutrophils and monocytes specifically
Used after BM transplan
Use of CSF
Post chemotherapy febrile neutropenia
When the risk of febrile neutropenia is 20% and no other equally effective regimen is available
Potent inducer of hematopoietic stem cell mobilization for stem cell transplant
Severe chronic neutropenia
Prevention of FN
Peripheral stem cell mobilzation
Accelerate recovery of neutrophils following stem cell transplantation
CSF Dosing
Always give 24 hours after starting chemotherapy
AE of CSF
Common: bone pain, elevated uric acid, arthralgia/myalgia
Serious: splenic rupture, sickle cell crsis, anaphylaxis, respiratory distress
Clinical Pearls of CSF
Begin at least 24 hrs after last dose of chemotherapy
No change in infection-related or overall mortality with treatment
Use for prevention of febrile neutropenia is better than treatment
Higher costs is an issue.
Define Mucositis
Inflammation of the mucosal surfaces through the body (esophagus, duodenum, colon, stomach, intestines, rectum)
Mucositis Mechanisms
Characterized by damage to the epithelium of the oropharyngeal cavity and GI tract
Release of cytokines and growth factors → Inflammation → Tissue damage → Ulceration of mucosa
Mucositis Symptoms
Pain
Difficulty eating/talking
Abdominal pain
Diarrhea
Complications
Impaired QofL
Decreased activity
Bacteremia/sepsis
Poor nutrition
Grade 1 Mucositis
Painless ulcers, erthema or mild soreness in the absence of lesions
Grade 2 Mucositis
Painful erythema, edema or ulcers but eating or swallowing possible
Grade 3 Mucositis
Painful erythema, edema, or ulcers requiring IV hydration
Grade 4 Mucositis
Severe ulceration or requiring parenteral or enteral nutritional support or prophylactic intubation
Phases Of Skin After giving Keratinocyte Growth Factor
o Phase 1: initiation: Reduce DNA damage; Increase levels of detoxifing enzymes to protect against ROS
o Phase 2: Signaling: Decrease levels of pro-inflammatory cytokines; Decrease apoptosis
o Phase 3: Amplification : Continuation of Phase 1 and 2
o Phase 4: Ulceration: As a result: reduced ulceration and pain
o Phase 5: healing
Keratinocyte Growth Factor Drug
Kepivance
Kepivance MOA
Induces cell proliferation, increases epithelial thickness and upregulates cytoprotective mechanisms
Kepivance Indications
Hematologic cancers, high dose chemo + total body irradiation, stem cell transplant
Kepivance AE
o Skin erythema
o Fatigue
o Tongue “feeling thick” or discoloration
o Taste disturbances
