Growth Factor Medications

Erythropoiesis Stimulating Agent (ESA)

• Mechanism:

  • Regulates RBC production

  • Produced in liver in fetus, kidney is primary site in adults

  • Regulated by the HIF transcription factors

  • Functions by stabilizing CFU-e and promotes terminal differentiation of erythroid cells

• Ensure iron stores is adequate before using EPO

• Medications:

  • Erythropoietin/ Epoetin alfa (Epogen)

  • Darbopoietin alfa

  • Biosimilars

• Indications:

  • Chronic Kidney Disease

    • Start when Hb <10

    • Lowest dose necessary to reduce transfusion

    • Reduce/stop if Hb >11

    • Check iron stores (goal ferritin >100)

    • Escalate over 12 week period

  • Chemotherapy associated anemia (palliative intent)

    • Lowest dose necessary to reduce transfusion

    • Associated with increased risk for thrombosis

    • Stop if:

      • Hb increases by >1 in 2 week period

      • No longer requiring transfusions

      • Chemotherapy is done

    • Check iron stores (goal ferritin >100)

    • Escalate over 6-8 week period

  • Reduction of RBC transfusion in elective non-cardiac, non-vascular surgery

    • Given for 2 week course, starting 10 days prior to surgery

    • DVT ppx recommendeded

  • MDS (Discussed in separate post)

  • HIV

• Not indicated in:

  • Immediate correction of anemia

  • Chemotherapy associated anemia when anticipated outcome is cure

    • It shorten OS and time to progression in curable malignancies

  • Cardiac/vascular surgery

• Adverse events:

  • Allergic reactions

  • Hypertension

  • Seizures

  • Thrombosis

  • Decreased overall survival in cancer patients

  • Neutralizing antibodies can lead to pure red cell aplasia

• HIF prolyl-hydroxylase inhibitors:

  • Daprodustat, vadadustat, roxadustat

  • Increase transcription of HIF responsive genes → increase EPO levels

Granulocyte Colony Stimulating Factor (G-CSF)

• Indications:

  • Myelosuppressive chemotherapy with >20% neutropenic fever risk

    • Prophylactic if:

      • >20% risk of neutropenic fever

    • Therapeutic if:

      • Neutropenic fever + high-risk for infection-related complications + have not received prophylactic G-CSF (otherwise, routine use is not recommended)

        • High-risk features: age >65, sepsis, ANC <100, anticipated neutropenia >10 days, pneumonia, hospitalization at the time of fever, prior episodes of febrile neutropenia

      • If the patient is already receiving prophylactic G-CSF, it should be continued.

  • AML induction/consolidation

  • Hematopoietic Stem Cell Transplantation

    • Reduces engraftment time

  • Blood progenitor cell collection

    • Goal is 5 million CD34+ cells/kg recipient weight

  • Bone marrow failure syndromes

    • Theoretically not as beneficial in aplastic anemia (progenitor cells are not present)

• Administer 24-72 hours after completion of chemotherapy

• Adverse effects:

  • Allergic reactions

  • Bone pain (treat with NSAID and/or antihistamines)

  • ARDS

  • Splenic Rupture

  • Sickle Cell Crises

  • Sweet syndrome, cutaneous vasculitis

  • MDS/AML (0.4% absolute risk)

• Medications:

  • Filgrastim (Neupogen)

    • Recombinant protein made in E. coli

    • Half-life 3-4 hours

    • 5 mcg/kg (rounded to nearest vial size)

  • TBO-filgrastim

  • Biosimilars:

    • Filgrastim-sndz (Zarxio)

  • Pegfilgrastim (Neulasta)

    • Half-life of 15-80 hours

    • Only approved for:

      • Myelosuppressive chemotherapy with >20% neutropenic fever risk

      • Bone marrow failure syndromes

    • Single 6 mg subQ dose per cycle

    • Metabolized by neutrophils

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)

• Indications:

  • Induction chemotherapy in older patients (>55) with AML

  • Mobilization and following transplantation of auto-HSCT

  • Accelerate recovery following auto or allo-HSCT

• Contraindicated if blasts 10% or more

• Medications:

  • Sargramostim (Leukine)

  • Molgramostim

• Adverse effects:

  • Allergic reaction

  • Edema/ capillary leak syndrome

  • Pleural/pericardial effusion

  • Supraventricular tachycardia

• Clinical pearl: Used with sipuleucel-T in prostate cancer or TVEC in melanoma

Thrombomimetics (TPO)

• TPO made in liver and kidneys

• Binds to MPL receptor on platelets and marrow precursors

• Eltrombopag (Promacta): oral, non-peptide

  • Indicated for:

    • Chronic ITP

    • HCV-associated thrombocytopenia to allow use of interferon based therapy

    • Severe aplastic anemia when immune suppression fails

  • Dose: 50mg daily

    • 25mg daily for east asian or moderate/severe hepatic insufficiency

  • Adverse effects:

    • Nausea/vomiting, menorrhagia, arthralgia/myalgia, rare hepatic toxicity

• Avatrombopag (Doptelet): oral, non-peptide

  • 4x more potent than eltrombopag

  • Indicated for:

    • ITP and treatment of thrombocytopenia associated chronic liver disease who are scheduled to undergo a procedure (start 10-13 days before procedure)

  • Adverse effects:

    • Nausea, abdominal pain, fever, headache, arthralgia/myalgia, peripheral edema, thromboembolism

• Romiplostim (Nplate): peptide

  • Indicated for:

    • Chronic ITP with insufficient response to first line therapy

    • Severe thrombocytopenia with increased bleeding/risk of bleeding

    • Radiation injury

  • Starting dose at 1mcg/kg subq weekly

  • Adverse effects:

    • Bone marrow reticulin (myelofibrosis), thrombosis (not correlated with platelet count), increase in blasts (in patients with MDS)