Myeloproliferative neoplasm medical therapy: Difference between revisions

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* History of thrombosis, ''or''
* History of thrombosis, ''or''
* Age > 60 with ''JAK2'' or ''MPL'' mutation present
* Age > 60 with ''JAK2'' or ''MPL'' mutation present
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* Aspirin twice daily ''plus'' hydroxyurea
* Aspirin twice daily ''plus'' hydroxyurea
''or''
''or''

Revision as of 17:33, 21 June 2018

Myeloproliferative Neoplasm Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2] Shyam Patel [3]

Overview

The mainstay of therapy for myeloproliferative neoplasm is chemotherapy, aspirin, and palliative care. Treatment is directed at reducing the excessive numbers of blood cells.[1]

Medical Therapy

Medical therapy for myeloproliferative neoplasm is based on the specific subtype of myeloproliferative neoplasm.

Polycythemia vera

Therapy Mechanism of Action Dosing Adverse Effects

Aspirin

Irreversibly inhibits cyclooxygenase-1 and -2 (COX-1 and COX-2)

81mg PO daily

Mucosal bleeding Gastrointestinal bleeding

Hydroxyurea

Inhibits ribonucleotide reductase

20mg/kg PO daily

Anemia, thrombocytopenia, ulcerations, secondary cancers

Ruxolitinib

Inhibits JAK2 (tyrosine kinase inhibitor)

10mg PO twice daily

Weight gain, zoster, non-melanoma skin cancers, cytopenias

Phlebotomy

Mechanically removes red blood cells from circulation

  • Induction: 450cc blood removal daily until hematocrit < 45%
  • Maintenance: One session every 2 months, with goal hematocrit < 45%

Iron deficiency anemia, fatigue, vasovagal episodes, pain at phlebotomy site

Essential thrombocythemia

Treatment of essential thrombocythemia is based on risk assessment and prognostication:

Prognostic Group Defining Features Treatment

Very low risk

  • No history of thrombosis
  • Age < 60
  • JAK2 or MPL wild-type
  • Observation, or
  • Aspirin once daily

Low risk

  • No history of thrombosis
  • Age < 60
  • JAK2 or MPL mutation present
  • Aspirin once daily, or
  • Aspirin twice daily

Intermediate risk

  • No history of thrombosis
  • Age > 60
  • JAK2 or MPL wild-type
  • Aspirin once daily plus hydroxyurea

High risk

  • History of thrombosis, or
  • Age > 60 with JAK2 or MPL mutation present
  • Aspirin twice daily plus hydroxyurea

or

  • Hydroxyurea, plus systemic anticoagulation


Therapy Mechanism of Action Dosing Adverse Effects

Anagrelide

  • Inhibits phosphodiesterase 3 (PDE-3)
  • Inhibits release of arachidonic acid from phospholipase A2
  • Disrupts maturation of megakaryocytes

0.5mg PO every 6 hours or 1mg every 12 hours

Headache, palpitations, diarrhea, edema, nausea

Hydroxyurea

Inhibits ribonucleotide reductase

20mg/kg PO daily

Anemia, thrombocytopenia, ulcerations, secondary cancers

Aspirin

Irreversibly inhibits cyclooxygenase-1 and -2 (COX-1 and COX-2)

81mg PO twice daily

Mucosal bleeding Gastrointestinal bleeding

Ruxolitinib

Inhibits JAK2 (tyrosine kinase inhibitor)

10mg PO twice daily

Weight gain, zoster, non-melanoma skin cancers, cytopenias

Plateletpheresis

Mechanically removes platelets from circulation

Daily until platelet count returns to normal range

Hypotension, thrombocytopenia

Pegylated interferon alpha 2a

Immunomodulatory agent; anti-angiogenic agent

45mcg/week

Hypotension, infusion reaction

Primary myelofibrosis

Therapy Mechanism of Action Dosing Adverse Effects

Hydroxyurea

Inhibits ribonucleotide reductase

20mg/kg PO daily

Anemia, thrombocytopenia, ulcerations, secondary cancers

Ruxolitinib

Inhibits JAK2 (tyrosine kinase inhibitor)

10mg PO twice daily

Weight gain, zoster, non-melanoma skin cancers, cytopenias

Radiation therapy

Unknown mechanism

0.5 Gy to spleen 5 days weekly

Fatigue, secondary cancers, nausea, cytopenias

Chronic myeloid leukemia

Therapy Mechanism of Action Dosing Adverse Effects

Imatinib

Inhibits BCR-ABL tyrosine kinase

400mg PO daily

Edema, periorbital swelling, nausea, anasarca

Dasatinib

Inhibits BCR-ABL tyrosine kinase

100mg PO daily

Pleural effusions, edema, periorbital swelling, facial edema

Nilotinib

Inhibits BCR-ABL tyrosine kinase

400mg PO twice daily

Occlusive arterial disease, peripheral vascular disease, cytopenias, nausea

Bosutinib

Inhibits BCR-ABL tyrosine kinase

400mg PO daily

Edema, chest pain, fatigue, diarrhea

Ponatinib

Inhibits BCR-ABL tyrosine kinase

45mg PO daily

Hypertension, arterial ischemia, fatigue, constipation

Omacetaxine

Inhibits protein synthesis

  • Induction: 1.25mg/m2 subQ twice daily for 14 days of a 28-day cycle
  • Maintenance: 1.25mg/m2 subQ twice daily for 7 days of a 28-day cycle

Peripheral edema, fatigue, nausea, thrombocytopenia

Chronic neutrophilic leukemia

Therapy Mechanism of Action Dosing Adverse Effects

Hydroxyurea

Inhibits ribonucleotide reductase

20mg/kg PO daily

Anemia, thrombocytopenia, ulcerations, secondary cancers

Pegylated interferon alpha 2a

Immunomodulatory agent; anti-angiogenic agent

45mcg/week

Hypotension, infusion reaction

References

  1. National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/leukemia/hp/cml-treatment-pdq#section/_19

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