Myeloproliferative neoplasm medical therapy

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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.

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	Therapy
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

Systemic mastocytosis

Therapy	Mechanism of Action	Dosing	Adverse Effects
Imatinib	Tyrosine kinase inhibitor that inhibits wild-type c-kit; not effective for c-kit D816V mutation	400mg PO daily	Edema, periorbital swelling, nausea, anasarca
Midostaurin	Immunomodulatory agent; anti-angiogenic agent	Tyrosine kinase inhibitor that inhibits wild-type c-kit and mutant c-kit D816V	10mg PO twice daily	Nausea, hypocalcemia, mucositis, headache, epistaxis, hypernatremia