Myeloproliferative neoplasm medical therapy

Myeloproliferative Neoplasm Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating myeloproliferative neoplasm from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications, and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X-ray
Echocardiography and Ultrasound
CT scan
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Myeloproliferative neoplasm medical therapy On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Myeloproliferative neoplasm medical therapy All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Myeloproliferative neoplasm medical therapy
on Myeloproliferative neoplasm medical therapy
Myeloproliferative neoplasm medical therapy in the news
Blogs on Myeloproliferative neoplasm medical therapy
Directions to Hospitals Treating Myeloproliferative neoplasm
Risk calculators and risk factors for Myeloproliferative neoplasm medical therapy

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

Chronic eosinophilic leukemia

Therapy	Mechanism of Action	Dosing	Adverse Effects
Imatinib	Inhibits PDGFR tyrosine kinases	100mg PO daily	Edema, periorbital swelling, nausea, anasarca
style="padding: 5px 5px; background: #DCDCDC;font-weight: bold"	Corticosteroids	Immunosuppressive agent; inhibits IL-2 and COX2	Variable; typical dose is 1mg/kg/day	Infections, cataract, glaucoma, bone loss, muscular atrophy

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	Tyrosine kinase inhibitor that inhibits wild-type c-kit and mutant c-kit D816V	10mg PO twice daily	Nausea, hypocalcemia, mucositis, headache, epistaxis, hypernatremia