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Myeloproliferative Disease Treatment & Management

  • Author: Haleem J Rasool, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Feb 26, 2016
 

Approach Considerations

Treatment of myeloproliferative neoplasms varies by disease subtype. For full discussion, see the following Medscape articles:

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Treatment of Chronic Myelogenous Leukemia

 

Imatinib mesylate (Gleevec), a bcr-abl –specific tyrosine kinase inhibitor (TKI), is approved for use in Philadelphia chromosome–positive chronic myelogenous leukemia (CML) in chronic phase. In one study at 18 months, the complete response rate was 76.2% and the major cytogenetic response rate was 87.1%. Imatinib is also indicated for CML in blast crisis, accelerated phase, or in chronic phase after interferon alfa therapy failure. This is the treatment of choice for most patients.[1]

Interferon alfa, usually administered as a subcutaneous daily injection in a dose of 5 million U, produces hematologic and molecular remissions in some patients with CML. In these patients, evidence shows that it prolongs survival. Several patients who achieved molecular remissions have survived for more than 10 years. Addition of low-dose cytosine arabinoside to interferon alfa has been reported to achieve higher remission rates. Patients with CML who are intolerant of interferon alfa therapy can be treated with hydroxyurea.

Dasatinib (Sprycel) is a TKI indicated for the treatment of adults patients with CML in chronic, accelerated, or myeloid or lymphoid blast phase who are resistant or intolerant to prior therapy including imatinib. Nilotinib (Tasigna) is a TKI indicated for the treatment of chronic phase and accelerated phase Philadelphia chromosome-positive CML in adult patients resistant to or intolerant to prior therapy including imatinib.

Hematopoietic stem cell transplantation can be considered in young patients with CML in chronic phase, if a human leukocyte antigen (HLA)-matched donor is available.

When the disease progresses to the blast phase (see the image below), it is treated as acute leukemia, though the outcome is usually grave.

Peripheral smear of a patient with chronic myeloge Peripheral smear of a patient with chronic myelogenous leukemia (CML) in blastic phase shows several blasts.

 

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Treatment of Polycythemia Vera

Treatment of polycythemia vera (PV) is palliative. Young (<40 y), asymptomatic patients with PV can be considered for therapeutic phlebotomies alone to maintain hematocrit level below 45%.

High-risk patients with systemic symptoms, history of thrombosis or bleeding, or high rate of phlebotomies or patients older than 69 years are best treated with myelosuppressive therapy in the form of hydroxyurea.[21] In December 2014, the US Food and Drug Administration (FDA) expanded the approval of the JAK1/JAK2 inhibitor, ruxolitinib (Jakafi) for the treatment of PV in patients who have an inadequate response to or cannot tolerate hydroxyureaAn alternative therapy.[22]

in older patients, radioactive phosphorus (32P) can be used for treatment of PV. However, this is unsuitable for younger patients because of the potential for causing secondary leukemia.

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Treatment of Essential Thrombocythemia

Treatment of essential thrombocythemia (ET) is meant to relieve symptoms and to prevent complications because no curative modality is available at present. The aim of treatment is to maintain the platelet count within the reference range. This usually can be achieved with hydroxyurea or anagrelide.

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Treatment of Primary Myelofibrosis

No curative treatment of primary myelofibrosis (MF) is available at the present time. Asymptomatic patients can be monitored clinically until symptoms develop. Treatment options for symptomatic MF include the following:

  • Anemia is treated with correction of reversible contributing factors, followed by erythropoiesis-stimulating agents, androgens, immunomodulating drugs, corticosteroids, and splenectomy; however, most patients eventually become transfusion dependent [23]
  • Hydroxyurea is useful to suppress the number of circulating cells
  • Patients with painful, massively enlarged spleens refractory to myelosuppressive therapy are occasionally treated with radiation therapy, but they may ultimately require splenectomy
  • Two case reports suggest that oral bisphosphonates may be beneficial in decreasing bone marrow fibrosis associated with this illness
  • Allogeneic hematopoietic stem cell transplantation is curative and may be an alternative for selected patients whose disease is refractory to conventional therapies [23]

In November 2011, the JAK1/JAK2 inhibitor, ruxolitinib (Jakafi), became the first US Food and Drug Administration (FDA)–approved drug for patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Approval was expedited in accordance with the US Orphan Drug Act and based on US and international data from the COMFORT-1 and COMFORT-2 trials. Results from the COMFORT-1 trial showed patients (n=309) who received ruxolitinib had a significant reduction in spleen volume (at least 35%) at 24 weeks when assessed by MRI or CT compared with placebo (41.9% vs 0.7%).[24]

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Consultations

See the list below:

  • Surgical consultation for permanent central venous access device placement may be required for patients in whom repeated blood draws, blood transfusions, and/or chemotherapy is anticipated.
  • A radiation oncologist may need to be involved in selected cases, when splenic radiation is considered appropriate.
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Diet and Activity

Massive splenomegaly is usually associated with epigastric and left upper quadrant discomfort and early satiety. Patients with these symptoms are encouraged to eat frequent, small meals rather than 3 large meals.

Individuals with myeloproliferative diseases are not encouraged to restrict their daily activities, but they are encouraged to refrain from physical activities that might expose them to abdominal trauma because massively enlarged spleens are likely to rupture, sometimes in response to minimal trauma.

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Contributor Information and Disclosures
Author

Haleem J Rasool, MD, FACP Chair, Department of Oncology, Mayo Clinic Health System, La Crosse, WI

Haleem J Rasool, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Koyamangalath Krishnan, MD, FRCP, FACP Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, Royal College of Physicians

Disclosure: Nothing to disclose.

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Peripheral smear of a patient with chronic myelogenous leukemia (CML) shows leukocytosis with extreme left shift and basophilia.
Peripheral smear of a patient with chronic myelogenous leukemia (CML) in blastic phase shows several blasts.
Peripheral smear of a patient with essential thrombocythemia (ET) shows markedly increased number of platelets. Some of the platelets are giant (arrow).
Peripheral smear of a patient with agnogenic myeloid metaplasia (myelofibrosis) shows leukoerythroblastosis. This photomicrograph also shows giant platelets.
Photomicrograph of a peripheral smear of a patient with agnogenic myeloid metaplasia (myelofibrosis) shows findings of leukoerythroblastosis, giant platelets, and few teardrop cells.
Table. Comparison of FAB and WHO Classifications of Chronic Myeloproliferative Diseases.
FAB WHO
Chronic myelogenous leukemia Chronic myelogenous leukemia, BCR/ABL1 positive
Polycythemia vera Polycythemia vera
Essential thrombocythemia Essential thrombocythemia
Agnogenic myeloid metaplasia/myelofibrosis Primary myelofibrosis
... Chronic neutrophilic leukemia, not otherwise specified
... Mastocytosis
... Myeloproliferative neoplasms, unclassifiable  
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