MPNs – Causes, Symptoms, Diagnosis, Treatment

MPNs (Myeloproliferative neoplasms) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. Myelo refers to the bone marrow, proliferative describes the rapid growth of blood cells and neoplasm describes that growth as abnormal and uncontrolled.

Myeloproliferative Neoplasms/Hematopoietic pluripotent stem cells have self-renewal capability and give rise to either myeloid or the lymphoid lineage which further differentiates into various mature blood cells such as red blood cells (RBC), lymphocytes, granulocytes, megakaryocytes, and macrophages. The hematopoietic process is determined by the bone marrow environment, growth factors, and transcription factors.

The abnormal proliferation of one or more terminal myeloid cell lines in the peripheral blood gives rise to a heterogeneous group of disorders called myeloproliferative neoplasms. In 1951, William Dameshek coined the term myeloproliferative disorders which are now reformed to myeloproliferative neoplasms (MPNs) by the World Health Organization (WHO). Chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are four classic types of myeloproliferative neoplasms. WHO classification also included chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia (CEL), and MPN, unclassifiable. Out of the classic types of MPNs, CML is BCR-ABL1 positive, but PV, ET, and PMF are BCR-ABL1 negative. Besides, the fourth edition of WHO classification for myeloid and acute leukemia was revised in 2016 due to recent advances in hematology with the identification of molecular markers and prognostic markers, giving a better understanding of the molecular pathogenesis and genetics of the hematological malignancies.

Types of Myeloproliferative Neoplasms

The types are
  • Chronic myeloid leukemia – It comprises 0.5% of all new cancer cases in the United States. As per recent SEER (Surveillance, Epidemiology, and End Results) national cancer database from the US, CML is commonly diagnosed in older age groups, ranging from 65 to 74 years, and the median age of diagnosis is 65 years. It is more common in males, with an incidence rate of about 2.4 new cases per 100,000 versus 1.4 new cases per 100,000 in females. About 67.6% of patients have a 5-year survival rate, and the median age of death is about 77 years.
  • Polycythemia vera The median age of diagnosis of PV is 60 years. It is more prevalent in males as compared to females, with a male to female ratio of 1.8: 1. The estimated incidence of PV ranges from 0.4 to 2.8 per 100,000 per year.
  • Primary myelofibrosis – The median age at the diagnosis is 67 years. The incidence rate varies from 0.8 to 2.1/100,000/year. Other MPNs such as CNL, CEL, and unclassified MPN are rare; exact incidence and prevalence are not known due to the rarity of the disorders.
  • Essential thrombocythemia (ET) – PB findings are significant for thrombocytosis (450 X 10^9/L or higher) with platelet anisocytosis. In post-ET myelofibrosis, PB is notable for leukoerythroblastosis, with teardrop-shaped RBCs and poikilocytosis. The BM aspiration and biopsy show mild hypercellularity without any dyserythropoiesis, macrocytosis, and dysgranulopoiesis.
  • Chronic neutrophilic leukemia (CNL) PB is characterized by leukocytosis (WBC 25 X 10^9/L) with segmented or band neutrophils (80% or higher), few neutrophil precursors (less than 10%), and rare myeloblasts. The BM aspirate and biopsy demonstrates hypercellularity and mature granulocytosis with normal maturation and no dysgranulopoiesis.
  • Chronic eosinophilic leukemia (CEL)  Characterized by peripheral eosinophilia (1,500/uL or higher), BM with elevated eosinophils, myeloblasts less than 20% and a clonal abnormality.
According to WHO diagnostic criteria published in 2016, myeloproliferative neoplasms are diagnosed as follows
  • Chronic myeloid leukemia – Chronic myeloid leukemia (CML) has a presence of the hallmark Philadelphia Chromosome (BCR-ABL1) mutation.
  • Chronic neutrophilic leukemia – Chronic neutrophilic leukemia (CNL) is characterized by a mutation in the CSF3R gene and an exclusion of other causes of neutrophilia.
  • Essential thrombocythemia – Essential thrombocythemia (ET) is diagnosed with a platelet count greater than 450 × 109/L and is associated with the JAK2 V617F mutation in up to 55% of cases[8] and with an MPL (thrombopoietin receptor) mutation in up to 5% of cases:[9]. There should be no increase in reticulin fibers and the patient should not meet the criteria for other MPNs, in particular Pre-PMF.
  • Polycythemia vera – Polycythemia vera (PV) is associated most often with the JAK2 V617F mutation in greater than 95% of cases, whereas the remainder have a JAK2 exon 12 mutation. High hemoglobin or hematocrit counts are required, as is a bone marrow examination showing “prominent erythroid, granulocytic and megakaryocytic proliferation with pleomorphic, mature megakaryocytes.”
  • Prefibrotic/early primary myelofibrosis – Prefibrotic primary myelofibrosis (Pre-PMF) is typically associated with JAK2, CALR, or MPL mutations and shows reticulin fibrosis no greater than grade 1. Anemia, splenomegaly, LDH above the upper limits and leukocytosis are minor criteria.
  • Overtly fibrotic myelofibrosis – Like pre-PMF, overt primary myelofibrosis is associated with JAK2, CALR, or MPL mutations. However, a bone marrow biopsy will show reticulin and/or collagen fibrosis with a grade 2 or 3. Anemia, splenomegaly, LDH above the upper limits and leukocytosis are minor criteria.
  • MPN-U – Patients with otherwise unexplained thrombosis and with neoplasms that can’t be classified in one of the other categories.

According to Cancer. govt,  There are 6 types of chronic myeloproliferative neoplasms.

The type of myeloproliferative neoplasm is based on whether too many red blood cells, white blood cells, or platelets are being made. Sometimes the body will make too many of more than one type of blood cell, but usually one type of blood cell is affected more than the others are. Chronic myeloproliferative neoplasms include the following 6 types:

  • Chronic myelogenous leukemia.
  • Polycythemia vera.
  • Primary myelofibrosis (also called chronic idiopathic myelofibrosis).
  • Essential thrombocythemia.
  • Chronic neutrophilic leukemia.
  • Chronic eosinophilic leukemia.

These types are described below. Chronic myeloproliferative neoplasms sometimes become acute leukemia, in which too many abnormal white blood cells are made.


In the last decade, the treatment paradigm has changed with the detection of new driver mutations and a better understanding of the molecular pathogenesis of the MPNs. Mutations are divided into “restricted” which are found only in MPNs and “unrestricted” which are also detected in other myeloid malignancies; these mutations in hematopoietic stem cells (HSC) result in the clonal expansion of all myeloid cells, B cell, and natural killer cells, leading to MPNs.

Cytogenetics of CML is characterized by a reciprocal translocation between long arms of chromosomes 22 and 9, leading to the shortening of the length of the chromosome 22, also known as Philadelphia chromosomes, which is diagnostic of CML. The translocation involves the fusion of breakpoint cluster gene (BCR) on chromosome 22 with oncogene Abelson murine leukemia virus (ABL) on the long arm of chromosome 9 resulting in BCR-ABL fusion gene. The tyrosine kinase activity of the ABL oncogene is further enhanced with the fusion of BCR gene due to an encoding of a chimeric protein from BCR-ABL fusion gene.

In BCR-ABL1 negative MPNs, the restricted driver mutations are JAK2, myeloproliferative leukemia virus proto-oncogene (MPL), CALR, and CSF3R, which encodes for various tyrosine kinases.

  • Janus kinase (JAK) 2 gene mutationJanus kinase gene is a type of protein kinase that phosphorylates signal transducer and activator of transcription (STAT) in the JAK-STAT pathway, and activation of this pathway results in the pathogenesis of the MPNs. The JAK2 mutation is found in about 70% of MPNs. It is a somatic mutation that involves the substitution of valine to phenylalanine at codon 617 (JAK2 V617F) in the pseudokinase domain. The frequency of JAK2 V617F mutation is 95% in patients with PV, about 50% to 70% in ET, and 40% to 50% in PMF, respectively.  In 5% of PV with JAK2 V617F negative individuals, JAK2 exon 12 mutation is found; however, no such mutation was found in ET and PMF.
  • MPL proto-oncogene mutation – The MPL gene codes the thrombopoietin (TPO) receptor which regulates megakaryopoiesis through a JAK-STAT pathway. The most common somatic MPL mutations are MPL W515L and MPL W515K which cause spontaneous activation of the JAK-STAT pathway, resulting in abnormal hematopoietic cell proliferation. These mutations are found in up to 6% of ET and up to 10% of PMF as per literature. Furthermore, this mutation will help categorize patients diagnosed with negative JAK2 V617F mutation and Philadelphia chromosome MPN. MPL mutations increase the risk of thrombotic complications as compared to JAK2 V617F mutation patients and are associated with low hemoglobin, low bone marrow (BM) cellularity, high platelets, and high serum erythropoietin levels.
  • Calreticulin (CALR) gene mutation  The CALR gene is located in chromosome 19 (exon 9) which encodes calreticulin, a calcium-binding endoplasmic reticulum chaperone protein that regulates cellular proliferation, differentiation, and apoptosis; this protein also plays a role in immune system function and wound healing. In 2013, the somatic mutation (usually frameshift mutation) of the CALR gene was discovered in patients with ET and PMF who were negative for JAK2 and MPL mutation. The CALR exon 9 mutations are found in approximately 50% to 75% of patients with ET and PMF.About 10% to 15% of ET and PMF patients lack all three driver mutations (JAK2 V617F, MPL W515L/K, and CALR exon 9), which are also known as triple-negative MPN.
  • Chronic neutrophilic leukemia (CNL) – is one of the myeloproliferative neoplasms which is characterized by peripheral leukocytosis with neutrophilia, hypercellularity of the BM with less than 5% myeloblasts, and normal neutrophil maturation. The JAK2 V617F mutation is common in CNL; however, detection of mutation in colony-stimulating factor 3 receptor (CSF3R) gene is one of the WHO diagnostic criteria for CNL and commonly occurs at a CSF3R T618I location in the gene.
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Causes of Myeloproliferative Neoplasms

  • The exact etiology of MPNs is not known; however, patients with a genetic mutation (Janus kinase 2) are associated with a higher risk of developing MPNs. In addition, exposure to a higher level of ionizing radiation and toxins such as benzene has been associated with an increase in the risk for development of MPNs.
  • MPNs arise when precursor cells (blast cells) of the myeloid lineages in the bone marrow develop somatic mutations which cause them to grow abnormally. There is a similar category of disease for the lymphoid lineage, the lymphoproliferative disorders acute lymphoblastic leukemia, lymphomas, chronic lymphocytic leukemia and multiple myeloma.

Symptoms of Myeloproliferative Neoplasms

The increase in red blood cells can cause the blood to thicken and clot, causing signs and symptoms of polycythemia vera. In early stages, patients may have few symptoms. As the disease progresses, the following symptoms may appear:

  • Blood clot
  • Fatigue
  • Headache
  • Excessive sweating
  • Blurred vision or blind spots
  • Weakness
  • Dizziness
  • Itchiness, especially after a warm shower or bath
  • Redness or a purplish appearance of skin
  • Peptic ulcers
  • Bloating or a feeling of fullness due to an enlarged spleen
  • Congestive heart failure or angina
  • Gout/inflammation of joints

Diagnosis of Myeloproliferative Neoplasms

The following tests and procedures may be used:

  • Physical exam and health history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
    • The number of red blood cells and platelets.
    • The number and type of white blood cells.
    • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
    • The portion of the blood sample made up of red blood cells.

    Complete blood count (CBC) with differential – A procedure in which a sample of blood is drawn and checked for the following:

    Peripheral blood smear – A procedure in which a sample of blood is checked for the following:

    • Whether there are red blood cells shaped like teardrops.
    • The number and kinds of white blood cells.
    • The number of platelets.
    • Whether there are blast cells.
  • Blood chemistry studies – A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.
  • Bone marrow aspiration and biopsy – The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for abnormal cells.
  • Cytogenetic analysis – A laboratory test in which the chromosomes of cells in a sample of bone marrow or blood are counted and checked for any changes, such as broken, missing, rearranged, or extra chromosomes. Changes in certain chromosomes may be a sign of cancer. Cytogenetic analysis is used to help diagnose cancer, plan treatment, or find out how well treatment is working.
  • Gene mutation test – A laboratory test done on a bone marrow or blood sample to check for mutations in JAK2MPL, or CALR genes. A JAK2 gene mutation is often found in patients with polycythemia vera, essential thrombocythemia, or primary myelofibrosis. MPL or CALR gene mutations are found in patients with essential thrombocythemia or primary myelofibrosis.
  • Chronic myeloid leukemia (CML) – Patient may be asymptomatic with an abnormal blood test, but common clinical manifestations include easy fatiguability, anorexia, weight loss, generalized malaise, sweating, abdominal discomfort or pain, abdominal fullness, early satiety, easy bruising, and bleeding. Physical examination may be positive for pallor, ecchymoses, and hepatosplenomegaly. In addition, priapism and sweet syndrome are rare findings.
  • Polycythemia vera (PV) Patients with PV have increased red cell mass which contributes to hyperviscosity, hypoxia, and thrombosis. Clinical manifestations of PV include headache, dizziness, visual disturbances, pruritus, malaise, tinnitus, paresthesia, erythromelalgia, abdominal pain, loss of appetite, weight loss, bleeding, and symptoms related to thrombosis. Patients often present with aquagenic pruritus, which is itching/stinging or burning sensation after warm bath or shower. Physical findings may include hepato-splenomegaly, facial plethora, superficial thrombophlebitis, gouty arthritis, conjunctival injection, and hypertension.
  • Essential thrombocythemia (ET) – Clinical symptoms of ET varies from asymptomatic presentation to symptoms due to thrombosis, bleeding, and vasomotor symptoms. Common symptoms include a headache, dizziness, visual changes, paresthesia, fatigue, and easy bruising. Microvascular occlusions involving vessels of distal extremities may cause erythromelalgia and gangrene. A patient may present with stroke symptoms due to thromboembolic complications. Physical examination findings may include splenomegaly, which is more common than hepatomegaly.
  • Primary myelofibrosis (PMF) The common symptoms include fatigue, night sweats, low-grade fever, early satiety, weight loss, abdominal fullness or discomfort, dysuria, hematuria, gastrointestinal (GI) bleeding, arthralgia, and bony pain. PMF is characterized by extramedullary hematopoiesis and BM fibrosis. Physical examination findings include pallor, petechiae, ecchymoses, splenomegaly, hepatomegaly, lymphadenopathy, pleural effusion, pericardial effusion, ascites, pulmonary edema, seizure, altered mental status, and spinal cord compression.
  • Chronic neutrophilic leukemia (CNL)  Most patients are asymptomatic, but common symptoms on presentation include fatigue, night sweats, loss of appetite, weight loss, easy bruising, and bone pain. A patient may have splenomegaly at diagnosis on physical examination.

The laboratory workup for the evaluation of MPNs includes the following

  • Complete blood count with differential
  • Peripheral blood with microscopic examination
  • Comprehensive metabolic panel
  • Electrolytes
  • Peripheral blood fluorescence in situ hybridization (FISH) or Reverse transcription-polymerase chain reaction (RT-PCR) for BCR-ABL1
  • Leukocyte alkaline phosphatase (LAP) score which helps to differentiate between reactive leukocytosis from CML. The LAP score is low in patients with CML and paroxysmal nocturnal hemoglobinuria, however, the score is high in leukemoid reaction.
  • Serum uric acid
  • Lactate dehydrogenase (LDH)
  • Erythropoietin (EPO) level – normal or high in secondary polycythemia, but low or normal in PV.
  • Von Willebrand factor – PV patients may develop acquired von Willebrand disease with platelet counts greater than 1 million/microL, and these patients are at increased risk of bleeding, particularly if they are on aspirin.
  • Bone marrow aspiration and biopsy
  • Cytogenetic analysis of the BM aspirate for Philadelphia Chromosome. FISH for bcr-abl. 
  • Peripheral blood molecular testing for JAK2, MPL, CALR, and CSF3R mutations.

Evaluation of MPNs involves comprehensive hematological/laboratory workup, BM biopsy, cytogenetic analysis, and clinical assessment. Owing to recent advances in molecular markers or driver mutations, 2008 WHO classification of myeloid neoplasm was updated in 2016 to incorporate new molecular biomarkers. Diagnostic criteria for MPNs based on revised and updated WHO classification are as follows

WHO diagnostic criteria for CML (Accelerated and Blast Phase)

The diagnosis of the CML requires any one or more of the following for the accelerated phase:

  • Persistent or increasing WBC (greater than 10 X 10^9/L), Unresponsive to therapy
  • Persistent thrombocytosis (greater than 1000 X 10^9/L), Unresponsive to therapy
  • Persistent thrombocytopenia (greater than 100 X 10^9/L), Unrelated to therapy
  • Persistent or increasing splenomegaly, Unresponsive to therapy
  • Basophils greater than or equal to 20% in peripheral blood
  • Blast cells 10% to 19% in peripheral blood or bone marrow
  • Additional clonal chromosomal abnormality in Philadelphia positive cells at diagnosis
  • Any new clonal chromosomal abnormality in Philadelphia positive cells during therapy

The diagnosis criteria for CML (blast phase) includes any one of the above criteria and blast cells greater than or equal to 20% in peripheral blood or BM or extramedullary involvement of lymph nodes, skin, lung, central nervous system, and bone.

Revised WHO Diagnostic Criteria for Polycythemia Vera

Diagnosis of PV necessitates the presence of either all three major criteria or the first two major criteria and one minor criterion.

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Major criteria
  • Hemoglobin greater than 16.5 g/dL in male and hemoglobin greater than 16.0 g/dL in female ORHematocrit greater than 49% in male and hematocrit greater than 48% in female ORIncreased red cell mass greater than 25% above mean normal predicted value
  • Bone marrow biopsy with trilineage myeloproliferation (panmyelosis) and hypercellularity for age
  • Presence of JAK2 V617F or JAK exon 12 mutation
Minor criterion
  • Serum erythropoietin below normal

Of note, patients with PV who fulfill the diagnostic criteria should also be evaluated for secondary causes of polycythemia.

Revised WHO Diagnostic Criteria for Essential Thrombocythemia

Diagnosis of ET requires either the presence of all four major criteria or the first three major criteria and the minor criterion.

Major criteria
  • Platelet count greater than or equal to 450 X 10^9/L
  • Bone marrow biopsy with a proliferation of megakaryocyte lineage with increased numbers of large, mature megakaryocytes. No increase in neutrophil granulopoiesis or erythropoiesis.
  • Not meeting WHO criteria for BCR-ABL1 positive CML, PMF, PV, MDS, or other myeloid neoplasms
  • Detection of JAK2CALR, or MPL mutation
Minor criterion
  • Presence of clonal marker or absence of evidence for reactive thrombocytosis
Revised WHO Diagnostic Criteria for Primary Myelofibrosis

The diagnosis of PMF requires the presence of all three major criteria and at least one of the minor criteria.

Major criteria
  • Bone marrow findings of megakaryocyte proliferation with atypia, usually accompanied by reticulin and/or collagen fibrosis
  • Not meeting the WHO criteria for BCR-ABL1 positive CML, ET, PV, MDS, or other myeloid neoplasms
  • Detection of JAK2CALR, or MPL mutation or presence of clonal markers in the absence of these mutations
Minor criteria
  • Anemia not attributed to another comorbid condition
  • Leukocytosis greater than or equal to 11 X 10^9/L
  • Palpable splenomegaly
  • Elevated LDH
  • Leukoerythroblastosis
Revised WHO diagnostic criteria for Chronic Neutrophilic Leukemia
  • Peripheral blood with WBC greater than or equal to 25 X 10^9/L, segmented neutrophils plus band forms greater than or equal to 80% of WBCs, neutrophil precursors less than 10%, rare myeloblasts, monocyte count less than 1 X 10^9/L, and no dysgranulopoiesis
  • Bone marrow hypercellularity with elevated neutrophil granulocytes, normal neutrophil maturation, and myeloblast less than 5% of nucleated cells
  • Not meeting WHO criteria for BCR-ABL1 positive CML, ET, PV, or PMF
  • No rearrangement of PDGFRA, PDGFRB, or FGFR1, or PCM1-JAK2
  • Detection of CSF3R T618I or other activating CSF3R mutation or in the absence of a CSF3R mutation sustained neutrophilia for at least 3 months, splenomegaly and no identifiable cause of reactive neutrophilia including an absence of a plasma cell neoplasm

Treatment of Myeloproliferative Neoplasms

Management or treatment of the different MPNs are as follows:

  • Chronic myeloid leukemia (CML)Philadelphia chromosome is the BCR-ABL1 fusion gene which results in dysregulated tyrosine kinase activity. Tyrosine kinase inhibitors (TKI) targets tyrosine kinase activity of the BCR-ABL1 fusion gene. CML is divided into three phases: chronic phase accelerated phase and blast phase. Patients with chronic phase are managed initially with TKIs such as imatinib (first-generation TKIs) or nilotinib and dasatinib (second-generation TKIs). Based on ENESTND and DASISION, Nilotionib and Dasatinib respectively were superior to Imatinib in terms of achieving cytogenetic and molecular remission.  Patients in accelerated phase are treated with second-generation TKI and depending upon response may need hematopoietic stem cell transplantation (HCT). However blast phase CML patients undergo treatment with TKI and are evaluated for stem cell transplant.
  • Polycythemia vera (PV) Patients are divided into high risk and low risk based on age and thrombotic events which also guide the management approach. Patient with age less than or equal to 60 years old with no history of a thrombotic event are classified as low-risk PV, however, patients with greater than 60 years or those who have a history of thrombotic events are considered high-risk patients. Low-risk PV is usually managed with low dose aspirin and therapeutic phlebotomy to maintain hematocrit less than 45%. High-risk PV is managed with therapeutic phlebotomy, low dose aspirin and the use of first-line cytoreductive agents such as hydroxyurea, busulfan, or interferon alfa. For those patients who do not respond to the first-line cytoreductive agents, ruxolitinib (tyrosine kinase inhibitor) as second-line therapy may be beneficial. Patients who develop acquired von Willebrand disease should avoid aspirin due to the increased risk of bleeding. Symptoms such as pruritus and erythromelalgia are generally well controlled with low dose aspirin, but recalcitrant cases may benefit from cytoreductive agents or ruxolitinib.
  • Essential thrombocythemia (ET)  The management of patients with ET is based on vasomotor symptoms, and it also involves the prevention of complications such as hemorrhage and thrombotic events. Vasomotor symptoms are usually controlled with low dose aspirin. Patients with high risk (age greater than 60 or thrombotic event at any age with positive JAK2 V617F mutation) or intermediate risk (age greater than 60, negative JAK2 mutation, and no thrombotic event) are treated with a cytoreductive agent (hydroxyurea) and low dose aspirin. Very low or low risk includes patients 60 years or younger, with or without JAK2 mutation and no thrombotic event; these patients are managed based on the symptoms with either low-dose aspirin or clinical monitoring alone.
  • Primary myelofibrosis (PMF) Patients with Intermediate and high-risk disease with Myelofibrosis benefit from Ruxolitinib. Based on the COMFORT trials Ruxolitinib was helpful in reducing spleen volume and improving symptoms related to Myelofibrosis. Allogeneic hematopoietic cell transplantation is recommended in patients with the high-risk disease with the potential to cure. Asymptomatic, low-risk patients are managed with observation only.
  • Chronic neutrophilic leukemia (CNL) – Because of the rarity of the disease, there is no specific treatment. Most patients are managed with a cytoreductive agent (hydroxyurea).
There are different types of treatment for patients with chronic myeloproliferative neoplasms.
  • Eleven types of standard treatment are used:
    • Watchful waiting
    • Phlebotomy
    • Platelet apheresis
    • Transfusion therapy
    • Chemotherapy
    • Radiation therapy
    • Other drug therapy
    • Surgery
    • Immunotherapy
    • Targeted therapy
    • High-dose chemotherapy with stem cell transplant
  • New types of treatment are being tested in clinical trials.
  • Treatment for chronic myeloproliferative neoplasms may cause side effects.
  • Patients may want to think about taking part in a clinical trial.
  • Patients can enter clinical trials before, during, or after starting their cancer treatment.
  • Follow-up tests may be needed.

There are different types of treatment for patients with chronic myeloproliferative neoplasms.

Different types of treatments are available for patients with chronic myeloproliferative neoplasms. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Eleven types of standard treatment are used:

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until signs or symptoms appear or change.


Phlebotomy is a procedure in which blood is taken from a vein. A sample of blood may be taken for tests such as a CBC or blood chemistry. Sometimes phlebotomy is used as a treatment and blood is taken from the body to remove extra red blood cells. Phlebotomy is used in this way to treat some chronic myeloproliferative neoplasms.

Platelet apheresis

Platelet apheresis is a treatment that uses a special machine to remove platelets from the blood. Blood is taken from the patient and put through a blood cell separator where the platelets are removed. The rest of the blood is then returned to the patient’s bloodstream.

Transfusion therapy

Transfusion therapy (blood transfusion) is a method of giving red blood cells, white blood cells, or platelets to replace blood cells destroyed by disease or cancer treatment.


Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy).

See Drugs Approved for Myeloproliferative Neoplasms for more information.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. External radiation therapy uses a machine outside the body to send radiation toward the area of the body, such as the spleen, with cancer.

Other drug therapy

Prednisone and danazol are drugs that may be used to treat anemia in patients with primary myelofibrosis.

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Anagrelide therapy is used to reduce the risk of blood clots in patients who have too many platelets in their blood. Low-dose aspirin may also be used to reduce the risk of blood clots.

Thalidomide, lenalidomide, and pomalidomide are drugs that prevent blood vessels from growing into areas of tumor cells.

Erythropoietic growth factors are used to stimulate the bone marrow to make red blood cells.

See Drugs Approved for Myeloproliferative Neoplasms for more information.


Splenectomy (surgery to remove the spleen) may be done if the spleen is enlarged.


Immunotherapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This cancer treatment is a type of biologic therapy.

  • Interferon: Interferon affects the division of cancer cells and can slow tumor growth. Interferon alfa and pegylated interferon alpha are commonly used to treat certain chronic myeloproliferative neoplasms.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. Targeted therapies usually cause less harm to normal cells than chemotherapy or radiation therapy do.

  • Tyrosine kinase inhibitor (TKI) therapy: TKI therapy blocks signals that cancer cells need to grow. Ruxolitinib is used to treat polycythemia vera and certain types of myelofibrosis.

See Drugs Approved for Myeloproliferative Neoplasms for more information.

Other types of targeted therapies are being studied in clinical trials.

  • High-dose chemotherapy with stem cell transplant

    High doses of chemotherapy are given to kill cancer cells. Healthy cells, including blood-forming cells, are also destroyed by the cancer treatment. Stem cell transplant is a treatment to replace the blood-forming cells. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the patient completes chemotherapy, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body’s blood cells.

    Stem cell transplant.
    (Step 1): Blood is taken from a vein in the arm of the donor. The patient or another person may be the donor. The blood flows through a machine that removes the stem cells. Then the blood is returned to the donor through a vein in the other arm.
    (Step 2): The patient receives chemotherapy to kill blood-forming cells. The patient may receive radiation therapy (not shown).
    (Step 3): The patient receives stem cells through a catheter placed into a blood vessel in the chest.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today’s standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the website.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment of Chronic Myelogenous Leukemia

See the PDQ summary about Chronic Myelogenous Leukemia Treatment for information.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

Treatment of Polycythemia Vera

For information about the treatments listed below, see the Treatment Option Overview section.

The purpose of treatment for polycythemia vera is to reduce the number of extra blood cells. Treatment of polycythemia vera may include the following:

  • Phlebotomy.
  • Chemotherapy with or without phlebotomy. If the chemotherapy does not work, targeted therapy (ruxolitinib) may be given.
  • Immunotherapy (interferon alfa or pegylated interferon alpha).
  • Low-dose aspirin.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

Treatment of Primary Myelofibrosis

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of primary myelofibrosis in patients without signs or symptoms is usually watchful waiting.

Patients with primary myelofibrosis may have signs or symptoms of anemia. Anemia is usually treated with transfusion of red blood cells to relieve symptoms and improve quality of life. In addition, anemia may be treated with:

  • Erythropoietic growth factors.
  • Prednisone.
  • Danazol.
  • Thalidomide, lenalidomide, or pomalidomide, with or without prednisone.

Treatment of primary myelofibrosis in patients with other signs or symptoms may include the following:

  • Targeted therapy with ruxolitinib.
  • Chemotherapy.
  • Donor stem cell transplant.
  • Thalidomide, lenalidomide, or pomalidomide.
  • Splenectomy.
  • Radiation therapy to the spleen, lymph nodes, or other areas outside the bone marrow where blood cells are forming.
  • Immunotherapy (interferon alfa).
  • Erythropoietic growth factors.
  • A clinical trial of other targeted therapy drugs.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

Treatment of Essential Thrombocytopenia

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of essential thrombocythemia in patients younger than 60 years who have no signs or symptoms and an acceptable platelet count is usually watchful waiting. Treatment of other patients may include the following:

  • Chemotherapy.
  • Anagrelide therapy.
  • Immunotherapy (interferon alfa or pegylated interferon alpha).
  • Platelet apheresis.
  • A clinical trial of a new treatment.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

Treatment of Chronic Neutrophilic Leukemia

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of chronic neutrophilic leukemia may include the following:

  • Donor bone marrow transplant.
  • Chemotherapy.
  • Immunotherapy (interferon alfa).
  • A clinical trial of a new treatment.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

Treatment of Chronic Eosinophilic Leukemia

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of chronic eosinophilic leukemia may include the following:

  • Bone marrow transplant.
  • Immunotherapy (interferon alfa).
  • A clinical trial of a new treatment.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done.