Myeloproliferative Neoplasms

Myeloproliferative Disorders (MPN)

Definition

• Myeloproliferative neoplasms (MPNs), also known as myeloproliferative disorders, are rare and potentially life-threatening blood cancers.
• Characterized by the body's overproduction of:
  • Red blood cells
  • White blood cells
  • Platelets
• The term "chronic" indicates a long-term condition.
• MPNs develop slowly, often over years, before symptoms become noticeable.
• Rarely, an MPN can transform into a more serious disease, such as acute leukemia.
• Treatments are available to alleviate symptoms and reduce the risk of disease progression.

Types of MPN

• The three most common types of MPNs are:
  • Polycythemia vera
  • Essential thrombocythemia
  • Primary myelofibrosis

Polycythemia Vera

• The most common type of MPN.
• Excess red blood cells thicken the blood, slowing its flow.
• Increased risk of blood clots, potentially leading to heart attack and stroke.
• In rare cases, polycythemia vera can progress to more serious blood diseases, including acute leukemia.

Myelofibrosis

• The most aggressive type of MPN.
• Bone marrow produces abnormal stem cells that become inflamed and create scar tissue.
• Over time, the bone marrow fills with scar tissue, impairing its ability to produce enough red blood cells, leading to anemia.
• Platelet production may also be reduced, affecting the body's ability to control bleeding.
• Some individuals with myelofibrosis may develop acute myeloid leukemia.

Essential Thrombocythemia

• The bone marrow produces an excessive number of platelets.
• Platelets form blood clots to stop bleeding when a blood vessel ruptures.
• In essential thrombocythemia, platelets are produced even when not needed, leading to an increased risk of blood clots, heart attack, and stroke.
• Symptoms develop very slowly, and the disease is often discovered during routine blood tests showing high platelet levels.
• Some individuals with essential thrombocythemia may develop leukemia.

Chronic Eosinophilic Leukemia (CEL)

• Involves the overproduction of white blood cells called eosinophils.
• Typically progresses slowly.
• In rare cases, CEL can transform into acute myeloid leukemia (AML).
• CEL is also known as hypereosinophilic syndrome.

Chronic Myelogenous Leukemia (CML)

• Involves the overproduction of white blood cells called granulocytes.
• Accumulation of these cells hinders the bone marrow's ability to produce other necessary blood cells.

Chronic Neutrophilic Leukemia (CNL)

• Involves an overproduction of white blood cells called neutrophils.

Myeloproliferative Neoplasm, Unclassifiable (MPN-U)

• A type of MPN that doesn’t fit into the other categories.
• It may involve an overproduction of various blood cell types, including white blood cells, red blood cells or platelets.

Risk Factors

• Age: MPNs are more common in people in their 50s, 60s, or older.
• Sex:
  • Polycythemia vera: More common in men and people assigned male at birth.
  • Essential thrombocythemia: More common in women and people assigned female at birth.
  • Other MPNs: Occur equally in both sexes.

Etiology

• MPNs are acquired genetic disorders.
• Mutations Associated with Janus Kinases (JAK):
  • Polycythemia vera, primary myelofibrosis, and essential thrombocythemia often involve genetic mutations associated with Janus kinase 2 (JAK2).
  • JAK2 mutation causes cells to multiply uncontrollably.

Diagnosis

Signs and Symptoms

• Many people have no symptoms in the early stages.
• As the condition progresses:
  • Splenomegaly: Enlargement of the spleen, causing fullness, pressure, or discomfort below the ribs on the left upper quadrant (LUQ).
  • While splenomegaly is a common symptom of most MPNs, it's less common in essential thrombocythemia.
  • Other symptoms depend on the specific type of MPN.

Lab Tests

• Complete Blood Count (CBC): Measures all blood cell levels.
  • Essential thrombocythemia: Evaluates platelet levels.
  • Polycythemia vera: Looks for increased hemoglobin (the protein in red blood cells), as well as white blood cells and platelets.
• Peripheral Blood Smear (PBS): Can reveal abnormal cell shapes that may indicate a condition.
• Blood Chemistry Tests:
  • Details the amount of specific chemicals in the blood (proteins, enzymes, glucose, etc.).
  • Provides clues about organ function, suggesting a possible MPN.
• Bone Marrow Biopsy:
  • Examines differences between normal and abnormal cells.
  • Identifies an unusual number of stem cells.
  • Detects changes in chromosomes and other signs of genetic mutations that may indicate a specific type of MPN.
• Genetic Testing: Analyzes blood cells for gene changes that may affect blood cell production.

Managements

• Allogeneic Stem Cell Transplantation: The only known cure for MPNs.
  • However, many individuals are ineligible due to the strenuous nature of the procedure.
• Other management strategies focus on:
  • Reducing the number of blood cells.
  • Providing symptom relief.
  • Preventing complications.
• Some treatments can lead to remissions.
• MPN treatments vary by type:
  • Chronic Eosinophilic Leukemia:
    • Reduce eosinophil levels with chemotherapy, corticosteroids, or immunotherapy.
  • Chronic Myelogenous Leukemia:
    • Targeted therapy to prevent cells from multiplying uncontrollably, chemotherapy, immunotherapy, radiation therapy, and stem cell transplants.
  • Chronic Neutrophilic Leukemia:
    • Chemotherapy, immunotherapy, and stem cell transplants.
  • Essential Thrombocythemia:
    • If asymptomatic, monitor the condition closely.
    • If symptomatic, treatments that prevent cells from multiplying out of control.
  • Primary Myelofibrosis:
    • If asymptomatic, closely monitor.
    • Treatments to address anemia, blood transfusions, medicines that stimulate the bone marrow.
    • Targeted therapy, chemotherapy, immunotherapy, radiation therapy, and stem cell transplant.

Prognosis

• Experiences vary based on factors such as the type of MPN, early diagnosis, and treatment response.
• With careful monitoring and treatment, many people live for several years.
• There is no single prognosis or expected outcome for these conditions.
• In general, many people diagnosed with MPN are alive five years later.

Survival Rates for Specific MPNs:

• Chronic Myelogenous Leukemia (CML):
  • The effectiveness of new targeted therapies has significantly increased the survival rate.
  • The five-year survival rate is 90%.
• Chronic Neutrophilic Leukemia and Polycythemia Vera:
  • With careful management, many people live 20 years, on average, following their diagnosis.
• Essential Thrombocythemia:
  • Many people live many years by taking medications that prevent blood clots.
• Primary Myelofibrosis:
  • Most people are still alive five to 10 years after a diagnosis.
• On their own, these aren’t fatal diseases, but some may cause life-threatening conditions such as heart attack or stroke.

Other Symptoms

• Chronic eosinophilic leukemia
  • The most common symptom is a rash. You may also feel tired and feverish. Other symptoms depend on what body parts are affected by your high eosinophil levels.
• Chronic myelogenous leukemia and chronic neutrophilic leukemia
  • Symptoms may include:
    • Bone pain
    • Night sweats
    • Fever and fatigue
    • Bruising easily
    • Loss of appetite and weight loss
• Essential thrombocythemia
  • Symptoms may include:
    • Bruising easily
    • Unexplained bruising or bleeding from your nose, mouth and gums
    • GI tract Bleeding
    • Hematuria
• Polycythemia vera
  • Symptoms may include:
    • Headaches
    • Dizziness
    • Fatigue
    • Blurred or double vision
• Primary myelofibrosis
  • anemia (fatigue, weakness, shortness of breath).
    • Pale skin
    • Night sweats
    • Fevers
    • Itchy skin
    • Abdominal fullness or filling up right away when you eat (early satiety)
    • Weight loss
    • Bone pain