Myelodysplastic/myeloproliferative disease

Other Names: Myelodysplastic/myeloproliferative neoplasm

Myelodysplastic/myeloproliferative diseases are a group of diseases of the blood and bone marrow in which the bone marrow makes too many white blood cells. These disease have features of both myelodysplastic syndromes and myeloproliferative disorders. In myelodysplastic diseases, the blood stem cells do not mature into healthy red blood cells, white blood cells, or platelets and as a result, there are fewer of these healthy cells. In myeloproliferative diseases, a greater than normal number of blood stem cells develop into one or more types of blood cells and the total number of blood cells slowly increases.

Types

The 3 main types of myelodysplastic/myeloproliferative diseases include chronic myelomonocytic leukemia (CMML); juvenile myelomonocytic leukemia (JMML); and atypical chronic myelogenous leukemia (aCML). When a myelodysplastic/myeloproliferative disease does not match any of these types, it is called myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-UC).

Cause

In most cases, the cause of myelodysplastic/myeloproliferative disease is unknown, and there is limited information regarding potential causes. No specific genetic defects have been identified for any of the diseases.

The specific cause of chronic myelomonocytic leukemia (CMML) is unknown, but exposure to occupational and environmental carcinogens (agents that can cause cancer), ionizing radiation, and cytotoxic agents (agents that are toxic to cells) have been associated in some cases.

The cause of juvenile myelomonocytic leukemia (JMML) is not known; however, children with neurofibromatosis type 1 (NF1) are at increased risk for developing JMML, and up to 14% of cases of JMML occur in children with NF1.

Atypical chronic myelogenous leukemia (aCML) has been associated with cytogenetic (chromosomal) abnormalities in as many as 80% of individuals with the disease; however, no cytogenetic abnormality is specific.

Myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/ MPN-UC) (also known as mixed myeloproliferative/ myelodysplastic syndrome) also has no known cause.

Symptoms

Clinical symptoms are caused by complications resulting from the following:

• Cytopenia(s).
• Dysplastic cells that function abnormally.
• Leukemic infiltration of various organ systems.
• General constitutional symptoms, such as fever and malaise. (Refer to the PDQ summary on Hot Flashes and Night Sweats for more information on fever.)
• Patients with MDS/MPN do not have a Philadelphia chromosome or BCR/ABL fusion gene.

Clinical features of CMML include the following:

• Fever, fatigue, night sweats, and weight loss. (Refer to the PDQ summaries on Hot Flashes and Night Sweats, Fatigue, and Nutrition in Cancer Care for more information.)
• Infection.
• Bleeding caused by thrombocytopenia.
• Hepatomegaly (in some patients).
• Splenomegaly (in some patients).
• In patients with normal or slightly decreased white blood cell count, clinical features may be identical to MDS.
• In patients with elevated white blood cell count, features are more like chronic myeloproliferative disorders (CMPD), including more frequent splenomegaly and hepatomegaly.

The clinical features of JMML at the time of initial presentation may include the following:

• Constitutional symptoms (e.g., malaise, pallor, and fever) or evidence of an infection.
• Symptoms of bronchitis or tonsillitis (in approximately 50% of cases).
• Bleeding diathesis.
• Maculopapular skin rashes (in 40%–50% of cases).
• Lymphadenopathy (in approximately 75% of cases).
• Hepatosplenomegaly (in most cases).

Clinical features of aCML include the following:

• Anemia. (Refer to the PDQ summary on Fatigue for more information on anemia.)
• Thrombocytopenia.
• Splenomegaly (in 75% of cases).

Clinical characteristics of MDS/MPN-UC include the following:

• Features of both MDS and CMPD.
• Hepatomegaly.
• Splenomegaly.

Diagnosis

Tests that examine the blood and bone marrow are used to detect (find) and diagnose myelodysplastic/myeloproliferative neoplasms. The following tests and procedures may be used: Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease such as an enlarged spleen and liver. A history of the patient’s health habits and past illnesses and treatments will also be taken. Complete blood count (CBC) with differential: A procedure in which a sample of blood is drawn and checked for the following: 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 sample made up of red blood cells. Peripheral blood smear: A procedure in which a sample of blood is checked for blast cells, the number and kinds of white blood cells, the number of platelets, and changes in the shape of blood 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 a small piece of bone and bone marrow by inserting a needle into the hipbone or breastbone. A pathologist views both the bone and bone marrow samples 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. The cancer cells in myelodysplastic/myeloproliferative neoplasms do not contain the Philadelphia chromosome that is present in chronic myelogenous leukemia. Immunocytochemistry: A laboratory test that uses antibodies to check for certain antigens (markers) in a sample of a patient’s bone marrow. The antibodies are usually linked to an enzyme or a fluorescent dye. After the antibodies bind to the antigen in the sample of the patient's bone marrow, the enzyme or dye is activated, and the antigen can then be seen under a microscope. This type of test is used to help diagnose cancer and to tell the difference between myelodysplastic/myeloproliferative neoplasms, leukemia, and other conditions.

Treatment

There are different types of treatment for patients with myelodysplastic/myeloproliferative neoplasms. Five types of standard treatment are used:

• Chemotherapy
• Other drug therapy
• Stem cell transplant
• Supportive care
• Targeted therapy

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Imatinib mesylate (Brand name: Gleevec®)Treatment of adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor).

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