Understanding CMML
Incidence
Signs and Symptoms
Diagnosis
Treatment
Clinical Trials
Outcomes
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Understanding CMML

Chronic myelomonocytic leukemia (CMML) is an uncommon blood cancer that has features of two other types of blood cancers. For this reason, the World Health Organization (WHO) classified CMML as a "mixed myelodysplastic/ myeloproliferative disease." This relatively new classification (2001) is expected to lead to a better understanding of the disease and to the development of more effective treatments.

CMML begins with one or more changes (mutations) to the DNA of a type of white cell called a "monocyte." When monocytes leave the blood and enter the tissues, they attack invading organisms, help combat infection and assist other blood cells, such as lymphocytes, in carrying out their immune functions. Monocytes arise from immature blood-forming cells called "myeloblasts" and "myelocytes."

In CMML, myeloblasts and myelocytes accumulate in the marrow and in other organs, interfering with the normal production of monocytes and other types of blood cells, including red blood cells and platelets. Monocytes represent about 5 to 10 percent of the cells in normal blood.

The World Health Organization categorized CMML into two subtypes according to the percentage of blast cells (blasts) found in the blood and marrow

• CMML-1 - Less than 5 percent blasts in the blood and less than 10 percent blasts in the marrow
• CMML-2 - 5 to 19 percent blasts in the blood and 10 to 19 percent blasts in the marrow

In most healthy individuals, blast cells represent less than 5 percent of developing marrow cells.

Incidence

It is estimated that CMML affects approximately 3 out of 100,000 individuals in the United States each year. The disease generally affects older adults. Seventy-five percent of patients are older than 60 years at the time of diagnosis and there are approximately twice as many male CMML patients as female CMML patients.

Signs and Symptoms

Signs and symptoms may include

• Weakness and fatigue due to low red cell counts (anemia)
• Petechiae (pinhead-sized sites of bleeding in the skin), bruising and bleeding due to low platelet counts (thrombocytopenia)
• Infections due to low white cell counts (leukopenia)
• Enlargement of the spleen and/or liver
• Feeling of fullness below the ribs due to spleen enlargement

Diagnosis

A CMML diagnosis generally cannot be confirmed after one lab test result shows abnormal blood counts. The diagnosis can only be confirmed after a patient has been monitored for a period of time with repeat lab tests to rule out other forms of myelodysplastic syndromes (MDS) or myeloproliferative disorders (MPDs).

The tests typically used in diagnosis include blood tests and bone marrow aspiration and biopsy to check for

• A persistent elevated monocyte count in the blood (greater than 1,000/microliter of blood)
• Less than 20 percent blasts in the blood or marrow
• Signs of abnormalities in one or more types of precursor cells that develop into red cells, certain types of white cells or platelets.

Other diagnostic tests may include

• X-rays and/or CT scans of the abdomen and pelvis to check for an enlarged spleen or liver
• Cytogenetic tests to confirm the absence of the Philadelphia (Ph) chromosome or the BCR-ABL rearrangement gene. The Ph chromosome is an abnormality of chromosome 22 found in the marrow and blood cells of CML patients
• Blood and urine tests to check for elevated "lysozyme" levels. Lysozyme is an enzyme found in saliva, tears and some immune cells such as monocytes
• Blood tests to detect elevated levels of proteins such as "lactate dehydrogenase" (LDH) and "beta 2-microglobulin." LDH levels may become elevated when there is tissue damage in the body. Beta 2-microglobulin may increase due to increased production or reduction of white cells, inflammation or certain types of cancer.

Genetic Mutations. Twenty to 40 percent of CMML patients have chromosomal abnormalities. About 1 to 4 percent of patients have an abnormality known as a translocation involving the PDGFR-B and TEL genes. In a translocation, a piece of one chromosome breaks off and attaches to another chromosome, which can lead to the development of a cancer gene (oncogene). Patients with the PDGFR-B and TEL gene mutation may respond favorably to treatment with the drug imatinib (Gleevec^®).

Treatment

For most CMML patients, the disease is treatable but not curable, with the therapies currently available. Patients are advised to seek treatment from a physician who is experienced in treating CMML or from a physician who is in consultation with a center or physician who has experience treating the disease.

The type of treatment depends on several patient factors, including the

• Nature and extent of symptoms
• Need for rapid disease control
• Eligibility for stem cell transplantation
• Overall health and quality of life.

Drug Therapy. There is no one standard treatment for CMML. Treatment for previously untreated or relapsed patients may include standard-dose or low dose cytarabine (Cytosar-U^®), etoposide (VePesid^®) and hydroxyurea (Hydrea^®). Treatment with these agents has been useful for a small number of patients.

Azacitidine (Vidaza^®) and decitabine (Dacogen^®), approved for treating MDS, are also approved for treating CMML. However, the effectiveness of these two agents for CMML treatment requires further study.

Imatinib (Gleevec^®) is used to treat the small percentage of patients who have the PDGFR-B and TEL gene mutation. This treatment usually leads to a return to normal blood counts, cytogenetic remissions and, occasionally, molecular remissions.

Stem Cell Transplantation. Allogeneic stem cell transplantation has been used to treat and sometimes cure CMML patients. This option is available to a small number of patients - generally younger patients who are not responding to therapy and who have an appropriate stem cell donor.

For more information about stem cell transplantation, please see the free LLS booklet Blood and Marrow Stem Cell Transplantation.

Clinical Trials

The goal of clinical trials for CMML is to improve treatment and quality of life and to increase survival. Patients are encouraged to talk to their physicians about whether taking part in a clinical trials would be a good treatment option for them. Patients can also call the Information Resource Center (IRC) for more information about clinical trials for CMML.

Therapies currently under study for CMML treatment include

• Decitabine (Dacogen^®) - studied for use in combination with other agents such as vorinostat (Zolinza^®) and arsenic trioxide (Trisenox^®)
• Fusion protein DT388 GM-CSF (granulocyte macrophage-colony stimulating factor)  - studies indicate that the fusion of DT388 (a toxin) with GM-CSF allows the targeting of cells with GM-CSF receptors, such as CMML cells
• Reduced-intensity allogeneic stem cell transplantation - an alternative for patients who do not respond to drug therapy and are not eligible for allogeneic stem cell transplants because of older age or other health risks.

Outcomes

Patients are advised to discuss survival information with their physicians. The reported median survival of individuals diagnosed with CMML is 12 to 24 months after the start of treatment. Keep in mind that outcome data can show how other people with CMML responded to treatment, but cannot predict how any one person will respond. Also, statistics may underestimate survival to a small degree since they may not reflect the most recent advances in treatment.

Many factors influence patient survival. Factors that may indicate a less favorable outcome include

• Severe anemia
• High blast percentage
• High total leukocyte (white cell) count
• High LDH level
• Larger spleen size

In about 20 percent of CMML patients, the disease progresses to acute myelogenous leukemia (AML).

Get More information

For more information about CMML, read or order online the free LLS fact sheet Chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML)

Contact Us

The Leukemia & Lymphoma Society
1311 Mamaroneck Ave.
White Plains, NY 10605

Email us at infocenter@LLS.org or call the Information Resource Center (IRC) at (800) 955-4572.