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Chronic Myelomonocytic Leukemia Samples

by | Aug 17, 2022 | News Releases | 0 comments

Bay Biosciences provides high quality, clinical grade, biopsy tissue samples, FFPE tissue blocks with matched cryogenically preserved K2EDTA plasma, sera (serum) and peripheral blood mononuclear cells (PBMC) biofluid samples from chronic myelomonocytic leukemia (CMML) patients.

The K2EDTA plasma, sera (serum) and PBMC biofluid specimens are processed from chronic myelomonocytic leukemia (CMML) patient’s peripheral whole-blood using customized collection and processing protocols.

Chronic Myelomonocytic Leukemia (CMML) Overview

Chronic myelomonocytic leukemia (CMML) is a rare type of blood cancer that disrupts the formation and activity of blood cells. Usually, leukemia affects leukocytes, or white blood cells. CMML is a rarer type of leukemia that affects myeloid stem cells in the blood marrow.

According to the American Cancer Society estimates, in United States CMML only occurs in 4 out of every 1 million patients per year, amounting to 1,100 new diagnosed cases each year.

The majority of people diagnosed with CMML are over the age of 60. CMML is also more common in men than in women.

These are stem cells that produce blood cells like:

  • Red blood cells (RBCs): These cells carry oxygen and other nutrients to the body’s organs and tissues.
  • White blood cells (WBCs): Also known as granulocytes and monocytes, these cells respond to infections and disease.
  • Platelets: These are the cells that form blood clots to help stop bleeding.

In CMML, there are too many monocytes in the blood. Monocytes are a type of white blood cell. In addition to higher-than-normal levels of monocytes, the patient might also have an increased number of immature WBCs, called blasts.

The overabundance of monocytes and blasts crowds out healthy blood cells like RBCs, platelets, and granulocytes. This leads to the symptoms of CMML.

The World Health Organization (WHO) has included CMML in a group of blood cancers called myeloproliferative and myelodysplastic disorders.

CMML is classified as a myelodysplastic disorder (MDS) and myeloproliferative neoplasm (MPN). This is because, while CMML is its own distinct condition, it shares features of two other conditions:

  • Myelodysplastic syndromes (MDS): It is a group of related blood conditions. When you have MDS, your blood cells are atypical and don’t develop properly, leading to fewer healthy blood cells. MDS can progress to acute myeloid leukemia (AML).
  • Myeloproliferative neoplasms (MPNs): MPNs are abnormal growths where your myeloid stem cells produce higher-than-normal levels of RBCs, WBCs, or platelets. These RBCs, WBCs, or platelets don’t function like they usually do. MPNs can also progress to AML.

 Myelodysplastic and Myeloproliferative Disorders

A myelodysplastic disorder is where the blood cells made are abnormal and not fully mature. A myeloproliferative disorder is a condition where there are too many blood cells made. In reality, the two disorders often overlap, which is why the WHO has put them together in the same category.

In CMML it is a specific type of white blood cells called monocytes that are abnormal. Monocytes are part of the immune system and help the body to fight infection. When too many monocytes are produced, and they are not developed enough to work properly. Monocytes take up a lot of space in the bone marrow therefore it is more difficult for the bone marrow to produce other blood cells such as:

  • Platelets
  • Red blood cells
  • White blood cells

Types of Chronic Myelomonocytic Leukemia (CMML)

World Health Organization (WHO) divides CMML into three different types. The three CMML groups are broken down by the percentage of blast cells that are present in the blood and bone marrow.

These percentages are based on the number of blasts per 100 WBCs:

  • CMML-0: Less than 2 percent blast cells in the blood and less than 5 percent blast cells in the bone marrow.
  • CMML-1: 2 to 4 percent blast cells in the blood or 5 to 9 percent blast cells in the bone marrow.
  • CMML-2: 5 to 19 percent blast cells in the blood and 10 to 19 percent blast cells in the bone marrow.

In addition to the three types above, WHO also classifies CMML based on WBC counts. There are two different types:

  • Dysplastic (MDS-CMML). WBC counts are less than 13×109 cells per liter.
  • Proliferative (MPN-CMML). WBC counts are greater than or equal to 13×109 cells per liter.

Signs and Symptoms of Chronic Myelomonocytic Leukemia (CMML)

Usually, CMML develops slowly over time, so the patients may not have symptoms early on in the disease. Because of this, it’s possible that the doctor may detect CMML when a routine blood test finds increased levels of monocytes or total white blood cells (WBCs).

The symptoms of CMML begin to happen when high levels of monocytes and blasts crowd out the patient’s healthy blood cells.

Following are the common signs and symptoms of CMML:

 

Causes and Risk Factors of Chronic Myelomonocytic Leukemia (CMML)

Exact causes of CMML are unknown. Scientists believe that genetic changes may cause the increased production of monocytes that’s seen in patients with this disease.

Potential risk factors for CMML include the following:

  • Male patients
  • Having certain genetic changes, such as those in the genes TET2, SRSF2, and ASXL1
  • Individuals over 60 years
  • Patients who have had previous treatment for cancer that included or radiation therapy
    chemotherapy.

Genetic Changes

Research has shown a number of genetic changes that are important in CMML.

Around half of all the people who have CMML have a change in a gene called TET2. The TET2 gene makes a protein that controls how many monocytes the stem cells make. Up to 30% have change in a gene called RAS. The change makes the cells multiply uncontrollably. Most CMML patients have more than one gene change.

There are other genes where changes might lead to CMML, these include:

  • ASXL1
  • SRSF2


Diagnosis of Chronic Myelomonocytic Leukemia (CMML)

To diagnose chronic myelomonocytic leukemia (CMML) your doctor will perform blood tests and bone marrow tests to be able to make a diagnosis.

Following are the several types of blood tests used to diagnose CMML:

  • Blood smear tests to evaluate the appearance of blood cells under a microscope
  • Complete blood count (CBC) test is performed to determine the number of monocytes and other blood cells in a blood sample
  • Other blood tests to help rule out other causes of elevated WBCs like infections or other health conditions

A bone marrow aspiration and biopsy are also performed, and the samples can be used to evaluate the following:

  • Percentage of cells that are blasts
  • Types, numbers, and appearance of blood cells
  • Observe certain genetic changes are present
  • Presence of specific markers on the surface of WBCs (immunophenotyping)

Diagnostic Criteria for Chronic Myelomonocytic Leukemia (CMML)

The World Health Organization (WHO) recommends the following criteria to diagnose CMML:

  • High monocyte levels (greater than or equal to 1×109 cells per liter) have increased for at least 3 months, with monocytes making up more than 10 percent of WBCs.
  • Blast cells make up less than 20 percent of cells in the blood or bone marrow, with no signs of AML.
  • Other specific conditions have been ruled out, including:
    • Leukemias with the Philadelphia gene fusion BCR-ABL1, which is a feature of chronic myeloid leukemia (CML) 
    • Other MPNs
    • Other blood cancers that can present with elevated levels of monocytes

 

Treatment of Chronic Myelomonocytic Leukemia (CMML)

Most patients are diagnosed with CMML because doctors find abnormal monocytes during a blood test for something else. If you have CMML, but aren’t experiencing symptoms, your doctor may choose to monitor your condition without treatment. This is called watchful waiting.

The type of treatment you need depends on:

  • The type of CMML
  • Whether the patient have symptoms
  • Age of the patient and whether they have any other medical conditions

Potential treatment options for CMML include:

Specific treatment plan for CMML will depend on many factors, including the following:

  • Type of CMML a patient has
  • The severity of the symptoms
  • Age of the patient
  • Your personal preference
  • Patient’s overall health


Stem Cell Transplant

A stem-cell transplant has the potential to cure CMML, but it can be very taxing on the body. Because of this, they’re typically only recommended for individuals that are younger in age and in good overall health.

During the stem cell transplant, a high dose of chemotherapy is used to kill cells in your bone marrow. Then, stem cells from a healthy matched donor are infused into your body. The goal is for these transplanted stem cells to reestablish healthy bone marrow.


Chemotherapy

Chemotherapy can also be used to treat CMML. While chemotherapy cannot cure CMML, it can kill cancer cells or slow their growth. Some examples of chemotherapy drugs that may be used to treat CMML include:

  • Decitabine (Dacogen)
  • Hydroxyurea (Hydrea)
  • Azacitidine (Vidaza)
  • Decitabine with cedazuridine (Inqovi)

Supportive Care

Supportive care is treatment that helps to reduce symptoms and prevent complications from CMML. Following some of the examples of CMML supportive care:

  • Antibiotics to help prevent or treat bacterial infections
  • Blood or platelet transfusions to help with low levels of RBCs or platelets
  • Erythropoiesis-stimulating agents like epoetin alfa (Procrit, Epogen) and darbepoetin (Aranesp) to promote the production of RBCs 

 

Outlook of Chronic Myelomonocytic Leukemia (CMML)

The outlook for CMML depends on the type of CMML that the patient has. Other things that can influence outlook include the following:

  • Blood cell counts
  • The presence of certain genetic changes
  • Patients age and overall health

It’s possible for CMML to come back (relapse) after treatment. Additionally, some types of CMML may not respond to treatment. This is called refractory CMML.

CMML progresses to AML in 15 to 30 percent of the patients. This happens when the number of blast cells in the patient’s blood or bone marrow goes higher than 20 percent.

Acute Myeloid Leukemia (AML) is an acute (rapidly growing) type of leukemia.

According to the American Cancer Society (ACS), research has shown that:

  • Patients with CMML-1 typically live longer than patients with CMML-2. Median life expectancy for CMML-1 and CMM-2 have been found to be 20 months and 15 months respectively.
  • About 20 percent of patients with CMML-1 and 10 percent of people with CMML-2 survive longer than 5 years after their diagnosis.
  • Patients with CMML-2 are more likely to progress to AML than those with CMML-1.

When discussing data like this, it’s important to remember that these statistics don’t reflect individual experiences. This data is based on many people with CMML over a long period of time.

Additionally, researchers continue to develop newer, more effective treatments for cancers like CMML. This can also improve the outlook for CMML overall.

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