Introduction:
Chronic myelomonocytic leukemia (CMML) originates in the cells within the bone marrow responsible for blood formation and spreads to the bloodstream. It is classified as a chronic myeloproliferative disorder, meaning the bone marrow produces an excessive amount of white blood cells, particularly monocytes.
What Is Bone Marrow?
Bone marrow is a type of tissue in bones: the skull, rib cage, pelvis, and spinal column. It is composed of cells that form blood, fat cells, and supporting tissues that aid in the growth of blood-forming cells. A small percentage of the blood-forming cells are unique types of cells referred to as stem cells. These cells are responsible for creating new cells. When a stem cell divides, it produces two cells: one cell that remains a stem cell and another cell that can continuously divide and form blood cells. There are three primary types of blood cells: red blood cells, white blood cells, and platelets.
1. Red blood cells, commonly referred to as erythrocytes, collect oxygen in the lungs and distribute it throughout the body. Anemia, a condition resulting from a scarcity of red blood cells, can lead to pallor, fatigue, and weakness.
2. White blood cells, commonly referred to as leukocytes, are vital in the defense against infections.
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Lymphocytes are immune cells found in the bone marrow, blood, and lymph nodes. Some kinds of lymphocytes produce antibodies that assist the body in fighting germs, while others directly kill invading germs by producing toxic substances that damage cells.
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Granulocytes are white blood cells that eliminate bacteria. They contain granules made up of enzymes and other substances that can destroy germs causing infections. Granulocytes are formed in the bone marrow from myeloblasts, which are immature cells. The neutrophil, the most prevalent type of granulocyte, plays a crucial role in combating bacteria. Other kinds of granulocytes include basophils and eosinophils. A shortage of neutrophils in the blood is known as neutropenia and can lead to severe infections.
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Monocytes are related to the granulocyte family and help protect the body against bacteria. The early cells in the bone marrow are called monoblasts. Macrophages can destroy germs and help lymphocytes recognize germs.
3. Platelets also referred to as thrombocytes, are a type of blood cell that stem from the megakaryocyte, a large cell in the bone marrow. Fragments of the megakaryocyte are released into the bloodstream as platelets, which are crucial for blood coagulation. A decrease in platelets is referred to as thrombocytopenia.
What Causes the Development of CMML?
CMML is a condition where a stem cell in the bone marrow undergoes a mutation and causes abnormal blood cell production. This leads to an overabundance of immature monocytes, a type of white blood cell which crowds out other blood cells. As a result, these immature monocytes cannot perform their normal functions. As a result, these abnormal monocytes accumulate in the bone marrow and other organs, hindering the normal production of other blood cells, including red blood cells, which transport oxygen to the body, and platelets, which help to stop bleeding. If left untreated, CMML can cause anemia, a weakened immune system, and an increased risk of bleeding and easy bruising.
What Are the Subtypes of CMML?
Doctors use a classification system created by the World Health Organization to classify the three subtypes of CMML based on the percentage of blast cells found in the blood and bone marrow. The three subtypes are
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CMML-0 has two percent blasts in the blood and five percent in the bone marrow.
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CMML-1 has two to four percent blasts in the blood and five to nine percent blasts in the bone marrow.
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CMML-2 has 5 to 19 percent blasts in the blood and 10 to 19 percent in the bone marrow.
CMML can be grouped into two subtypes based on white blood cell count:
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A dysplastic type (MD-CMML) with a WBC count less than 13x109/L.
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Proliferative type (MP-CMML) with a WBC count greater than or equal to 13x109/L.
What Are the Signs and Symptoms of CMML?
The symptoms of CMML can vary from person to person and depend on the specific subtype of the disease. For example, those with the myelodysplastic subtype (MD-CMML) typically experience low blood cell counts, including anemia, which can cause weakness, fatigue, bleeding and bruising due to low platelet counts. They may also have recurrent infections due to a lack of white blood cells. In contrast, individuals with myeloproliferative subtype (MP-CMML) generally have elevated levels of blood cells and may present with symptoms such as an enlarged spleen and liver, fatigue, night sweats, bone pain, and weight loss. Despite these symptoms resembling other benign conditions, it is advisable to seek medical attention if experiencing any of these symptoms.
How to Diagnose CMML?
To diagnose CMML, a series of tests are typically performed, including repeated blood and bone marrow tests. A single laboratory test result showing abnormal blood counts is not enough to confirm a diagnosis, so doctors will monitor patients over a period of time with repeated tests to eliminate other possible diagnoses. The bone marrow testing process involves: taking both a liquid marrow sample through aspiration and a small sample of bone filled with marrow through a biopsy, usually done simultaneously in a medical facility. To confirm a diagnosis and identify the specific type of CMML, a hematopathologist specialist will analyze samples of a patient's blood and bone marrow. First, the hematopathologist will look for certain characteristics, such as elevated levels of a specific type of white blood cell called monocytes and the absence of a particular genetic marker called the Philadelphia chromosome. Additionally, the hematopathologist will check for a limited number of immature blood cells, known as blast cells, and any abnormalities in the cells that give rise to red and white blood cells or platelets. Additional diagnostic tests that a doctor may order to diagnose CMML include:
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X-rays or CT scans to check for an enlarged spleen or liver.
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Blood and urine tests to detect high levels of lysozyme.
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Additional blood tests to check for high lactate dehydrogenase levels (LDH) and beta 2-microglobulin may indicate tissue damage or increased white-cell production or destruction due to inflammation or cancer.
What Are the Treatment Options for CMML?
In general, CMML cannot be completely cured but can be managed with various treatment options. Medical professionals use a range of treatments for adults with CMML, although there is no universally accepted therapy for the condition. The treatment options for CMML in adults include:
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Chemotherapy and other medications.
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Stem cell transplantation.
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Participation in clinical trials as a treatment option.
The doctor will take into account various factors when deciding on a treatment plan, such as:
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The type and severity of your symptoms.
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The pace at which the disease is advancing and the urgency to control it.
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Suitability for a stem cell transplant.
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Overall health condition.
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The potential impact of treatment on quality of life.
Are There Any Side Effects Associated With Treatment?
Chemotherapy drugs can cause side effects by damaging normal cells. In addition, the intensity of chemotherapy, medications used, and overall health can affect the side effects experienced. The common side effects of CMML treatment include:
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Extreme fatigue.
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Infections.
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Hair loss.
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Nausea and vomiting.
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Diarrhea.
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Constipation.
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Mouth sores.
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Low blood pressure.
Conclusion:
Chronic myelomonocytic leukemia (CMML) is a form of blood cancer that targets the bone marrow, the material in specific bones responsible for producing blood cells. It is a chronic myeloproliferative disorder, meaning that the bone marrow produces too many white blood cells, specifically monocytes. The symptoms of CMML can vary from person to person and depend on the specific subtype of the disease. Diagnosis of CMML involves a complete blood count and bone marrow biopsy. Treatment options include blood transfusions, medications, and stem cell transplantation.
