Chronic Monocytic Leukemia
Disease Details
Family Health Simplified
- Description
- Chronic monocytic leukemia is a type of leukemia characterized by the overproduction of monocytes, a type of white blood cell, in the bone marrow and blood.
- Type
- Chronic monocytic leukemia (CML) is classified as a type of chronic myelomonocytic leukemia (CMML). It typically occurs in adults rather than being inherited, so it is not generally associated with any specific type of genetic transmission. CMML can involve genetic mutations, but these typically arise spontaneously rather than being passed down through familial genetic inheritance.
- Signs And Symptoms
- The way CML presents depends on the stage of the disease at diagnosis as it has been known to skip stages in some cases.Most patients (~90%) are diagnosed during the chronic stage which is most often asymptomatic. In these cases, it may be diagnosed incidentally with an elevated white blood cell count on a routine laboratory test. It can also present with symptoms indicative of hepatosplenomegaly and the resulting left upper quadrant pain this causes. The enlarged spleen may put pressure on the stomach causing a loss of appetite and resulting weight loss. It may also present with mild fever and night sweats due to an elevated basal level of metabolism.Some (<10%) are diagnosed during the accelerated stage which most often presents bleeding, petechiae and ecchymosis. In these patients fevers are most commonly the result of opportunistic infections.Some patients are initially diagnosed in the blast phase in which the symptoms are most likely fever, bone pain and an increase in bone marrow fibrosis.
- Prognosis
- Before the advent of tyrosine kinase inhibitors, the median survival time for CML patients had been about 3–5 years from time of diagnosis.With the use of tyrosine kinase inhibitors, survival rates have improved dramatically. A 2006 follow-up of 553 patients using imatinib (Gleevec) found an overall survival rate of 89% after five years.A 2011 followup of 832 patients using imatinib who achieved a stable cytogenetic response found an overall survival rate of 95.2% after 8 years, which is similar to the rate in the general population. Fewer than 1% of patients died because of leukemia progression.
- Onset
- Chronic monocytic leukemia (CMML) typically has an insidious onset, meaning it develops gradually over time. Symptoms may be non-specific and can include fatigue, weight loss, fever, and night sweats. It is more common in older adults, usually those over 60 years old. The exact cause of CMML is not well understood, but it involves the abnormal growth of monocytes in the bone marrow.
- Prevalence
- Chronic monomonocytic leukemia (CMML) is a rare type of leukemia, falling under the category of myelodysplastic/myeloproliferative disorders. The prevalence is not precisely documented but is estimated at approximately 1 to 3 cases per 100,000 people annually. CMML predominantly affects older adults, typically those over the age of 60.
- Epidemiology
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There seems to be some confusion in your query regarding "nan." Please clarify this point so I can provide the most accurate information possible.
For now, I'll provide the epidemiology of chronic myelomonocytic leukemia (CMML):
### Epidemiology:
- **Incidence:** Chronic myelomonocytic leukemia (CMML) is a rare type of cancer. It predominantly affects older adults, with a median age at diagnosis around 65-75 years.
- **Gender:** The condition is more common in males compared to females.
- **Prevalence:** CMML accounts for approximately 1.8 per 100,000 people annually.
- **Risk Factors:** Advancing age, male gender, and exposure to certain chemicals and radiation are known risk factors.
If "nan" refers to any specific aspect of epidemiology or additional information, please specify so that I can assist you appropriately. - Intractability
- Chronic myelomonocytic leukemia (CMML) is typically considered a challenging disease to treat due to its nature as a type of cancer that arises from the bone marrow and involves both myelodysplastic and myeloproliferative features. Effective management often requires a combination of treatments, including supportive care, hypomethylating agents, chemotherapy, and potentially hematopoietic stem cell transplantation. While some patients may respond to these therapies, CMML can be resistant to treatment and may eventually progress, making it intractable in many cases. However, individual responses can vary, and advancements in treatment continually offer new possibilities.
- Disease Severity
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Disease severity:
Chronic Monocytic Leukemia (CML), specifically chronic myelomonocytic leukemia, often has a variable prognosis. The disease can range from relatively indolent with slow progression to more aggressive forms requiring intensive treatment. Prognosis can depend on factors such as patient age, overall health, and genetic mutations involved in the leukemia cells. - Healthcare Professionals
- Disease Ontology ID - DOID:8593
- Pathophysiology
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CML was the first cancer to be linked to a clear genetic abnormality, the chromosomal translocation known as the Philadelphia chromosome. This chromosomal abnormality is so named because it was first discovered and described in 1960 by two scientists from Philadelphia, Pennsylvania, US: Peter Nowell of the University of Pennsylvania and David Hungerford of Fox Chase Cancer Center.In this translocation, parts of two chromosomes (the 9th and 22nd) switch places. As a result, part of the BCR ("breakpoint cluster region") gene from chromosome 22 is fused with the ABL gene on chromosome 9. This abnormal "fusion" gene generates a protein of p210 or sometimes p185 weight (p210 is short for 210 kDa protein, a shorthand used for characterizing proteins based solely on size). Because abl carries a domain that can add phosphate groups to tyrosine residues (a tyrosine kinase), the bcr-abl fusion gene product is also a tyrosine kinase.
The fused BCR-ABL protein interacts with the interleukin 3beta(c) receptor subunit. The BCR-ABL transcript is continuously active and does not require activation by other cellular messaging proteins. In turn, BCR-ABL activates a cascade of proteins that control the cell cycle, speeding up cell division. Moreover, the BCR-ABL protein inhibits DNA repair, causing genomic instability and making the cell more susceptible to developing further genetic abnormalities. The action of the BCR-ABL protein is the pathophysiologic cause of chronic myelogenous leukemia. With improved understanding of the nature of the BCR-ABL protein and its action as a tyrosine kinase, targeted therapies (the first of which was imatinib) that specifically inhibit the activity of the BCR-ABL protein have been developed. These tyrosine kinase inhibitors can induce complete remissions in CML, confirming the central importance of bcr-abl as the cause of CML. - Carrier Status
- Chronic monocytic leukemia (CML) is not typically described in terms of carrier status because it is not an inherited disorder. Instead, it is a type of cancer that arises from genetic mutations acquired during a person's lifetime, particularly affecting monocytes, a type of white blood cell. Therefore, carrier status is not applicable for CML.
- Mechanism
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Chronic Monocytic Leukemia (CML) is a type of cancer that affects the blood and bone marrow. Here are the key aspects regarding its mechanisms and molecular mechanisms:
### Mechanism:
- CML typically progresses in distinct phases: the chronic phase, accelerated phase, and blast crisis.
- Chronic phase: The disease progresses slowly, with an increase in mature but abnormal white blood cells.
- Accelerated phase and blast crisis: CML becomes more aggressive, with an increase in immature white blood cells (blasts).
### Molecular Mechanisms:
- **Philadelphia Chromosome (Ph1)**: The hallmark of CML is the presence of the Philadelphia chromosome, which results from a reciprocal translocation between chromosomes 9 and 22, designated as t(9;22)(q34;q11).
- **BCR-ABL1 Fusion Gene**: This translocation creates a fusion gene called BCR-ABL1, which encodes a constitutively active tyrosine kinase enzyme.
- **Tyrosine Kinase Activity**: The BCR-ABL1 fusion protein continuously activates signal transduction pathways that promote uncontrolled cell division and inhibit DNA repair mechanisms and apoptosis, leading to the proliferation of leukemic cells.
- **Signaling Pathways**: The BCR-ABL1 kinase activates various downstream pathways, including the RAS/RAF/MEK/ERK and PI3K/AKT pathways, which contribute to cell proliferation, survival, and resistance to apoptosis.
Understanding these mechanisms has been key to developing targeted therapies, such as tyrosine kinase inhibitors (TKIs), which specifically inhibit the BCR-ABL1 protein, helping to control the progression of CML. - Treatment
- The only curative treatment for CML is a bone marrow transplant or an allogeneic stem cell transplant. Other than this there are four major mainstays of treatment in CML: treatment with tyrosine kinase inhibitors, myelosuppressive or leukapheresis therapy (to counteract the leukocytosis during early treatment), splenectomy and interferon alfa-2b treatment. Due to the high median age of patients with CML it is relatively rare for CML to be seen in pregnant women, despite this, however, chronic myelogenous leukemia can be treated with relative safety at any time during pregnancy with the cytokine interferon-alpha.
- Compassionate Use Treatment
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Chronic myelomonocytic leukemia (CMML) generally requires specialized treatments, and in cases where standard therapies are not effective or patients are ineligible for them, compassionate use, off-label, or experimental treatments may be considered. Here are some options:
1. **Hypomethylating Agents:** Drugs such as azacitidine and decitabine are commonly used off-label for CMML. They work by interfering with the DNA methylation in cancer cells.
2. **JAK2 Inhibitors:** Ruxolitinib is an example; though primarily used for myelofibrosis, it has shown some efficacy in CMML.
3. **FLT3 Inhibitors:** Agents like midostaurin can be used off-label, particularly for patients with FLT3 mutations, although they are not approved specifically for CMML.
4. **HDAC Inhibitors:** Histone deacetylase inhibitors like vorinostat have been studied in clinical trials and may be used in specific cases.
5. **Allogeneic Stem Cell Transplant:** This remains the only potential curative option for CMML, although it's not suitable for all patients.
6. **Clinical Trials:** Patients may be eligible for experimental treatments through clinical trials. New targeted therapies, combination strategies, and novel agents are constantly being evaluated.
It is important for treatment decisions to be individualized and overseen by a healthcare professional skilled in hematologic malignancies. - Lifestyle Recommendations
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Chronic Monocytic Leukemia (CML) is a type of cancer that affects the blood and bone marrow. Here are some lifestyle recommendations for managing CML:
1. **Healthy Diet**: Consuming a balanced diet rich in fruits, vegetables, lean proteins, and whole grains can help maintain overall health and support the immune system.
2. **Regular Exercise**: Engaging in regular physical activity can improve overall well-being, increase energy levels, and reduce fatigue commonly experienced in CML patients. Always consult with your healthcare provider before starting any new exercise regimen.
3. **Avoid Infections**: Since CML can weaken the immune system, it's crucial to take precautions to avoid infections. This includes practicing good hygiene, staying away from sick individuals, and getting recommended vaccinations (e.g., flu shots).
4. **Stress Management**: Techniques such as meditation, yoga, or deep-breathing exercises can help manage stress, which is beneficial for overall health and coping with the emotional aspects of living with CML.
5. **Regular Medical Checkups**: Follow your healthcare provider's advice for blood work and other diagnostic tests to monitor the disease's progression and response to treatment.
6. **Medication Adherence**: Taking prescribed medications as directed is essential for managing CML. Keep a medication schedule and use reminders if necessary.
7. **Adequate Rest**: Ensure you get enough sleep and rest, as fatigue is a common symptom of CML.
Consult with your healthcare provider for personalized advice and to develop a comprehensive care plan tailored to your specific needs. - Medication
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For chronic myelomonocytic leukemia (CMML), treatment options primarily include:
1. **Hypomethylating Agents:** Azacitidine and decitabine are often used to help control the disease.
2. **Chemotherapy:** Drugs like cytarabine may be used in some cases.
3. **Targeted Therapy:** The use of specific drugs like lenalidomide or certain tyrosine kinase inhibitors, if genetic mutations are present.
4. **Allogeneic Stem Cell Transplant:** In selected cases, especially for younger patients or those with high-risk disease.
Treatment plans should be personalized based on the patient's overall health, genetics of the leukemia, and physician recommendations. - Repurposable Drugs
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Chronic monocytic leukemia (CML) is relatively rare, and research into repurposable drugs for its treatment is ongoing. Repurposable drugs are existing medications for other conditions that may be effective against CML. Some drugs that have shown potential include:
1. **Ruxolitinib**: Originally used for myelofibrosis, it has shown some promise in targeting certain pathways involved in CML.
2. **Venetoclax**: Approved for chronic lymphocytic leukemia, it targets BCL-2 and may benefit some monocytic leukemia patients.
3. **Dasatinib**: A tyrosine kinase inhibitor primarily used for chronic myeloid leukemia, but also considered in cases of CML with certain mutations.
Repurposing drugs can offer a faster route to effective treatments, but always consult with a healthcare provider for the most appropriate therapy. - Metabolites
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In chronic monocytic leukemia (CMML), common metabolic concerns include elevated levels of certain metabolites due to the leukemic process. Key metabolites can include:
1. **Lactate** - Accumulation due to increased glycolytic activity.
2. **Uric Acid** - Increased turnover of nucleic acids from leukemic cells can lead to hyperuricemia.
3. **Cytokines** - Elevated levels of inflammatory cytokines can be observed.
4. **Creatinine** - May indicate renal involvement or dysfunction secondary to hyperuricemia or disease-related renal damage.
For accurate diagnosis and tailored metabolic profiling, it's essential to conduct comprehensive laboratory tests and consult healthcare providers. - Nutraceuticals
- Nutraceuticals have not been conclusively proven to treat or manage chronic monocytic leukemia (CMML). Patients should rely on evidence-based treatments and consult their healthcare provider before incorporating any nutraceuticals into their regimen.
- Peptides
- Chronic Myelomonocytic Leukemia (CMML) is a type of leukemia that primarily affects older adults. It is characterized by an overproduction of monocytes in the bone marrow and blood. Immunotherapeutic approaches involving peptides are being explored for various types of cancers, including leukemia, though CMML-specific peptide therapies are not widely established. Nanoparticle-based delivery systems (nanotechnology) are also being researched to improve the efficacy and targeting of leukemia treatments. These advanced therapies aim to enhance precision in treatment delivery while minimizing side effects.