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Myelofibrosis

Disease Details

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Description: Myelofibrosis is a rare bone marrow disorder that disrupts the body's normal production of blood cells, leading to extensive scarring in the bone marrow, severe anemia, fatigue, and an enlarged spleen.
Type: Myelofibrosis is a type of chronic leukemia, specifically a myeloproliferative neoplasm. It is generally not considered to be directly inherited. Instead, it typically arises from acquired mutations in certain genes, especially the JAK2, CALR, or MPL genes, rather than being passed from parent to child in a predictable genetic manner.
Signs And Symptoms: The primary feature of primary myelofibrosis is bone marrow fibrosis, but it is often accompanied by:

Abdominal fullness related to an enlarged spleen (splenomegaly).
Enlargement of both the liver and spleen
Splenomegaly due to extramedullary hematopoiesis (hematopoiesis occurring outside of the bone marrow)
Bone pain
Bruising and easy bleeding due to inadequate numbers of platelets
Increased risk of thrombosis
Cachexia (loss of appetite, weight loss, and fatigue)
Fatigue
Fevers
Chills
Weight loss
Gout and high uric acid levels
Increased susceptibility to infection, such as pneumonia
Pallor and shortness of breath due to anemia
Leukoerythroblastic smear (tear-drop RBCs, nucleated RBCs, and immature granulocytes)
In rarer cases, a raised red blood cell volume
Cutaneous myelofibrosis is a rare skin condition characterized by dermal and subcutaneous nodules.: 746
Prognosis: Myelofibrosis is a type of chronic leukemia that affects the bone marrow's ability to produce blood cells. The prognosis for myelofibrosis varies widely among individuals, depending on several factors such as age, general health, the extent of symptoms, and genetic mutations.

Generally, the prognosis can involve:

1. **Survival Rates**: Median survival varies but is typically around 5-7 years from diagnosis, though some patients may live much longer.
2. **Progression**: Myelofibrosis can progress to acute myeloid leukemia (AML) in some cases, which tends to have a worse prognosis.
3. **Symptoms Management**: Advances in treatment and management can improve quality of life and potentially prolong survival.

A thorough evaluation by a hematologist is necessary to determine the specific prognosis for an individual, considering all relevant variables.
Onset: The onset of myelofibrosis, a rare bone marrow disorder, can be variable. It often develops slowly over many years, with symptoms typically appearing in individuals in their 50s to 70s. In some cases, it can be asymptomatic in its early stages and detected incidentally through blood tests.
Prevalence: Myelofibrosis is a rare bone marrow disorder characterized by the replacement of bone marrow with fibrous scar tissue. The prevalence is estimated to be approximately 1.5 per 100,000 people.
Epidemiology: Myelofibrosis is a rare type of bone marrow cancer that disrupts the body's ability to produce blood cells. It is classified as a myeloproliferative neoplasm. The epidemiology of myelofibrosis includes:

1. **Incidence**: It is estimated to affect approximately 1-1.5 per 100,000 people annually.
2. **Age**: The median age at diagnosis is around 60-65 years, although it can occur in younger individuals as well.
3. **Gender**: It affects men and women equally.
4. **Geographic Distribution**: Myelofibrosis occurs worldwide without a clear geographic predilection.
5. **Risk Factors**: There are no specific environmental or lifestyle risk factors commonly associated with myelofibrosis. However, it can develop as a progression from other myeloproliferative disorders, such as polycythemia vera or essential thrombocythemia.

Understanding the epidemiology helps in recognizing patterns and guiding research and treatment strategies for myelofibrosis.
Intractability: Myelofibrosis can be considered intractable in the sense that it is a chronic condition with no known cure. However, treatments are available to manage symptoms, improve quality of life, and potentially slow disease progression. These may include medications, blood transfusions, and in some cases, stem cell transplantation.
Disease Severity: Myelofibrosis is a type of chronic leukemia that affects the bone marrow, leading to its scarring (fibrosis). The severity of myelofibrosis can vary widely among patients. It is generally classified into primary myelofibrosis (occurring on its own) and secondary myelofibrosis (evolving from other bone marrow disorders).

Disease severity is often assessed through factors like the degree of bone marrow fibrosis, blood counts, presence of symptoms (e.g., fatigue, spleen enlargement), genetic mutations, and overall patient health. The disease can progress from a relatively stable, chronic phase to a more severe and acute stage over time. In advanced stages, complications like severe anemia, increased risk of bleeding, and progression to acute myeloid leukemia can occur, making it life-threatening.

**Nan:** Not applicable.
Healthcare Professionals: Disease Ontology ID - DOID:4971
Pathophysiology: Myelofibrosis is a type of chronic leukemia that disrupts normal blood cell production. Pathophysiologically, it is characterized by the clonal proliferation of hematopoietic stem cells resulting in fibrotic tissue formation within the bone marrow, which impairs its ability to produce blood cells. This fibrosis is driven by abnormal cytokine release, particularly from mutated hematopoietic progenitors, with common genetic mutations including JAK2, MPL, and CALR. As the disease progresses, extramedullary hematopoiesis (blood cell production outside the bone marrow) occurs, leading to organomegaly, particularly in the spleen (splenomegaly) and liver (hepatomegaly).
Carrier Status: Myelofibrosis is not a condition associated with a carrier status. It is a rare type of bone marrow disorder that disrupts the body's normal production of blood cells, leading to extensive scarring in the bone marrow. It primarily develops spontaneously, although it can also be secondary to other bone marrow disorders. It is not typically inherited in a manner where an individual is considered a carrier.
Mechanism: Myelofibrosis is a clonal neoplastic disorder of hematopoiesis, the formation of blood cellular components. It is one of the myeloproliferative disorders, diseases of the bone marrow in which excess cells are produced at some stage. Production of cytokines such as fibroblast growth factor by the abnormal hematopoietic cell clone (particularly by megakaryocytes) leads to replacement of the hematopoietic tissue of the bone marrow by connective tissue via collagen fibrosis. The decrease in hematopoietic tissue impairs the patient's ability to generate new blood cells, resulting in progressive pancytopenia, a shortage of all blood cell types. However, the proliferation of fibroblasts and deposition of collagen is a secondary phenomenon, and the fibroblasts themselves are not part of the abnormal cell clone.In primary myelofibrosis, progressive scarring, or fibrosis, of the bone marrow occurs, for the reasons outlined above. The result is extramedullary hematopoiesis, i.e. blood cell formation occurring in sites other than the bone marrow, as the hemopoietic cells are forced to migrate to other areas, particularly the liver and spleen. This causes an enlargement of these organs. In the liver, the abnormal size is called hepatomegaly. Enlargement of the spleen is called splenomegaly, which also contributes to causing pancytopenia, particularly thrombocytopenia and anemia. Another complication of extramedullary hematopoiesis is poikilocytosis, or the presence of abnormally shaped red blood cells.Myelofibrosis can be a late complication of other myeloproliferative disorders, such as polycythemia vera, and less commonly, essential thrombocythemia. In these cases, myelofibrosis occurs as a result of somatic evolution of the abnormal hematopoietic stem cell clone that caused the original disorder. In some cases, the development of myelofibrosis following these disorders may be accelerated by the oral chemotherapy drug hydroxyurea.
Treatment: The one known curative treatment is allogeneic stem cell transplantation, but this approach involves significant risks.
Other treatment options are largely supportive, and do not alter the course of the disorder (with the possible exception of ruxolitinib, as discussed below). These options may include regular folic acid, allopurinol or blood transfusions. Dexamethasone, alpha-interferon and hydroxyurea (also known as hydroxycarbamide) may play a role.Lenalidomide and thalidomide may be used in its treatment, though peripheral neuropathy is a common troublesome side-effect.Splenectomy is sometimes considered as a treatment option for patients with myelofibrosis in whom massive splenomegaly is contributing to anaemia because of hypersplenism, particularly if they have a heavy requirement for blood transfusions. However, splenectomy in the presence of massive splenomegaly is a high-risk procedure, with a mortality risk as high as 3% in some studies.In November 2011, the US Food and Drug Administration (FDA) approved ruxolitinib (Jakafi) as a treatment for intermediate or high-risk myelofibrosis. Ruxolitinib serves as an inhibitor of JAK 1 and 2. Data from two phase III studies of ruxolitinib showed that the treatment significantly reduced spleen volume, improved symptoms of myelofibrosis, and was associated with much improved overall survival rates compared to placebo. However, the beneficial effect of ruxolitinib on survival has been recently questioned.In August 2019, the FDA approved fedratinib (Inrebic) as a treatment for adults with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF).In March 2022, the FDA approved pacritinib (Vonjo) with an indication to treat adults who have intermediate or high-risk primary or secondary myelofibrosis and who have platelet (blood clotting cells) levels below 50,000/µL.Momelotinib (Ojjaara) was approved for medical use in the United States in September 2023. It is indicated for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis [post-polycythemia vera and post-essential thrombocythemia], in adults with anemia.
Compassionate Use Treatment: For myelofibrosis, compassionate use treatments typically involve investigational drugs that have not yet been approved but may show potential benefit in clinical trials. These treatments are usually accessed when standard therapies are ineffective or unsuitable.

Off-label or experimental treatments for myelofibrosis include:

1. **Ruxolitinib (Jakafi)**: Approved for use in myelofibrosis, it may sometimes be used in combination with other agents off-label.
2. **Fedratinib (Inrebic)**: Another JAK2 inhibitor approved for myelofibrosis, sometimes explored for use in different combinations or settings.
3. **Interferon-alpha**: Used off-label for myelofibrosis, particularly in younger patients or those with less severe disease.
4. **Pacritinib**: A JAK2/FLT3 inhibitor in ongoing clinical trials. Used in certain cases under compassionate use.
5. **Momelotinib**: Another JAK1/JAK2 inhibitor under investigation that targets anemia and splenomegaly associated with myelofibrosis.
6. **Luspatercept**: This erythroid maturation agent is being studied for anemia management in myelofibrosis.
7. **Navitoclax**: A Bcl-2 inhibitor under clinical investigation for its potential to address fibrosis in myelofibrosis.
8. **PRM-151**: An anti-fibrotic agent in clinical trials aiming to reduce bone marrow fibrosis.

Each of these treatments is designed to target different aspects of myelofibrosis, from symptom management to altering the disease course, and their availability can vary based on clinical trial phases and regional regulatory approvals.
Lifestyle Recommendations: Lifestyle recommendations for individuals with myelofibrosis focus on managing symptoms and maintaining overall health. These steps include:

1. **Healthy Diet**: Consume a balanced diet rich in fruits, vegetables, whole grains, and lean proteins. Adequate nutrition supports overall health and helps manage symptoms like fatigue.

2. **Regular Exercise**: Engage in moderate physical activity as tolerated. Exercise can help improve energy levels, boost mood, and support cardiovascular health. Consult your healthcare provider before starting any new exercise regimen.

3. **Stay Hydrated**: Drink plenty of fluids to prevent dehydration, which can exacerbate symptoms.

4. **Rest and Manage Fatigue**: Prioritize rest and listen to your body. Plan activities to allow for periods of rest to manage fatigue effectively.

5. **Avoid Alcohol and Smoking**: Alcohol and smoking can interfere with blood cell production and exacerbate symptoms. Avoid these substances to improve your health outcomes.

6. **Infection Prevention**: Practice good hygiene, such as regular handwashing, and stay up-to-date with vaccinations to reduce the risk of infections, which can be more severe due to compromised immune function.

7. **Regular Medical Follow-ups**: Keep regular appointments with your healthcare provider to monitor disease progression and manage treatments effectively. Blood tests, symptom tracking, and adjustments to treatment plans may be necessary.

8. **Stress Management**: Utilize stress-reduction techniques such as meditation, yoga, or counseling to manage the emotional and psychological stress associated with chronic illness.

9. **Support Networks**: Engage with support groups or counseling services to connect with others who understand your condition and can offer support and advice.

These lifestyle adjustments can help improve quality of life and complement medical treatment for myelofibrosis. Always consult your healthcare provider for personalized advice.
Medication: For myelofibrosis, several medications can be used to manage symptoms and slow disease progression. These include:

1. **Ruxolitinib (Jakafi)** - A JAK2 inhibitor that helps to reduce spleen size and alleviate symptoms.
2. **Fedratinib (Inrebic)** - Another JAK2 inhibitor used for similar purposes as ruxolitinib.
3. **Hydroxyurea** - A chemotherapy drug used to manage high blood cell counts and spleen size.
4. **Thalidomide and lenalidomide** - Immunomodulatory drugs that can help some patients, especially those with anemia.
5. **Interferon-alpha** - Used in some cases to control blood counts and spleen size.

Treatment choice depends on individual patient factors, including symptom severity and risk stratification.
Repurposable Drugs: For myelofibrosis, some repurposable drugs that have shown potential include:

1. **Ruxolitinib (Jakafi)**: Although primarily approved for myelofibrosis, its reclassification for other myeloproliferative disorders highlights its repurpose potential.
2. **Thalidomide**: Initially developed as a sedative, it has found secondary use in myeloproliferative disorders for its anti-angiogenic properties.
3. **Lenalidomide (Revlimid)**: Originally for multiple myeloma, shown to have benefits in certain cases of myelofibrosis, especially when combined with other therapies.
4. **Danazol**: Known for treating endometriosis, it's sometimes used to manage anemia in myelofibrosis.
5. **Interferon-alpha**: Used for hepatitis C, it has immunomodulatory effects that can benefit myelofibrosis patients.

Further clinical trials and studies are ongoing to assess the efficacy and safety of these drugs in treating myelofibrosis.
Metabolites: In myelofibrosis, key abnormal metabolites include elevated levels of lactate dehydrogenase (LDH) due to increased cell turnover. Other abnormal findings can include altered cytokine levels, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), reflecting chronic inflammation and fibrosis. Elevated uric acid levels may also occur due to increased cellular breakdown.
Nutraceuticals: For myelofibrosis, the use of nutraceuticals is not a standard treatment approach. Myelofibrosis is a type of chronic leukemia that primarily affects the bone marrow, leading to severe anemia, weakness, fatigue, and spleen enlargement. Standard treatment usually involves medications, blood transfusions, and sometimes stem cell transplants.

There is limited evidence on the efficacy of nutraceuticals in myelofibrosis management. However, some patients use supplements to support overall health, under the supervision of a healthcare provider. These may include:

1. **Omega-3 fatty acids** - Anti-inflammatory properties.
2. **Vitamin D** - Bone health and immune support.
3. **Antioxidants (e.g., vitamin C, vitamin E)** - Potential to reduce oxidative stress.

Always consult with a healthcare professional before starting any nutraceutical regimen to ensure safety and proper management of myelofibrosis.
Peptides: In myelofibrosis, peptide-based treatments and nanotechnologies are emerging as promising areas of research. Peptides can potentially target specific pathways that drive the fibrosis in the bone marrow, aiming to inhibit the disease's progression. Nanotechnology, including the use of nanoparticles for drug delivery, is being explored to improve the efficacy and precision of treatments, potentially leading to better-targeted therapies with fewer side effects. These approaches are still largely in experimental stages but hold potential for future therapeutic strategies.