Myelofibrosis and
Central Retinal Artery Occlusion
As far as I can find on Pubmed and Johns Hopkins list of all papers published, there are no case reports of Myelofibrosis causing Central Retinal Artery Occlusion (CRA). There are cases, though of Polycythemia Vera (PCV) causing CRAO. Likely cases of Myelofibrosis with CRAO have the same underlying issue as those with PCV
Here is what I found so far:
1.
A 60-year-old woman with no premorbidities presented with symptoms of sudden painless vision loss in the left eye (LE). Best-corrected visual acuity in the LE was counting fingers close to face. A relative afferent pupillary defect was observed in the LE. Ocular fundus examination of LE was suggestive of central retinal artery occlusion. Systemic evaluation revealed splenomegaly and normal cardiac and carotid arteries. Haematological investigations revealed increased haemoglobin, haematocrit, platelet count and leucocytosis with low erythrocyte sedimentation rate (ESR). Features of myeloproliferative neoplasm were noted on bone marrow aspiration. An assay for JAK2 mutation was positive. Since erythropoietin levels were normal, a diagnosis of primary polycythaemia vera was made and treated with aspirin and phlebotomy twice weekly until the target haematocrit of under 45% was achieved.
To report the case of a 49-year-old man who presented with profound visual loss in his right eye because of a central retinal artery occlusion, accompanied by a stroke in the ipsilateral middle cerebral artery with left upper extremity sequelae.
The patient underwent a comprehensive ophthalmologic examination, fluorescein angiography, thorough neuroophthalmology evaluation, including magnetic resonance imaging and magnetic resonance angiography, 12-lead electrocardiogram, transesophageal echocardiogram, bilateral carotid artery Doppler, Holter monitoring, comprehensive laboratory testing, bone marrow biopsy, and genetic testing.
Despite an initially normal hematocrit, the etiology of the central retinal artery occlusion and that of the nearly concomitant stroke in the right medial cerebral artery territory was confirmed by bone marrow biopsy to be polycythemia vera (positive JAK2 mutation). Patient received treatment with aspirin, serial phlebotomies, and hydroxyurea, demonstrating a slight improvement in vision and substantial normalization of neurologic and hematological status. At the time of this report, 2 years later, patient remains stable.
Central retinal artery occlusion, a disease with a frequently devastating visual outcome, is often not an “isolated” ocular occurrence. In the absence of an obvious local trigger, a thorough work-up is always warranted, especially in younger patients, as the ocular pathology oftentimes may herald severe cerebro-cardiovascular events.
Here is what I found so far:
1.
BMJ Case Rep. 2016 Oct 20;2016. pii: bcr2016216417. doi: 10.1136/bcr-2016-216417.
Central retinal artery occlusion as a presenting manifestation of polycythaemia vera.
Abstract
Jak2 mutation-positive polycythemia vera presenting as central retinal artery occlusion.
Author information
- 1
- Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York.
Abstract
PURPOSE:
METHODS:
RESULTS:
CONCLUSION:
What Is Primary Myelofibrosis (MF)?
Primary myelofibrosis (MF) is a chronic blood cancer in which excessive scar tissue forms in the bone marrow and impairs its ability to produce normal blood cells.
Researchers believe MF may be caused by abnormal blood stem cells in the bone marrow. The abnormal stem cells produce mature cells that grow quickly and take over the bone marrow, causing both fibrosis (scar tissue formation) and chronic inflammation. As a result, it becomes more difficult for the bone marrow to create normal blood cells and blood cell production may move to the spleen (causing enlargement) or to other areas of the body.
Classified as a myeloproliferative neoplasm (MPN), MF can arise on its own or as a progression of polycythemia vera (post-PV-MF) or essential thrombocythemia (post-ET-MF). The manifestations of MF, post-PV-MF and post-ET-MF are virtually identical and treatment is generally the same for all three.
What Causes MF?
No one knows exactly what triggers the start of myelofibrosis or other myeloproliferative neoplasms. In the majority of cases, myelofibrosis is not inherited genetically — you cannot pass the disease on to your children or inherit it from your parents (although some families do demonstrate a clear predisposition).
Recently, researchers have discovered that these diseases may be caused by acquired gene mutations (changes in DNA that not inherited). Some of these mutations affect proteins that work in signaling pathways in your cells.
Risk factors associated with MF include:
Age
Myelofibrosis is most often diagnosed in people over the age of 60, although there are known cases of myelofibrosis in the young.
Myelofibrosis is most often diagnosed in people over the age of 60, although there are known cases of myelofibrosis in the young.
JAK2 Mutation
Approximately 50% to 60% of people with MF have a mutation of the JAK2 gene within their blood-forming cells. Mutant JAK2 tells blood cells to grow and divide even when the body is not asking for more blood cells. Between 5 and 10% of patients will have a mutation in another gene named MPL, which also affects the JAK signaling pathway.
Approximately 50% to 60% of people with MF have a mutation of the JAK2 gene within their blood-forming cells. Mutant JAK2 tells blood cells to grow and divide even when the body is not asking for more blood cells. Between 5 and 10% of patients will have a mutation in another gene named MPL, which also affects the JAK signaling pathway.
CALR
About 23.5% of people with myelofibrosis and essential thrombocythemia have a mutation called Calreticulin, or CALR. This genetic marker was discovered in 2013 by two independent laboratories, including one funded by the MPN Research Foundation. Research is still ongoing, but there are potential implications for treatments and prognosis for those with the CALR mutation.
About 23.5% of people with myelofibrosis and essential thrombocythemia have a mutation called Calreticulin, or CALR. This genetic marker was discovered in 2013 by two independent laboratories, including one funded by the MPN Research Foundation. Research is still ongoing, but there are potential implications for treatments and prognosis for those with the CALR mutation.
How is MF Diagnosed?
Physicians review a wide range of factors before making a diagnosis of myelofibrosis. Since every case of MF is different, a medical history, a physical examination, laboratory tests and a bone marrow examination are usually required to diagnose the disease.
Even though some people living with myelofibrosis may not have symptoms (things you feel), they frequently exhibit signs (things a doctor notices during a physical examination).
Common signs of MF during physical examinations may include:
- An enlarged spleen (splenomegaly)
- Pale mucous membranes (pallor), if anemia is present
- Loss of muscle mass
- Cachexia (wasting syndrome characterized by weight loss, muscle atrophy, weakness and fatigue)
Common lab tests to diagnose MF include:
Blood Tests
A complete blood count (CBC) often shows abnormal blood cell counts. Red blood cells (erythrocytes), white blood cells (leukocytes), platelets (thrombocytes) or other blood cell types are commonly affected by MF, and counts may be either too high or too low.
A complete blood count (CBC) often shows abnormal blood cell counts. Red blood cells (erythrocytes), white blood cells (leukocytes), platelets (thrombocytes) or other blood cell types are commonly affected by MF, and counts may be either too high or too low.
Bone Marrow Biopsy
An examination of bone marrow under a microscope may reveal that suggest MF, including scar tissue formation and the atypical appearance of bone marrow precursors.
An examination of bone marrow under a microscope may reveal that suggest MF, including scar tissue formation and the atypical appearance of bone marrow precursors.
Gene Mutation Analysis of Blood Cells
Specific mutations associated with some cases of MF (e.g., JAK2, CALR, and MPL) can be identified through gene mutation analysis.
Specific mutations associated with some cases of MF (e.g., JAK2, CALR, and MPL) can be identified through gene mutation analysis.
Imaging Tests
An ultrasound of the spleen or other tests may be done to determine whether the spleen is enlarged.
An ultrasound of the spleen or other tests may be done to determine whether the spleen is enlarged.
What are the Symptoms of MF?
Myelofibrosis symptoms are often caused by an enlarged spleen and/or insufficient numbers of normal blood cells and chronic inflammation.
Common MF symptoms and signs may include:
- Tiredness, weakness, or shortness of breath with mild exertion
- Fullness, discomfort or pain in the left upper area of the abdomen
- Fever
- Night sweats
- Weight loss or malnutrition
- Bone pain
- Itching (pruritus)
- Easy bleeding or bruising
- Susceptibility to infection
- Joint pain or gout
- Abdominal distension/fluid retention (if portal hypertension or increased blood pressure within the portal vein is present)
- Compromised liver function
- Abnormal growth of blood forming cells outside of the bone marrow
Routine medical examinations including complete blood counts (CBCs) are important for diagnosing MF and other MPNs, since some MF patients exhibit no symptoms (especially during the early course of the disease).
What is the Prognosis for MF?
There is no single prognosis for people who suffer from myelofibrosis– the prognosis of MF is different for every patient. While some individuals live for many years without developing major symptoms, others find that the disease progresses more quickly.
Factors that can influence an MF prognosis are age, white blood cell counts, number of “blasts” (immature blood cells) in the blood, “constitutional symptoms” (e.g., night sweats, weight loss, fever), anemia (low red blood cells), transfusion dependence, low platelets and abnormal chromosome analysis.
For most patients, an MF prognosis requires the management of several symptoms and signs, including:
- Anemia (not enough red blood cells to carry oxygen)
- Splenomegaly (enlarged spleen)
- Extramedullary hematopoiesis (production of blood cells in organs outside the bone marrow, such as the spleen and liver)
- Thrombosis and thrombohemorrhagic complications (blood clotting or bleeding complications)
- Leukocytosis (too many white blood cells)
- Thrombocytosis (too many platelets) or thrombocytopenia (low platelet counts)
- Constitutional and systemic (“whole body”) symptoms (e.g., fatigue, night sweats, weight loss, pruritus, fever, bone and joint pain)
- Gout
For a small number of patients, MF can transform to acute myeloid leukemia (AML), a serious blood and bone marrow cancer. When AML does arise from MF, it progresses quickly and can be difficult to treat.
What Are the Available Treatments for MF?
There is no single treatment that is effective for all MF sufferers. Each patient has a unique set of symptoms and circumstances that require different treatment options, as prescribed by a doctor. Also, some patients with MF remain symptom-free for many years and may not require immediate treatment. However, anyone who has been diagnosed with MF needs to be monitored over time for signs or symptoms that suggest the disease has worsened.
Available treatments and therapies for MF include:
Jakafi
Jakafi (ruloxitinib) is the first drug approved by the FDA for treating MF patients. Jakafi is indicated for treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MFAs a targeted therapy, Jakafi is designed to be more specific for abnormal cells. Taken orally, Jakafi partially inhibits the activity of JAK2 and the related protein JAK1. During clinical trials, it was shown to reduce spleen size, abdominal discomfort, early satiety, bone pain, night sweats and itching in MF patients as well as the level of “pro-inflammatory cytokines” in the blood, which may cause some symptoms such as fatigue, fever, night sweats and weight loss. Patients are observed for low blood counts, headache, dizziness, bruising or infection. For more about Jakafi, click here (will be directed to the manufacturer’s website).
Jakafi (ruloxitinib) is the first drug approved by the FDA for treating MF patients. Jakafi is indicated for treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MFAs a targeted therapy, Jakafi is designed to be more specific for abnormal cells. Taken orally, Jakafi partially inhibits the activity of JAK2 and the related protein JAK1. During clinical trials, it was shown to reduce spleen size, abdominal discomfort, early satiety, bone pain, night sweats and itching in MF patients as well as the level of “pro-inflammatory cytokines” in the blood, which may cause some symptoms such as fatigue, fever, night sweats and weight loss. Patients are observed for low blood counts, headache, dizziness, bruising or infection. For more about Jakafi, click here (will be directed to the manufacturer’s website).
Allogenic Stem Cell Transplantation (ASCT)
ASCT is the only curative treatment for MF. Patients need to carefully discuss whether or not they may be eligible for such a procedure, given the complexity and possibility for complications. With ASCT, hematopoietic (blood-forming) stem cells are transferred from a donor to the patient, essentially replacing defective stem cells with healthy ones. Before the stem cell infusion, the patient receives chemotherapy and/or radiation therapy to eradicate diseased bone marrow. Since age and the presence of other diseases elevate the risks associated with ASCT, the decision to pursue ASCT should be made in close consultation with your physician.
ASCT is the only curative treatment for MF. Patients need to carefully discuss whether or not they may be eligible for such a procedure, given the complexity and possibility for complications. With ASCT, hematopoietic (blood-forming) stem cells are transferred from a donor to the patient, essentially replacing defective stem cells with healthy ones. Before the stem cell infusion, the patient receives chemotherapy and/or radiation therapy to eradicate diseased bone marrow. Since age and the presence of other diseases elevate the risks associated with ASCT, the decision to pursue ASCT should be made in close consultation with your physician.
Symptom-Specific Treatments
In many cases, therapies for MF patients target specific signs. These signs and related treatments can include:
- Anemia may be treated with corticosteroids, androgens (including danazol and halotestin), thalidomide, lenalidomide, blood transfusions, or erythropoiesis stimulating agents (ESAs). There are also some drugs currently in clinical trial that aim to improve anemia for people with myelofibrosis.
- Splenomegaly may be treated with Jakafi, hydroxyurea (HU), cladibrine, interferon, or, in severe cases when drug therapy has failed, radiation or splenectomy.
- Risk of thrombosis may be managed with low-dose aspirin therapy or hydroxyurea.
- Non-liver and spleen extramedullary hematopoiesis may be treated with radiation therapy.
- Constitutional symptoms, such as night sweats, pruritus, weight loss and fever may be treated with Jakafi.
Novel Approaches and Clinical Trials
For many patients with MF, available treatment approaches may not be effective, and experimental treatments (which involve receiving a novel drug or treatment on a clinical trial), may be an appropriate option.
So far, only Jakafi (ruxolitinib) has been FDA approved for MF therapy. But other novel therapies are currently in clinical trial, including multiple mechanisms of action:
JAK Inhibitors
A number of other drugs that inhibit JAK2 (“JAK inhibitors”) are currently in clinical trials, including momelotinib, pacrtinib and NS-018. The results of these studies will determine whether these drugs may also be effective for treating MF patients.
A number of other drugs that inhibit JAK2 (“JAK inhibitors”) are currently in clinical trials, including momelotinib, pacrtinib and NS-018. The results of these studies will determine whether these drugs may also be effective for treating MF patients.
Epigenetic Drugs
Epigenetic drugs change the way genes are organized to make them more or less accessible for use by the cell. Recent studies with epigenetic drugs have found that the HDAC inhibitor, Givinostat, and two hypomethylating agents, azacitidine and decitabine, were minimally effective in treating MF in early studies (in contrast to their effectiveness in treating PV). Another HDAC inhibitor, panobinostat, is under study.
Epigenetic drugs change the way genes are organized to make them more or less accessible for use by the cell. Recent studies with epigenetic drugs have found that the HDAC inhibitor, Givinostat, and two hypomethylating agents, azacitidine and decitabine, were minimally effective in treating MF in early studies (in contrast to their effectiveness in treating PV). Another HDAC inhibitor, panobinostat, is under study.
Pomalidomide
Pomalidomide has been shown to effectively treat anemia in early studies. It targets the patient’s immune system to attack abnormal cells in order to make room for the normal cells that make red blood cells. With enhanced anti-cancer activity and lower toxicity compared to the other drugs in its class, pomalidomide has shown promise in initial studies and is now in phase 3 clinical trials for its use as first line therapeutic for treating anemia in MF patients who have the V617F mutation.
Pomalidomide has been shown to effectively treat anemia in early studies. It targets the patient’s immune system to attack abnormal cells in order to make room for the normal cells that make red blood cells. With enhanced anti-cancer activity and lower toxicity compared to the other drugs in its class, pomalidomide has shown promise in initial studies and is now in phase 3 clinical trials for its use as first line therapeutic for treating anemia in MF patients who have the V617F mutation.
Everolimus
Everolimus (also known as RAD001) is an inhibitor of the mTOR/AKT pathway, which is highly active in MF blood producing cells and appears to contribute to abnormal cell growth. In phase 1 and 2 clinical trials, Everolimus was well tolerated and able to reduce both spleen size and systemic symptoms.
Everolimus (also known as RAD001) is an inhibitor of the mTOR/AKT pathway, which is highly active in MF blood producing cells and appears to contribute to abnormal cell growth. In phase 1 and 2 clinical trials, Everolimus was well tolerated and able to reduce both spleen size and systemic symptoms.
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J Am Optom Assoc. 1997 Nov;68(11):734-8.
Retinopathy secondary to anemia from myeloid metaplasia in polycythemia vera.
Abstract
BACKGROUND:
CASE REPORT:
CONCLUSION:
Here is the whole list of Search Words: Polycythemia Vera:
Search results
Items: 23
Myelofibrosis
From Wikipedia, the free encyclopedia
| Myelofibrosis | |
|---|---|
| Classification and external resources | |
| Specialty | Oncology and Hematology |
| ICD–10 | C94.4, D47.4 |
| ICD–9-CM | 289.83 |
| ICD-O | 9931/3, M9961/3 |
| OMIM | 254450 |
| DiseasesDB | 8616 |
| MedlinePlus | 000531 |
| Patient UK | Myelofibrosis |
| MeSH | D055728 |
Myelofibrosis, also known as osteomyelofibrosis, is a relatively rare bone marrow cancer.[1] It is currently classified as a myeloproliferative neoplasm, in which the proliferation of an abnormal clone of hematopoietic stem cells in the bone marrow and other sites results in fibrosis, or the replacement of the marrow with scar tissue.[2][3]
The term myelofibrosis alone usually refers to primary myelofibrosis (PMF), also known as chronic idiopathic myelofibrosis (cIMF); the terms idiopathic and primary mean that in these cases the disease is of unknown or spontaneous origin. This is in contrast with myelofibrosis that develops secondary to polycythemia vera or essential thrombocythaemia. Myelofibrosis is a form of myeloid metaplasia, which refers to a change in cell type in the blood-forming tissue of the bone marrow, and often the two terms are used synonymously. The terms agnogenic myeloid metaplasia and myelofibrosis with myeloid metaplasia (MMM) are also used to refer to primary myelofibrosis.
Contents
[hide]
Signs and symptoms[edit]
The primary sign of myelofibrosis is reactive bone marrow fibrosis,[3] but it is often accompanied by:
- Abdominal fullness related to an enlarged spleen (splenomegaly).
- Bone pain
- Bruising and easy bleeding due to inadequate numbers of platelets
- Cachexia (loss of appetite, weight loss, and fatigue)
- Enlargement of both the liver and spleen
- Fatigue
- Gout and high uric acid levels
- Increased susceptibility to infection, such as pneumonia
- Pallor and shortness of breath due to anemia
- In rarer cases, a raised red blood cell volume
- Cutaneous myelofibrosis is a rare skin condition characterized by dermal and subcutaneous nodules.[4]:746
Causes[edit]
There is an association between mutations to the JAK2, CALR, or MPL gene and myelofibrosis.[5] Approximately 90% of those with myelofibrosis have one of these mutations and 10% carry none of these mutations. These mutations are not specific to myelofibrosis, and are linked to other myeloproliferative disorders, specifically polycythemia vera and essential thrombocythemia.[3]
The V617F mutation to the JAK2 protein is found in approximately half of individuals with primary myelofibrosis.[6] The V617F mutation is a change of valine to phenylalanine at the 617 position. Janus kinases (JAKs) are non-receptor tyrosine kinases essential for the activation of signaling that is mediated by cytokine receptors lacking catalytic activity. These include receptors for erythropoietin, thrombopoietin, most interleukins and interferon.[6] JAK2 mutations are significant because JAK2 plays a role in controlling production of blood cells from hematopoietic stem cells. The V617F mutation appears to make hematopoietic cells more sensitive to growth factors that need JAK2 for signal transduction, which include erythropoietin and thrombopoietin.[7]
The MPL gene codes for a protein that acts as a receptor for thrombopoietin. A mutation in that gene, known as a W515 mutation, leads to the production of an abnormal thrombopoietin receptor protein, which results in the overproduction of abnormal megakaryocytes. The abnormal megakaryocytes stimulate other cells, the fibroblasts, to produce collagen in the bone marrow.[8]
Mechanism[edit]
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)[9] 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, ie. blood cell formation occurring in sites other than the bone marrow, as the haemopoetic 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 thrombocythaemia. 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.[10]
The cause and risk factors for primary myelofibrosis are unknown.
Sites of hematopoiesis[edit]
The principal site of extramedullary hematopoiesis in myelofibrosis is the spleen, which is usually markedly enlarged, sometimes weighing as much as 4000 g. As a result of massive enlargement of the spleen, multiple subcapsular infarcts often occur in the spleen, meaning that due to interrupted oxygen supply to the spleen partial or complete tissue death happens. On the cellular level, the spleen contains red blood cell precursors, granulocyte precursors and megakaryocytes, with the megakaryocytes prominent in their number and in their bizarre shapes. Megakaryocytes are believed to be involved in causing the secondary fibrosis seen in this condition, as discussed under “Pathophysiology” above. Sometimes unusual activity of the red blood cells, white blood cells, or platelets is seen.
The liver is often moderately enlarged, with foci of extramedullary hematopoiesis. Microscopically, lymph nodes also contain foci of hematopoiesis, but these are insufficient to cause enlargement.
There are also reports of hematopoiesis taking place in the lungs. These cases are associated with hypertension in the pulmonary arteries.[11]
The bone marrow in a typical case is hypercellular and diffusely fibrotic. Both early and late in disease, megakaryocytes are often prominent and are usually dysplastic.
Diagnosis[edit]
Epidemiologically, the disorder usually develops slowly and is mainly observed in people over the age of 50.[12] It may also develop as a side-effect of treatment with some drugs that target hematological disorders, such as polycythemia vera or chronic myelogenous leukemia. Diagnosis of myelofibrosis is made on the basis of bone marrow biopsy.[3] A physical exam of the abdomen may reveal enlargement of the spleen, the liver, or both.[3]
Blood tests are also used in diagnosis. Primary myelofibrosis can begin with a blood picture similar to that found in polycythemia vera or chronic myelogenous leukemia. Most people with myelofibrosis have moderate to severe anemia. Eventually thrombocytopenia, a decrease of blood platelets develops. When viewed through a microscope, a blood smear will appear markedly abnormal, with presentation of pancytopenia, which is a reduction in the number of all blood cell types: red blood cells, white blood cells, and platelets. Red blood cells may show abnormalities including bizarre shapes, such as teardrop-shaped cells, and nucleated red blood cell precursors may appear in the blood smear. (Normally, mature red blood cells in adults do not have a cell nucleus, and the presence of nucleated red blood cells suggests that immature cells are being released into the bloodstream in response to a very high demand for the bone marrow to produce new red blood cells.) Immature white cells are also seen in blood samples, and basophil counts are increased.
When late in the disease progression an attempt is made to take a sample of bone marrow by aspiration, it may result in a dry tap, meaning that where the needle can normally suck out a sample of semi-liquid bone marrow, it produces no sample because the marrow has been replaced with collagen fibers. A bone marrow biopsy will reveal collagen fibrosis, replacing the marrow that would normally occupy the space.
Treatment[edit]
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The one known curative treatment is allogeneic stem cell transplantation, but this approach involves significant risks.[13] Other treatment options are largely supportive, and do not alter the course of the disorder (with the possible exception of ruxolitinib, as discussed below).[14] These options may include regular folic acid,[15] allopurinol[16] or blood transfusions.[17] Dexamethasone, alpha-interferon and hydroxyurea (also known as hydroxycarbamide) may play a role.[18][19][20]
Lenalidomide and thalidomide may be used in its treatment, though peripheral neuropathy is a common troublesome side-effect.[20]
Frequent blood transfusions may also be required.[17] If the patient is diabetic and is taking a sulfonylurea, this should be stopped periodically to rule out drug-induced thrombocytopenia.[citation needed]
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.[21]
In November 2011, the FDA approved ruxolitinib (Jakafi) as a treatment for intermediate or high-risk myelofibrosis.[22][23] Ruxolitinib serves as an inhibitor of JAK 1 and 2. The New England Journal of Medicine (NEJM) published results from two Phase III studies of ruxolitinib. These data showed that the treatment significantly reduced spleen volume, improved symptoms of myelofibrosis, and was associated with improved overall survival compared to placebo.[24][25]
History[edit]
Older terms include “myelofibrosis with myeloid metaplasia” and “agnogenic myeloid metaplasia”. The World Health Organization utilized the name “chronic idiopathic myelofibrosis”, while the International Working Group on Myelofibrosis Research and Treatment calls the disease “primary myelofibrosis”. In 2008 WHO has adopted the name of “primary myelofibrosis.” Eponyms for the disease are Heuck-Assmann disease or Assmann’s Disease, for Herbert Assmann,[28] who published a description under the term “osteosclerosis” in 1907.[29]
It was characterised as a myeloproliferative condition in 1951 by Dameshek.[30][31] The Leukemia and Lymphoma Society describes myelofibrosis as a rare type of blood cancer, manifesting as a type of chronic leukemia.[32]
References[edit]
- ^ “Myelofibrosis Facts” (PDF). The Leukemia and Lymphoma Society. Retrieved 5 October 2014.
- ^ “myelofibrosis” at Dorland’s Medical Dictionary
- ^ a b c d e Tefferi, Ayalew (2014). “Primary myelofibrosis: 2014 update on diagnosis, risk-stratification, and management”. American Journal of Hematology. 89 (9): 915–925. doi:10.1002/ajh.23703. ISSN 0361-8609.
- ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews’ Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
- ^ Tefferi, A; Lasho, T L; Finke, C M; Knudson, R A; Ketterling, R; Hanson, C H; Maffioli, M; Caramazza, D; Passamonti, F; Pardanani, A (2014). “CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons”. Leukemia. 28 (7): 1472–1477. doi:10.1038/leu.2014.3. ISSN 0887-6924.
- ^ a b Staerk, Judith; Constantinescu, Stefan N. (2014). “The JAK-STAT pathway and hematopoietic stem cells from the JAK2 V617F perspective”. JAK-STAT. 1 (3): 184–190. doi:10.4161/jkst.22071. ISSN 2162-3996.
- ^ Them, Nicole C. C.; Kralovics, Robert (2013). “Genetic Basis of MPN: Beyond JAK2-V617F”. Current Hematologic Malignancy Reports. 8 (4): 299–306. doi:10.1007/s11899-013-0184-z. ISSN 1558-8211.
- ^ Tefferi, A (2010). “Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1”. Leukemia. 24 (6): 1128–1138. doi:10.1038/leu.2010.69. ISSN 0887-6924.
- ^ Chou JM, et al. (2003). “Bone marrow immunohistochemical studies of angiogenic cytokines and their receptors in myelofibrosis with myeloid metaplasia”. Leukemia Research. 27 (6): 499–504. doi:10.1016/S0145-2126(02)00268-0. PMID 12648509.
- ^ Najean Y, Rain JD (1997). “Treatment of polycythemia vera: the use of hydroxyurea and piprobroman in 292 patients under the age of 65 years”. Blood. 90 (9): 3370–7. PMID 9345019.
- ^ Trow, TK; et all (2010). “A 71-Year-Old Woman With Myelofibrosis, Hypoxemia, and Pulmonary Hypertension”. Chest. 138 (6): 1506–10. doi:10.1378/chest.10-0973. PMID 21138888.
- ^ Primary Myelofibrosis, Merck.
- ^ Cervantes F (March 2005). “Modern management of myelofibrosis”. Br. J. Haematol. 128 (5): 583–92. doi:10.1111/j.1365-2141.2004.05301.x. PMID 15725078.
- ^ Kröger N, Mesa RA (March 2008). “Choosing between stem cell therapy and drugs in myelofibrosis”. Leukemia. 22 (3): 474–86. doi:10.1038/sj.leu.2405080. PMID 18185525.
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