Myelofibrosis is a disorder of the bone marrow that contains the stem cells that will form the red and white blood cells. In myelofibrosis, the bone marrow is replaced by fibrous (scar) tissue. When the bone marrow is scarred, it cannot make enough blood cells. This leads to anemia, weakness, fatigue, increased susceptibility to infections, and often, swelling of the liver and spleen.
Because blood cell formation (hematopoiesis) in the bone marrow is disrupted, other organs such as the spleen or liver may begin to produce blood cells (“myeloid metaplasia”). This process, called extramedullary hematopoiesis, often leads to an enlarged spleen (splenomegaly) or an enlarged liver (hepatomegaly). People with splenomegaly may feel pain or fullness in the abdomen, especially below the ribs on the left side. Other common signs and symptoms of primary myelofibrosis include fever, night sweats, and bone pain.
Although myelofibrosis can occur at any age, it typically develops after the age of 50 years. In most cases, myelofibrosis gets progressively worse. Primary myelofibrosis is a rare condition that affects approximately 1 in 500,000 people worldwide.
The disorder occurs when blood stem cells develop somatic mutations in the JAK2, MPL, CALR, and TET2 genes. Other genes may also be involved. The disorder is generally not inherited because this type of mutation does not affect the reproductive cells (sperm and egg) only certain cells of the body (somatic).
The JAK2 and MPL genes provide instructions for making proteins that promote the growth and division (proliferation) of blood cells. The CALR gene provides instructions for making a protein with multiple functions, including ensuring the proper folding of newly formed proteins and maintaining the correct levels of stored calcium in cells. The TET2 gene provides instructions for making a protein whose function is unknown.
The proteins produced from the JAK2 and MPL genes are both part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell's nucleus. The protein produced from the MPL gene, called thrombopoietin receptor, turns on (activates) the pathway, and the JAK2 protein transmits signals after activation. Through the JAK/STAT pathway, these two proteins promote the proliferation of blood cells, particularly a type of blood cell known as a megakaryocyte.
Mutations in either the JAK2 gene or the MPL gene that are associated with primary myelofibrosis lead to overactivation of the JAK/STAT pathway. The abnormal activation of JAK/STAT signaling leads to overproduction of abnormal megakaryocytes, and these megakaryocytes stimulate another type of cell to release collagen. Collagen is a protein that normally provides structural support for the cells in the bone marrow. However, in primary myelofibrosis, the excess collagen forms scar tissue in the bone marrow.
Although mutations in the CALR gene and the TET2 gene are relatively common in primary myelofibrosis, it is unclear how these mutations are involved in the development of the condition.
Some people with primary myelofibrosis do not have a mutation in any of the known genes associated with this condition. Researchers are working to identify other genes that may be involved in the condition.
Treatment is aimed at relieving signs and symptoms and may include medications, blood transfusions, chemotherapy, radiation therapy, and surgery. Bone marrow or stem cell transplant may improve symptoms and may cure the disease. Ruxolitinib Phosphate (Brand name: Jakafi), manufactured by Incyte Corporation, is an FDA-approved treatment for patients with intermediate or high-risk myelofibrosis.
Reduced-intensity stem cell transplant (Mini-SCT)
An alternative option for older individuals that may not be able to tolerate the intensive pre-treatment with radiation and chemotherapy that a conventional SCT requires, is what has been called a "mini"-SCT. Mini-transplant patients are pre-treated with lower doses of chemotherapy, generally without radiation therapy, which they tolerate better. They then receive an infusion of donor stem cells from a compatible donor, which reconstitute the bone marrow with healthy stem cells that give rise to normal red blood cells, white blood cells, and platelets.
Mini-SCT has been successfully used to treat aplastic anemia, leukemia, myelodysplasia, myeloproliferative diseases, lymphoma, and multiple myeloma. Unlike conventional SCT, which essentially eliminates all lthe stem cells in the bone marrow, mini-SCT suppresses the bone marrow to allow healthy donor stem cells to reconstitute the bone marrow.
While there are still significant risks with the mini-SCT, it is an option for older patients that may not tolerate conventional bone marrow therapy.
Disability Benefits for Myelofibrosis
Whether you are eligible for long-term disability benefits under the Social Security Act (SSDI) and/or in accordance with an employer-based disability plan (ERISA), will depend on the stage of your myelofibrosis, the symptoms and functional limitations that you have, and the adequacy of the medical documentation in your medical record.
If you have myelofibrosis and suffer from chronic anemia, with a hemoglobin level <10, and have tiredness, severe fatigue, weakness, light-headedness, and other related symptoms, your functional capacity may be "less than sedentary" (meaning you are unable to perform even a "desk job"), and your chances of a long-term disability benefit award should be favorable. If you are prone to repeated infections, by virtue of a low white blood cell count, then certain working environments (crowds, multiple-person offices) may be medically contraindicated, because of the risk of exposure to infection. If you require treatment with immunosupressive drugs or chemotherapy, side effects from those drugs may also restrict your ability to work.