myelofibrosis

Myelofibrosis 

Definition

Myelofibrosis is a rare disease of the bone marrow in which collagen builds up fibrous scar tissue inside the marrow cavity. This is caused by the uncontrolled growth of a blood cell precursor, which results in the accumulation of scar tissue in bone marrow. Myelofibrosis goes by many names including idiopathic myelofibrosis, agnogenic myeloid metaplasia, chronic myelosclerosis, aleukemic megakaryocytic myelosis, and leukoerythroblastosis.

Description

Myelofibrosis can be associated with many other conditions including breast cancer, prostate cancer, Hodgkin's disease, non-Hodgkin's lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, hairy cell leukemia, multiple myeloma, myeloproliferative diseases, tuberculosis, Gaucher's disease, and Paget's disease of bone. Myelofibrosis typically becomes progressively worse and can cause death.

In myelofibrosis, abnormal cells (hematopoietic stem cells) grow out of control and begin to produce both immature blood cells and excess scar (fibrous) tissue. The fibrous tissue builds up (fibrosis) primarily in the bone marrow, the place where blood cells are produced. The fibrous tissue interferes with the production of normal blood cells. The outcome of this is that the blood made by the bone marrow is of poor quality. To compensate for this, blood cell production occurs in other parts of the body (extramedullary hematopoiesis), but most notably in the spleen and liver. This causes enlargement of the spleen (splenomegaly) and the liver (hepatomegaly). Extramedullary hematopoiesis is not effective and, combined with the reduced production of blood cells by the bone marrow, a condition called anemia results.

The abnormal stem cells can spread throughout the body, settle in other organs, and form tumors that produce more abnormal blood cells and fibrous tissue. These tumors are most commonly found in the adrenals, kidneys, lymph nodes, breast, lungs, skin, bowel, thymus, thyroid, prostate, and urinary tract.

Most patients with myelofibrosis are over 50 years old; the average age at diagnosis is 65 years. However, myelofibrosis can occur at any age. Myelofibrosis occurs with equal frequency in women and men, but in children it affects girls twice as often as it does boys.

Causes and symptoms

Myelofibrosis is caused by an abnormality in a single stem cell, which causes it to grow out of control. Myelofibrosis tumors that have originated from a single cell are called monoclonal. The cause of the stem cell abnormality is unknown. Persons who were exposed to benzene or high doses of radiation have developed myelofibrosis. There may be an association between myelofibrosis and autoimmune diseases, such as systemic lupus erythematosus and scleroderma, in which the immune system treats certain molecules of the body as foreign invaders.

Symptoms usually appear slowly over a long period of time. About one quarter of all patients with myelofibrosis have no symptoms (asymptomatic). An enlarged spleen discovered at an annual medical examination may be the first clue. Symptoms of myelofibrosis include:

• fatigue
• weight loss
• paleness
• fever
• sweating
• weakness
• heart palpitations
• shortness of breath
• itchiness
• feeling full after eating a small amount of food
• stomach pain or discomfort
• pain in the left shoulder or upper left portion of the body
• unexpected bleeding
• bone pain, especially in the legs

Diagnosis

Because symptoms are similar to other diseases (mostly leukemias), myelofibrosis is not easy to diagnose. The doctor would use his or her hands to feel (palpate) for enlargement of the spleen and liver. Blood tests and urine tests would be performed. Bone marrow aspiration and biopsy can help make a diagnosis, but they often fail because of the fibrosis. X-ray imaging and magnetic resonance imaging (MRI) may be performed.

Treatment

Many asymptomatic patients, if stable, do not require treatment. There is no cure for myelofibrosis, although bone marrow transplantation is curative in some cases. Treatment is aimed at reducing symptoms and improving quality of life.

Medications

Male hormones (androgens) can be used to treat anemia but, in women, these drugs can cause the development of male characteristics (e.g., hair growth on the face and body). Glucocorticoid therapy is also an effective treatment of anemia and can improve myelofibrosis in children. Nutrients that stimulate blood formation (hematinics), such as iron, folic acid, and vitamin B₁₂, may reduce anemia. Cancer chemotherapy (usually hydroxyurea) can decrease splenomegaly and hepatomegaly, reduce symptoms of myelofibrosis, lessen anemia, and sometimes reduce bone marrow fibrosis. The bone marrow of myelofibrosis patients is often not strong enough to withstand the harsh chemotherapy drugs, so this treatment is not always an option. Interferonalpha has been shown to reduce spleen size, reduce bone pain, and, in some cases, increase the number of blood platelets (structures involved in blood clotting).

Other treatments

In certain cases, the enlarged spleen may be removed (splenectomy). Conditions that warrant splenectomy include spleen pain, the need for frequent blood transfusion, very low levels of platelets (thrombocytopenia), and extreme pressure in the blood vessels of the liver (portal hypertension).

Radiation therapy is used to treat splenomegaly, spleen pain, bone pain, tumors in certain places such as next to the spinal cord, and fluid accumulation inside the abdomen (ascites). Patients who are not strong enough to undergo splenectomy are often treated with radiation therapy.

Bone marrow transplantation may be used to treat some patients with myelofibrosis. This procedure may be performed on patients who are less than 50 years old, have a poor life expectancy, and have a brother or sister with blood-type similarities.

Patients with severe anemia may require blood transfusions.

Prognosis

Similar to leukemias, myelofibrosis is progressive and often requires therapy to control the disease. Myelofibrosis can progress to acute lymphocytic leukemia or lymphoma. Although a number of factors to predict the survival time have been proposed, advanced age or severe anemia are consistently associated with a poor prognosis. The average survival rate of patients diagnosed with myelofibrosis is five years. Death is usually caused by infection, bleeding, complications of splenectomy, heart failure, or progression to leukemia. Spontaneous remission is rare.

Key terms

Anemia — Low numbers of red blood cells in the blood.

Benzene — A colorless volatile flammable toxic liquid hydrocarbon used as a solvent and as a motor fuel.

Biopsy — Surgical removal of tissue for microscopic examination.

Fibrosis — Buildup of scar tissue.

Glucocorticoid therapy — Treatment using corticoids that are anti-inflammatory and immunosuppressive.

Leukemia — Cancer of white blood cells.

Portal hypertension — Extreme pressure on the blood vessels of the liver.

Stem cell — A cell that has the ability to become many different specialized cells.

Prevention

Persons who have been exposed to radiation, benzene, or radioactive thorium dioxide (a chemical used during certain diagnostic radiological procedures) are at risk for myelofibrosis.

Resources

Books

Lichtman, Marshall. "Idiopathic Myelofibrosis (Agnogenic Myeloid Metaplasia)." In Williams Hematology, edited by Ernest Beutler, et al. New York: McGraw Hill, 2001, pp.1125-36.

Mavroudis, Dimitrios and John Barrett. "Myelofibrosis (Agnogenic Myeloid Metaplasia)." In Bone Marrow Failure Syndromes, edited by Neal Young. Philadelphia: W.B. Saunders Company, 2000, pp.122-34.

Peterson, Powers. "Myelofibrosis." In Practical Diagnosis of Hematologic Disorders, edited by Carl Kjeldsberg. Chicago: ASCP Press, 2000, pp.477-9.

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myelofibrosis /my·elo·fi·bro·sis/ (-fi-bro´sis) replacement of bone marrow by fibrous tissue.

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my·e·lo·fi·bro·sis (m-l-f-brss)

n.

Fibrosis of the bone marrow associated with myeloid metaplasia, leukoerythroblastosis, and thrombocytopenia. Also called myelosclerosis.

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myelofibrosis

[mī′əlōfībrō′sis]

the replacement of bone marrow with fibrous tissue. The condition may be associated with anemia, thrombocytopenia, myeloid metaplasia, new bone formation, polycythemia vera, and other abnormalities. Also called myelosclerosis. See also myeloid metaplasia.

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myelofibrosis

replacement of bone marrow by fibrous tissue, e.g. in the end-stage of myeloid metaplasia and myelofibrosis.

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myelofibrosis

Agnogenic myelofibrosis, agnogenic myeloid metaplasia, marrow fibrosis, myelofibrosis with myeloid metaplasia, idiopathic myelofibrosis, myeloid metaplasia, myelosclerosis, primary myelofibrosis Hematology A chronic progressive condition—panmyelosis characterized by variable fibrosis of BM, massive splenomegaly 2º to extramedullary hematopoiesis and leukoerythroblastic anemia with dysmorphic RBCs, circulating normoblasts, immature WBCs, atypical platelets Clinical Often > age 50; insidious weight loss, anemia, abdominal discomfort due to splenomegaly, often hepatomegaly; 80% have nonspecific chromosome defects Bone marrow Megakaryocytic hyperplasia, ↑ reticulin fibers, giant cells and immature forms, virus-like particles, granulocytic and erythrocytic hyperplasia, chromosomal abnormalities–eg, of 21q which may correlate with reverse transcriptase activity Lab Thrombocytosis–1-14 x 1012/L with giant and bizarre forms, hypochromic and microcytic anemia or erythrocytosis, elliptocytosis, Howell-Jolly bodies, target cells, teardrop cells; leukocytosis–15-40 x 1012/L with ↑ 'bands', ie left shift of granulocytes, juvenile metamyelocytes, ± eosinophilia, basophilia, splenic atrophy, ↑ leukocyte alk phos, platelet acid phosphatase, uric acid, vitamin B₁₂, low-grade DIC Diagnosis BM Bx Management AMM has no specific therapy; packed RBCs for anemia, androgens may ↓ the transfusion requirements in some Pts, but are poorly tolerated in ♀; recombinant erythropoietin Prognosis Survival ± 5 yrs, often → acute leukemia. See Idiopathic onychomycosis, Pseudonym syndrome.

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Patient discussion about myelofibrosis.

Q. Are there any specific treatments for acute myeloid leukemia caused by myelofibrosis? My husband was diagnosed with these conditions. His oncologist believes his AML was caused by his myelofibrosis. (scarring of the bone marrow) This was shown on his bone marrow biopsy. Myelofibrosis is a myeloproliferative disorder. Meaning certain blood components, such as WBCs, RBCs, platelets increase significantly in the marrow.

A. Thanks for taking the time to reply to me. I'll see about inquiring his oncologists.
Lynda