FAQ: About Myelofibrosis

  1. What is myelofibrosis?
  2. How is myelofibrosis diagnosed?
  3. What is the value of the bone marrow biopsy and how do I cope with it?
  4. What is the prognosis of myelofibrosis?
  5. How could I have got myelofibrosis?
  6. What are the main treatment options for myelofibrosis?
  7. Making treatment decisions in myelofibrosis.
  8. If I choose one treatment for myelofibrosis, does this influence any later choice, e.g. bone marrow transplant?
  9. Are there any new treatment options coming along?
  10. How often do I need check-ups
  11. What is my life expectancy?
  12. What impact may myelofibrosis and its treatment have on my fertility/menopause?
  13. What impact may there be on sexuality?



1. What is myelofibrosis?
It is a disease of the bone marrow in which the bone marrow becomes fibrotic. This fibrotic scar tissue inside the marrow cavity eventually takes over leading to increasingly inefficient blood cell production and ultimately may result in bone marrow failure. It may be called by several names including primary or idiopathic myelofibrosis (more common in the British health system) or agnogenic myeloid metaplasia (usually used in the USA). These names describe a situation where myelofibrosis is the first disease diagnosed. It is also possible to have myelofibrosis as a consequence of another myeloproliferative diseases such as polycythemia vera (PV), essential thrombocythemia (ET), or chronic myelogenous leukemia.

In the setting of a myeloproliferative disorder, myelofibrosis is accompanied by varying degrees of myeloid metaplasia (often seen as enlargement of spleen and/or liver), due to reactivation of fetal hematopoietic sites than are normally dormant in adult life. It is this combination that distinguishes myeloproliferative disease-related myelofibrosis from the secondary or interactive myelofibrosis that occurs in the setting of malignancy, chemical or physical injury, infection or infarction. The increase of fibrous tissue in the bone marrow, the extramedullary haematopoeisis that presents itself primarily as progressive enlargement of the spleen (splenomegaly), and the leuko-erythroblastosis in the peripheral blood form the basis of the myriad clinical presentations of myelofibrosis. Clinical and laboratory findings, the course and complications and the ultimate outcome are determined by the degree of preservation of normal haematopoeitic tissue, the extent of hematic dysplasia, and the balance between cell proliferation and cell destruction.

2. How is myelofibrosis diagnosed?
Usually by a physician noticing low red cell counts and perhaps other abnormal blood counts such as elevated white cell and/or platelet count during a routine exam or as a result of an examination to determine the cause of a patient's complaints of feeling more tired than usual or that their abdomen is tender and enlarged or bloated (this comes from the enlarged spleen), bruising, etc. An alert doctor will request a full blood screen which will identify that some elements of the blood counts are abnormal and may follow up with an abdominal ultrasound or other scan before sending a patient to a haematologist for further work-up. To be sure of the diagnosis a bone marrow biopsy is required to test the state of the marrow itself and provide conclusive evidence of the disorder.

3. What is the value of the bone marrow biopsy and how do I cope with it?
It is important as it provides a bench mark for measuring the progress of the bone marrow directly. The blood reports show the consequences of the state of the bone marrow. Nothing beats firsthand information. Some doctors claim they can tell by peripheral blood counts and do not rely on bone marrow biopsies. As you can see from the above criteria, it is virtually impossible to stage the disease without this tool. And staging provides a guide to the most appropriate treatment option.

However the procedure may be difficult as local anesthetics cannot reach the bone marrow itself. You may find that if you prepare with a relaxant (mild tranquilizer) about an hour ahead that the procedure (which takes 3 - 30 minutes depending on skill and bone density) can be coped with.

4. What is the prognosis of myelofibrosis?
In general, the survival of patients with idiopathic myelofibrosis seems to a large extent programmed by their presenting findings and is not very much altered by therapy. Approximately 60% of patients with idiopathic myelofibrosis live 5 years. There is a significant cohort of patients who live 10 years or more. Patients with idiopathic myelofibrosis who tend to do very well include those whose presenting hemoglobin levels are greater than 10 gm/dl, platelet counts greater than 100x3/ul and only modest enlargement of the liver. Spleen size and sex seem to have no prognostic significance.

5. How could I have got myelofibrosis?
If you were previously diagnosed with a myeloproliferative disorder (MPD) such as essential thrombocythemia, polycythemia vera or chronic myelogenous leukemia, your myelofibrosis is reactive and secondary to the pre-existing MPD. If it arose de novo with no prior history of another MPD, no one knows for sure. You might have had a prior undiagnosed myeloproliferative disorder, discovered only after you developed myelofibrosis. It might be likely to be a specific gene abnormality which develops over a period of years.

6. What are the main treatment options for myelofibrosis?
For asymptomatic patients, no treatment is necessary.

The profound anemia that develops in this disease usually requires red blood cell transfusion. Red blood cell survival is markedly decreased in some patients; this can sometimes be treated with glucocorticoids. Disease-associated anemia may occasionally respond to erythropoietin, hydroxyurea, cladribine, thalidomide, or interferon.

Hydroxyurea is useful in patients with this disease but may have a potential leukemogenic effect (initiation or pregression of leukemic disease). In patients with thrombocytosis and abnormal enlargement of the liver after surgical removal of the spleen, cladribine has shown responses as an alternative to hydroxyurea. The use of interferon alfa can result in hematologic responses, including reduction in spleen size in 30% to 50% of patients, though many patients do not tolerate this medication. Favorable responses to thalidomide have been reported in about 20% to 60% of patients. Another approach involves allogeneic peripheral stem cell, umbilical stem cell or bone marrow transplantation when a suitable sibling donor is available.

Painful abnormal enlargement of the spleen can be treated temporarily with chemotherapy (hydroxyurea), interferon, or radiation therapy, but often requires the surgical removing of the spleen (splenectomy).

The decision to perform splenectomy represents a weighing of the benefits (i.e., reduction of symptoms, decreased portal hypertension, and less need for red blood cell transfusions) versus the debits (i.e., risk of postoperative deaths of 10% and illness of 30% caused by infection, bleeding, or thrombosis).

7. Making treatment decisions in myelofibrosis.
Why is a particular treatment recommended? How important are social and psychological factors in choosing a treatment option? As you can see from the above discussion, there isn't a single myelofibrosis with a given set of symptoms and conditions which respond to a specific treatment. If a patient's marrow is still overproducing platelets, red cells and white cells, their treatment needs are completely different from a patient whose marrow is barely functioning.

Each patient needs to work with his or her doctor in deciding on the best treatment option. Only your doctor has reviewed your records and test results and can recommend a specific course of action that has the best chance of dealing with your condition. The important thing from the patient standpoint is to understand what treatment options are available and discuss what is best for you with your hematologist.

Coming to the understanding that these are chronic, incurable (without a successful bone marrow/stem cell transplant) conditions that require medical monitoring and treatment for the remainder of one's life can be difficult and we all cope in different ways. Some patients feel that quality of life issues are the most important consideration. There are several women in our group who were quite upset by hair loss, fatigue and lack of response in shrinking their spleen and opted for splenectomy so they could stop the interferon. Some do not have insurance that covers the cost of a particularly treatment. In countries with a national health care system, for example, interferon may not be available as a treatment option unless the patient pays for it personally. In the United States, Medicare patients face difficult economic issues if interferon is the drug of choice.

Living with a potentially life-threatening chronic disease is difficult. You will need to learn how to chill out so to speak. This is not like a broken leg or similar physical injury. It is a chronic disease which will require you to make certain changes in your life from now on; for ever more. Unless you have a successful bone marrow/stem cell transplant; which is not considered standard care at the moment; you will live with this for the rest of your life. And your life will be different.

8. If I choose one treatment for myelofibrosis, does this influence any later choice, e.g. bone marrow transplant?
It is not known for sure but it seems highly possible that the choice you make about treatment may influence your system's capacity to deal with subsequent choices. Prolonged chemotherapy damages organs and patients may be less able to weather the severe or reduced intensity conditioning (RIC) chemotherapy required prior to a bone marrow transplant.

However, since some do well for a period of years with no treatment and some have seen improvement or reversal on interferon, this presents difficult choices if one is young enough for a transplant and has a matched related donor.

9. Are there any new treatment options coming along?
There is a huge amount of material available on the Internet about treatments and case reports. But as myeloproliferate diseases are rare, there is not much research specifically focussing at these diseases. For this reason an international research Consortium named the MPD-RC has been created. The MPD-RC is an international, multi-institutional no profit consortium set up to coordinate, facilitate, and perform basic and clinical research investigating the genetic and cellular mechanisms of the Philadelphia Chromosome (Ph) negative myeloproliferative disorders (MPD). The ultimate goal is to develop novel therapeutic strategies to improve the management of patients with this type of diseases. This program is led by Dr. Ronald Hoffman, a nationally and internationally recognized investigator who has brought together highly qualified and experienced investigators, and efficiently established a complex, well assembled, highly synergistic and innovative structure.

10. How often do I need check-ups
Different doctors will have different expectations - but you should expect monthly checks in the early stages while the doctor or team determines whether you are in a stable or deteriorating state; followed by two or three monthly checks if you are early and stable.

11. What is my life expectancy?
The only answer is that no one knows for sure. It may be as little as three years (less with the acute form) but it may be 10 - 15 years - or who knows it may be the full span if you have a successful bone marrow/stem cell transplant.

12. What impact may myelofibrosis and its treatment have on my fertility/menopause?
This is an issue you need to discuss with your doctor. But if you have a bone marrow/stem cell transplant, you can expect instant menopause.

13. What impact may there be on sexuality?
When one is faced with a diagnosis of a life threatening disease this has a real impact on both the individual and the relationship they are in. Our sense of ourselves as a whole healthy person is challenged and we are forced to face mortality. Over time our body does not work as well as before and we may become very focused on the disease as it assumes a greater portion of our lives. The increased anxiety as well as effects of medication all impact on one's sexuality.

The reality is that things are not going to be what they were before. The challenge is to find positive ways to maintain and enhance the physical and emotional benefits that accrue from the expression of our sexuality.