It is a disease of the bone marrow in which collagen builds up fibrous scar tissue inside the marrow cavity. The trigger for its development is a disturbance of the immune system. It may be called by several names including primary or ideopathic 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) or essential thrombocythemia (ET).
The outcome is that the blood made by the marrow is of poor quality. The red blood cells are tear drop shaped, large and sluggish and the white blood cells are overabundant. This poor quality blood triggers a response from the spleen and liver as they try to compensate including creating blood themselves (usually only done by the foetus). If left untreated the person eventually will have marrow failure which leads to death. How is the diagnosis made?
Commonly the patient will attend a doctor about something else and may mention that they feel more tired than usual or that their abdomen in tender and enlarged or bloated (this comes from the enlarged spleen). An alert doctor will request a full blood screen which will identify that some elements of the blood counts are abnormal.
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. As well, an enlarged spleen and/or liver is also evidence of a myeloproliferative disorder.
Back To Top
Should I get a second opinion?
There is probably not a lot to be gained from a second opinion with regard to diagnosis. However some hematologists will have had more experience at dealing with the disease; others use a wide range of tools and others will provide a positive framework for your questions. So don't necessarily accept the first opinion as being the best.
Back To Top
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.
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 about an hour ahead that the procedure (which takes 3 - 5 minutes depending on skill and bone density) can be coped with. A skilled technician or nurse who does the procedure on a regular basis is preferable to a doctor who does it rarely. Some physician's will order intravenous medication such as a combination of demerol and versed or morphine and valium. Others require a general anesthetic (which has its own risks and takes longer to recover from). If you find it difficult, insist on pain relief. You will need to have these about twice a year so you have to find a way to cope with them that suits you.
Back To Top
What are the stages of the disease?
This is a portion taken from a textbook: Hematologic Diseases, Agnogenic Myeloid Metaplasia.
"Some observers have felt that the disease can be divided into acute and chronic forms, patients with the chronic form having a median survival of about 10 years. An extremely aggressive form of myelofibrosis has been identified. One patient that has been reported presented with infection and anemia. Bone marrow aspirate showed increased cellularity. Two months later, it was impossible to obtain bone marrow aspirates; biopsy showed findings characteristic of AMM. The peripheral blood contained large numbers of myeloblasts and the anemia became severe. There was no hepato-splenomegaly. The patient died 11 months after the anemia was identified. Postmortem examination demonstrated extramedullary hematopoiesis in the spleen and liver. The authors felt that this disease process was so different from typical AMM that it should have a separate name, acute myelofibrosis."
This was written around 1979-80. So it is somewhat out of date. But it does show that MF has stages - unfortunately.
Back To Top
What symptoms are likely/possible?
Many people have no obvious symptoms when they are diagnosed and the process of accepting the diagnosis can be difficult. Others experience the tiredness, diarrhea and other symptoms and put it down to stress, menopause or old age. In the early stages the symptoms are not usually strongly obvious. Later they may include: painful abdomen (from enlarged spleen and liver), fluid retention in the abdomen; disturbances in vision (like spots or blurring of the eyes); joint pain; bone pain (from marrow expanding into the long bones; boils orother skin eruptions (like blood blisters just under the skin).
Back To Top
What is the prognosis?
Many doctors will give quite a negative prognosis, for example: "you have years rather than decades to live"; "don't make any long term plans"; "average life span after diagnosis is four years" and so on. This is based on existing text books which usually are describing figures from some years ago.
We feel that while this may have been appropriate in the past that new treatments and new approaches as well as earlier diagnosis offer new possibilities. Each of us is an individual and should take the most positive approach to maximising the possibilities of our lives.
If you would like another example, consider the following extract from Blood Reviews, June 1991:
"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, platlet counts greater than 100x3/ul and only modest enlargement of the liver. Spleen size and sex seem to have no prognostic significance"
- Haematological Oncology, Idiopathic Myelofibrosis: Historical Review, Diagnosis and Management, written by I.M. Weinstein, M.D.
Back To Top
How could I have got this?
No one knows for sure. It seems most likely to be a specific gene abnormality which develops over a period of years. It may be triggered by exposure to harmful chemicals such as benzene or radiation; but then from a group of firemen who were all exposed to benzene some got it and others didn't. Some of us cannot identify any particular exposure. Some of us have found connections within families, but again not everyone gets it.
Although we would like to be able to point a finger at a particular cause it seems unlikely that you will be able to identify your own one unless your MF is secondary to polycythemia vera, essential thrombocythemia, chronic myelogenous leukemia or some other disease state.
Back To Top
What are the main treatment options?
The prognosis section of The National Cancer Institute, PDQ State-of-the-Art Cancer Treatment Summary, Myeloproliferative Disorders: "Agnogenic Myeloid Metaplasia -- Untreated Agnogenic Myeloid Metaplasia -- [1] For asymptomatic patients, no treatment is necessary. The profound anemia which developes in this disease usually requires red cell transfusion. Androgens are sometimes helpful in raising the hematocrit. Red cell survival is markedly decreased in some patients; this can sometimes be treated with glucocorticoids. Painful splenomegaly can be treated temporarily with chemotherapy or radiotherapy, but often requires splenectomy. [2] Acute Myelofibrosis presents with anemia, thrombocytopenia and intense myelofibrosis with circulating myeloblasts. This is probably a varient of acute megakaryocytic leukemia."
Treatment options are a function of your condition, your doctor's preference, whether you live in the United States or a country with a national health care system, etc. The following treatment options are presented in order of least invasive to most invasive.
1. Watchful Waiting This involves taking no medication and monitoring blood counts on a regular basis, which may initially be monthly, followed by bi-monthly or quarterly if results are stable.
Advantage: No chemicals are entering your system and causing effects that may be difficult to deal with. You may then in better shape if you decide later to have a bone marrow transplant. Also, with time come new treatment options.
Disadvantage: You may be anxious and feel frustrated about the lack of action.
2. Blood transfusions
The next step is to provide blood transfusions if the red blood cells fall too low. This is usually done in the hospital setting.
Advantage: If you are feeling really tired from the aenemia this may give you a boost to your energy levels by beefing up your blood.
Disadvantage: You may pick up someone else's antibodies or weird diseases in the Hepatitis group that can't yet be screened for.
3. Hydrea or other form of chemotherapy
Some doctors will suggest trying chemotherapy such as hydrea or anagrelide to control platelets and white blood counts. Other doctors believe that it is difficult to reach the bone marrow through chemotherapy and that interferon is a better first line of treatment. The problem with hydrea is that it can depress the marrow and thereby increase the risk of leukemia.
4. Interferon
Interferon is a biological response modifier which has positive effects on the immune system and also inhibits the growth of malignant cells by slowing down their motility. It also seems to have an impact on the communication process within and between cells in ways that more traditional chemotherapy doesn't. It also acts to reduce the size of the spleen.
There are several different formulations which do different things. The correct formulation has to be found for each patient and their tolerance of it established. It usually takes about six months of treatment before being able to determine if the interferon is working.
There is a recent literature report of using interferon combined with recombinant human erythropoietin and granulucyte-macrophage colony stimulating factor (Acta Haematology 1996; 96 (2): 79 - 82 authors: KL Bourantas, S Tsiara, L Christou, P Repousis, P Konstandinidou, M Bai and K Seferiadis) Treatment of r-hu-Epo plus IFN plus GM-CSF was provided to seven patients in Greece aged 48 - 72 with ideopathic myelofibrosis with beneficial results for all patients. However all showed different benefits ( reduced anemia, improved spleen, reduced marrow fibrosis (only for 2), increased white blood cells and six of the seven showed mild side effects with one showing severe side effects from the IFN.
Interferon is taken by way of injection, usually three times a week, although some doctors recommend treatment seven days a week. Some prefer lower doses to start with while others recommend as high a dose as can be tolerated in order to in effect, hit the disease hard.
People have found it best to take it at night with Tylenol to reduce impact of side effects. Some find side effects reduce after about six weeks as the body gets used to it. Others feel wretched all the time they are on it (flu like symptoms: fever, chills, fatigue, muscle aches, head ache, loss of appetite, diarrhea, dizziness, dry skin, dry mouth, slight confusion and weight loss - unfortunately you don't get to pick which symptoms you will have).
If you decide to take it try to get the smallest gauge needle possible ( for example a 29 gauge insulin type needle); find a spot that you can stand to have a needle in (many people recommend the stomach) and develop a technique to deal with it simply and easily (there are different hand and arm actions that seem to help). One secondary MF patient in our group is being treated with 6MU daily. This requires a 3 cc needle and she replaces the needle with a 30 gauge replacement after drawing the shot.
Advantages:
It replicates the body's own natural healing process and if you can find the right dosage and formulation for you it can keep your system stable for long periods - expected to be 10 - 15 years.
Disadvantages: Cost, need to inject oneself, side effects, it might not work. Its efficacy can wear off over time and the spleen can become very large and ineffective and need to be removed.
For more information about side effects of drug treatments check the Physicians Desktop Reference or do a net search on the name of the drug and see specific references to many pieces of research.
5. Bone marrow transplant
This involves the destruction of your own marrow and immune system and the subsequent replacement with someone else's. It is a complicated and hugely expensive operation with a high risk factor. However, this is the only treatment which offers the possibility of a cure.
There are two main variations on this theme. The newest form is the transplant of cord blood which is currently only available for children but which offers great hope for the future.
Placental and umbilical cord blood contains stem cells which are the master cells that generate red cells, white cells and platelets. If the cord blood is given in a transfusion it can generate renewed growth of cells. There is much less risk of Graft vs Host Disease (GVHD) because the immature stem cells don't seem to be as fussy about the HLA factors so you don't need a perfect HLA match (Human Leucocyte Factors - protein around the white cells which determine whether or not it is rejected).
Cord cell transfusions are seen as offering the potential for much less risky and less expensive treatments than bone marrow transplants. For more information about a commercial operation see: http://www.corcell.com/ Advantages: If it works you are cured.
Disadvantages: Cost, high risk of death or disease returning; ghastly process that requires up to a year of sick leave; need to find a compatible donor; need to have a committed caregiver; insurance company may refuse it as being experimental.
We have tried to research where bmts are being done for mf without much success. However we can tell you the following: Westmead Hospital Sydney Australia (large hospital with active bmt unit) 2 cases in the last 15 years, one survivor from 1995.
Fred Hutchinson Cancer Center, Seattle (specialist bmt unit does about 450 a year) 11 cases in the last 5 years including 7 with mf, 2 with PV and 2 with ET 7 cures, 2 deaths, 2 disease has returned
You will find a lot of discussion on the archives about the pros and cons of bmts as people wrestle with this most difficult decision. Should one take the high risk of a poor outcome but the chance of a cure or instead choose ongoing medication which may achieve a remission, may just hold the current state or may provide such bad side effects that the treatment can not be continued.
Back To Top
Why is a particular treatment recommended? How important are social and psychological factors in choosing a treatment option?
We have found little recognition of one's personal circumstances in choosing a treatment but in discussions on the net you will find treatment choices hotly debated. Doctors' recommendations are based on their experience, training, the policies of their hospital, the costs and who is paying for these and lastly your preference.
Our sense is that some people want the doctor to make the recommendation for them while others want to take a pro-active role and work as part of the health care team. Those of us on the net are probably more inclined towards the latter view - that's why we get on the net to find out as much as we can.
If you are a Type A personality you may find this type of illness particularly frustrating to deal with. You may want to get a treatment, and get it over with. 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 bmt; and there are not many of those around; you will live with this for the rest of your life. And your life will be different.
Those of us who have always been healthy find this very difficult. It is helpful to be able to talk it out if you are a talker and have an audience - otherwise join us on the net and share your thoughts and feelings.
Back To Top
If I choose one treatment 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 chemotherapy required prior to a bmt. Some German researchers have claimed that patients treated with interferon first have not done so well with a bmt but other doctors do not accept their results. Yet other doctors will withdraw interferon use about one year prior to a planned bmt.
Watchful waiting may be a good choice for as long as possible if you are diagnosed early, your blood counts do not pose a risk of complications such as high platelets, etc. Also, new treatments are in the process of development each year so your choices may improve with time.
Back To Top
How often do I need to have 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.
Back To Top
What about the spleen and liver-what treatment do they need that may be different?
The side effect most commonly noticed is the impact on the spleen followed by the impact on the liver. The spleen's overcompensation means that it grows large and spongey and can cause discomfort in the abdomen. If it gets really bad it may be removed. You can live without your spleen as long as you take particular care against infection or injury for the rest of your life.
Back To Top
Is this cancer?
There is some debate about this. Some say it is a hematological malignancy but not yet cancer (like pre-cancer) while others say that any disease of uncontrolled cell division is cancer. There is an excellent explanation of this on the MPD page web page under Writings of Dr. Gilbert. This is accessed at http://inform.acor.org/diseases/hematology/mpd.You may like to say to people that it is a rare bone marrow disease.
Back To Top
Where can I find out about research?
There is a huge amount of material available on the Internet about treatments and case reports and so on. As a rare disease there is not much research specifically on myelofibrosis.
Use the web page for suggestions of how and where to search; or just ask a question of the group. You might also want to search the mpd-net discussion group archives which are located at http://medinfo.org.
Back To Top
What impact will the disease have on my capacity to work?
Of course it depends on what kind of work you do and how well you feel; but in general if you pace yourself for any extra fatigue you should be able to continue in your current work.
However, at some point you may wish to reassess the role of work in your life and consider undertaking work that is not as stressful (if you find your current work stressful that is). If you are considering changing employment you will need to take into account how much you disclose to a new employer. If you plan a bone marrow transplant you will need six to twelve months sick leave from your work. Life with a chronic disease does not have as many options as life without.
Back To Top
At what point should I tell my work colleagues and what to say?
When you are newly diagnosed your emotional responses may be stronger and more erratic than you are used to. It is hard to deal with other people's reactions when you are feeling a bit wobbly yourself. If there is no impact on your work consider not disclosing for at least three months after diagnosis and then only to those who need to know. Once you have a label in people's minds it cannot be erased.
Back To Top
What effect will this diagnosis have on my capacity to obtain insurance?
Those of us who have tried to obtain insurance after diagnosis have met with generally negative responses including a flat refusal to provide life insurance. In this particular case much research information was provided to the underwriter but it had no effect.
On the other hand the same person took up new health insurance with a full disclosure and did not receive any limitations. This may be because the decision is made at a lower level where there is a list of exclusions that does not include this unusual disease. There is information on insurance issues at http://medinfo.org.
Back To Top
What is my life expectancy?
The only answer is that no one knows for sure. It may be as little as three years but it may be 10 - 15 years - or who knows it may be the full span if you have a successful bmt. What you do know for sure is that you do not have an unlimited life span and it is sensible to consider the implications on your life. In a way we are lucky that we have time to prepare - a car accident or other tragedy leaves no planning time at all.
Live your life to its fullest for every day that you have is a good philosophy to have. Research on people with cancer who live for longer than expected and who have remissions show the following factors in common:
- a sense of control about their daily lives - a sense of commitment to something outside themselves - a challenge to strive for - connectedness to a community of people
Back To Top
What about alternative medicine?
Several of us have tried a pretty wide range of alternatives to conventional medicine including the following:
- vitamins and minerals especially those focusing on the liver - Kombucha tea - Chinese herbs - Qi Gong massage - Tai Chi and Qi Gong exercises - somatic therapy - meditation - carrot, beetroot and other vegetable juice - liver cleansing diet
There is clearly a connection between one's mind and their body. So if doing these things helps to improve how you feel about yourself then it is worth doing them. Just don't expect miracle cures from them. Dealing with the bone marrow is dealing with the essence of life, the most fundamental source of life and energy. As such it is protected deep inside our bones and therefore very hard to reach to have an impact on.
Back To Top
What impact may this have on my fertility/menopause?
There is not enough known about this to be able to answer well. But if you have a bmt expect instant menopause. One woman in our mpd-net group was thrown into menopause by hydrea.
Back To Top
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.
Back To Top
How can I learn to live with so much uncertainty and those down days?
The nature of the disease is complex, uncertain and frustrating to deal with. Gather all the information you can. Don't expect to understand it all at once. This is hard stuff. Doctors had to study for years to learn about all this. There are difficult decisions to be made. Emotional challenges. Some days you will feel depressed and will need to grieve for your loss of good health. Your awareness of the suffering of others is likely to increase - you will be attending hospitals and discussing mortality rates on a regular basis. Sometimes it can all be too much and you wish you could wake up one morning and find it gone.
But there are lots of positive things you can do. Three things are even more essential now than ever before: 1. a good diet Any nutritionist can recommend a specific diet for you. Reduce fat, sugar, caffeine. Eat lots of green leafy vegetables and yellow vegetables. Many will recommend that you reduce dairy products and artificial preservatives dramatically. Eat lots of carbohydrates and as little processed food as possible. 8 glasses of water a day.
2. Exercise 20 - 30 minutes of exercise that increases your heart rate at least four days a week is the minimum needed. You feel better, sleep better and your system works better when you exercise regularly.
3. Quiet reflective time This may be meditation, prayer, music, back to nature. Whatever nurtures your spirit and gives you quiet time to reflect and rebuild your system.
Your immune system has been disturbed - anything you can do to redress that will be helpful. Review your time frames to ensure that you are living in the moment. Knowledge and action are good antidotes to down days. It may also be helpful to join a support group of people with life threatening diseases. The Internet is a great place to meet people who share your concerns.
The outcome we are seeking looks a bit like this: "I wouldn't have chosen to join this group, but now that I'm here I'm glad I've had the opportunity to learn so much about life."
Where Else Can I Go for Information?
This FAQ is a resource of MPD Research Center, Inc.
It is part of a family of resources which include:
MPD-NET internet support group
To join this discussion group, Address an email to mpd-net-request@sjuvm.stjohns.edu and in the body, put the words subscribe and your first and last name.
MPDPAGE Webpage
http://inform.acor.org/diseases/hematology/MPD
Our group's webpage has a wealth of information and links to a number of sites on the internet where you can find even more information depending upon how detailed you want to get.
MPD VOICE Newsletter
This is a quarterly "offline" newsletter published and printed by MPD Research Center. MPD Research Center members (annual fee $25) receive this free of charge. If you would like to join the center, send your check, payable to MPD Research Center, 115 E. 72nd, NY, NY 10021. For a complimentary copy of the current issue, call 1-800-HELP-MPD.
Additional FAQs
Additional FAQS on other topics are available at this website or will be shortly (Essential thrombocythemia, chronic myelogenous leukemia, agnogenic myeloid metaplasia/myelofibrosis, glossary, abbreviations, insurance issues) For information, contact Joyce Niblack (Joyce@rdz.stjohns.edu)
1-800-HELP-MPD
This is a hot line maintained by MPD Research Center, Inc.
Disease Name;
Myelofibrosis
Synonyms;
Agnogenic myeloid metaplastia
Description;
Myelofibrosis (also called agnogenic myeloid metaplasia) is a myeloproliferative disorder in which the bone marrow is initially over-active but then develops scar tissue (fibrosis). The term idiopathic means without known cause and differentiates this form of myelofibrosis from secondary myelofibrosis which may complicate other bone marrow diseases. Normal bone marrow has a very fine network of fibres supporting the blood forming tissues. In myelofibrosis this network is coarsened and thickened so that normal blood cell production is progressively reduced. As a result blood cell production begins to take place in the liver and spleen which become enlarged. These are both tissues which produce blood cells in the embryo but lose this function before birth. The production of blood cells in the liver and spleen is less efficient and so patients frequently develop anaemia.