Friend With Possible idiopathic myelofibrosis needs suggestions

[Guest guest]

Dear Group,

 

I have a friend who may have what would be described as:

 

Primary or idiopathic myelofibrosis (also known as myelosclerosis)

Idiopathic myelofibrosis, also known as agnogenic myeloid metaplasia

 

I am not very familar with this condition/disease.

 

Can anyone, here in this group, who understands this condition and

alternative methods please give me some suggestions as to possible

alternative treatments that may prove to be curative or at least helpful.

 

Here is a description from a web page.

 

http://www.leukemia-lymphoma.org/all_mat_toc.adp?item_id=9962

 

Myeloproliferative disorders are diseases in which specific types of

blood cells are overproduced by the body. There are different types of

myeloproliferative disorders, including essential thrombocythemia,

polycythemia vera and idiopathic myelofibrosis.

 

Idiopathic myelofibrosis, also known as agnogenic myeloid metaplasia,

begins with a change to a single stem cell, which then leads to both

abnormal blood cell development and fibrosis (scar tissue formation)

in the marrow.

 

This fact sheet discusses the causes, diagnosis, symptoms, current and

emerging treatments for idiopathic myelofibrosis.

 

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What is idiopathic myelofibrosis?

All blood cells begin as stem cells in the marrow. Idiopathic

myelofibrosis is one of several blood diseases that begin with an

acquired, abnormal change in a single hemapoietic (blood-forming) stem

cell in the marrow. Abnormal cell production gradually dominates

normal cell production. Eventually, the abnormal cells are made in

such large numbers that there are more of them in the marrow than

normal cells.

 

 

The stem cell change in idiopathic myelofibrosis affects the

production of red cells, white cells, and platelets. Too few red cells

are made, and usually too many white cells and platelets are made.

 

Normally, new platelets are made to replace used platelets in the body

by the following process: A proportion of stem cells in marrow develop

into a few giant cells called megakaryocytes. Each of these giant

cells breaks up into fragments and produces hundreds-to-thousands of

platelets.

 

One of the traits of idiopathic myelofibrosis is the production of too

many megakaryocytes. In turn, too many platelets are released into the

blood. In addition, the production of extra megakaryocytes causes the

release of chemicals called cytokines into the marrow. The cytokines

stimulate fibrous tissue to develop in the marrow.

 

The marrow fibrosis (scar tissue formation) gives the disease part of

its name: marrow (myelo) fibrosis. Idiopathic is the medical term

applied to diseases of unknown cause.

 

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How common is idiopathic myelofibrosis?

Idiopathic myelofibrosis is an uncommon disease that affects about 2

out of 1,000,000 people. The disease affects both men and women. It is

usually diagnosed in people between ages 50 and 70, but can occur at

any age.

 

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What causes idiopathic myelofibrosis?

Idiopathic myelofibrosis is one of several clonal diseases of the

marrow. The term clonal means that the disease originated with a

change in the DNA of a single cell. The cause for the change is unknown.

 

A small proportion of idiopathic myelofibrosis cases (about 10% to

15%) begin as either polycythemia vera or essential thrombocythemia.

 

Myelofibrosis can be a familial disorder, although this is a rare

occurrence.

 

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How is idiopathic myelofibrosis diagnosed?

Idiopathic myelofibrosis may be suspected after a routine medical

examination with findings of an enlarged spleen and abnormal blood

test results (abnormal blood counts).

 

 

One of the blood tests used to assess patients is called a complete

blood count (CBC). The CBC findings that suggest a diagnosis of

idiopathic myelofibrosis often include:

 

* A decrease below the normal range in red blood cells (anemia).

* An increase above the normal range in white blood cells.

* For about one-third of patients, platelet counts increased above

the normal range.

* For about one-third of patients, platelet counts

mildly-to-moderately lowered below the normal range.

 

In addition, a microscopic examination of the blood cells, a part of

the CBC analysis, shows misshapen red cells and immature red cells and

white cells in the blood.

 

Among patients diagnosed with idiopathic myelofibrosis, there are

variations in blood cell counts. Also, an individual patient's blood

cell counts may vary during the course of the disease. Sometimes,

patients have very little change in certain blood counts. For example,

a patient may have no elevation in white count or platelet count. In

other patients, the numbers of white cells or platelets may be lower

than normal, rather than the more common finding of higher than normal.

 

In addition to cell counts, blood tests may also show:

# Giant platelets, abnormal platelet formation and circulating dwarf

megakaryocytes.

# Elevated serum levels of uric acid, lactic dehydrogenase (LDH),

alkaline phosphatase and bilirubin.

# Decreased serum levels of albumin, total cholesterol, and

high-density lipoproteins (HDL).

To complete the diagnostic work-up, blood tests are followed by a bone

marrow examination. This test, called a biopsy, is performed as an

outpatient procedure. Local anesthesia is used for the procedure. A

special needle, inserted into the hipbone, is used to obtain a marrow

sample. Analysis of the marrow of a patient with idiopathic

myelofibrosis shows either some, or a great deal of, fibrosis.

 

 

 

There are several other blood diseases that can occasionally cause

marrow fibrosis, including leukemia and lymphoma. However, the

combination of blood and marrow laboratory findings, and the presence

of an enlarged spleen, are used to confirm a diagnosis of idiopathic

myelofibrosis.

 

A blood or bone marrow sample may also be used for a test called a

karyotype. A karyotype is done by using a microscope to examine the

size, shape, and number of chromosomes in a sample of cells. The

results of the karyotype may be helpful in making certain treatment

decisions.

 

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What are the symptoms and complications of idiopathic myelofibrosis?

About 25% of individuals with idiopathic myelofibrosis have no

symptoms at diagnosis. Patients with symptoms may have:

 

* Vague and general symptoms, such as, weakness, fatigue,

shortness of breath, weight loss, night sweats and unexplained bleeding.

* An enlarged spleen (a finding in almost all patients) that may

cause a feeling of fullness or a dragging sensation in the upper left

abdomen.

* Some patients report severe upper left shoulder pain (reflecting

blockage of blood flow to the spleen).

* Bone pain, especially in the lower extremities. However, this

symptom is uncommon.

 

 

 

Idiopathic myelofibrosis may be complicated by:

 

* Fibrohematopoietic tumors (masses containing developing blood

cells), which may form outside the marrow in any tissue in the body.

Untreated tumors may block or compress parts of the body.

* Portal hypertension, a condition that occurs when blood flow in

the portal vein (a major blood vessel that carries blood to the liver)

is slowed down from an excess of blood flow from the spleen.

* Esophageal varices are veins that have expanded and can rupture

into the stomach or esophagus, and cause bleeding. Varices are caused

by the heavy blood flow from an enlarged spleen to the liver. The

liver cannot absorb the increased flow. In order to handle the extra

blood flow, some of it is re-directed through veins in the stomach and

esophagus, causing these veins to expand.

 

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What are the current treatments for idiopathic myelofibrosis?

Treatment for idiopathic myelofibrosis is aimed at relieving symptoms

and reducing the risk of complications. Blood transfusion, replacement

of iron and folate, and drug therapies are generally important aspects

of care. Treatment may also include radiation therapy or surgery.

 

Patients who are symptom-free generally are not treated. A very large

proportion of symptom-free patients remain stable for years without

requiring treatment.

 

There is currently no cure for idiopathic myelofibrosis. However,

allogeneic stem cell transplantation (see below) may be a potentially

curative option for a small number of younger patients.

 

 

Specific treatments for the symptoms of the disease include:

Chemotherapy:

Hydroxyurea (Hydrea®) has become the preferred and most commonly used

chemotherapeutic agent. The effects of hydroxyurea are to:

 

* Decrease very high platelet counts.

* Decrease size and associated complications of an enlarged spleen.

* Decrease or eliminate night sweats and weight loss.

* Improve hemoglobin levels.

* Occasionally, decrease the degree of marrow fibrosis.

 

Interferon alpha is a synthetic version of a substance made by cells

in the body to fight infection and tumors. This drug has been used in

the treatment of idiopathic myelofibrosis for enlarged spleen, bone

pain, and thrombocytosis.

 

Androgens are drugs that are synthetic versions (analogs) of male

hormones. These agents can promote red cell production and are used to

relieve the symptoms of anemia. Oxymetholone or danazol (Danocrine®)

are two examples of androgens. About one in three patients has

improvement of anemia or a low platelet count with androgen treatment.

 

Due to the toxic effects of androgens on the liver, treatment with

these drugs includes using blood tests and ultrasound imaging to track

liver functions. Androgens may cause facial hair growth or other

masculinizing effects in women.

 

Glucocorticoids. Patients with significant anemia may benefit from

treatment with glucocorticoids, such as prednisone. Glucocorticoids

are steroid compounds and are used to treat many conditions. About one

in three patients have improvement of anemia with prednisone

treatment. In children, high-dose glucocorticoid therapy has been

reported to relieve marrow fibrosis and improve blood cell development.

 

Bisphosphonates, for example, etidronate or zoledronic acid (Didronel®

or Zometa®), may relieve bone pain and improve blood counts.

 

 

Anagrelide is a drug that may be used to treat a very high platelet

count. It may be used to lower an increased platelet count following

surgical removal of the spleen (see Splenectomy below).

 

Radiation therapy may be useful for a small number of patients to

treat an enlarged spleen, bone pain and tumors outside the marrow.

 

Splenectomy. The spleen can be removed by surgery if it is very large

and is a cause of very low platelet count, severe anemia, or portal

hypertension. This procedure is called a splenectomy. The decision to

do a splenectomy is based on weighing the individual's benefits versus

the risks. Idiopathic myelofibrosis patients who undergo surgery need

to be evaluated prior to surgery and monitored post-surgery for

increased risk of bleeding complications.

 

Stem cell transplantation. In certain circumstances, high dose

chemotherapy and radiation therapy, followed by stem cell

transplantation, is an accepted treatment to restore the body's

ability to make blood and immune cells. This procedure can be

autologous (using a patient's own stem cells, which are collected

prior to high-dose chemotherapy) or allogeneic (using stem cells from

either a related or unrelated, matched donor).

 

For idiopathic myelofibrosis patients, stem cell transplantation can

be difficult if fibrosis is extensive. However, if a well-matched

donor is available, allogeneic stem cell transplantation has the

potential to restore normal marrow function and may cure the disease.

Generally, only certain patients, younger than age 50, may be

considered for this procedure, excluding the majority of idiopathic

myelofibrosis patients.

 

 

Allogeneic stem cell transplantation can cause severe problems,

including fatalities:

 

* There is a high risk of toxicity from the high-dose chemotherapy

and radiation given prior to this procedure.

* Another risk is that donated stem cells sometimes attack healthy

tissues in a reaction called graft-versus-host disease (GVHD), causing

possibly fatal damage to liver, intestines, skin and other organs.

 

At present, the number of reported studies and the number of study

patients are too small to allow definitive comment regarding the role

stem cell transplantation plays in treatment of this disease. Research

studies (clinical trials) are underway to investigate the safety and

effectiveness of modified stem cell transplantation to reduce risks

and extend the age limits for patients. (See, What are the emerging

therapies for idiopathic myelofibrosis?)

 

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What is the prognosis for idiopathic myelofibrosis?

The average survival time after a diagnosis of idiopathic

myelofibrosis is about five years. However, about 20 percent of

patients are still in treatment 10 years after diagnosis with

idiopathic myelofibrosis. Prognosis factors that may be indicative of

better outcomes are: absence of abnormal chromosomal changes,

hemoglobin levels above 10g/dL and younger age.

 

About 10 percent of persons with idiopathic myelofibrosis are at risk

of developing acute myelogenous leukemia. The presence of an abnormal

karyotype (chromosomal changes) increases an idiopathic myelofibrosis

patient's risk of developing leukemia.

 

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What are the emerging treatments for idiopathic myelofibrosis?

Researchers are looking for more effective ways to treat idiopathic

myelofibrosis. One method is to conduct clinical trials (research

studies) of new therapies or combinations of therapies. Some

treatments recently or currently under examination for idiopathic

myelofibrosis in clinical trials include:

 

 

Thalidomide (Thalomid®) is currently used in the treatment of myeloma

and other conditions. In studies with idiopathic myelofibrosis

patients, thalidomide has been associated with improvements in anemia,

platelet count, enlarged spleen or constitutional symptoms, such as

night sweats, weakness, fatigue and shortness of breath.

 

Some patients treated with this drug have undesirable increases in

platelet count and white cell count. The use of low-dose thalidomide

with a tapering dose of prednisone has been reported to result in a

higher response rate in anemia and less toxic side effects than

higher-dose thalidomide alone.

 

RAD001 (Everolimus®) is a new drug that blocks proteins that are

important in the development and growth of cancer cells. RAD001 is

approved in Europe as an immunosuppressive agent in organ transplant

patients. It is currently being studied in clinical trials as an agent

for delaying tumor progression or recurrence in several blood cancers

including idiopathic myelofibrosis.

 

Modified allogeneic stem cell transplantation is a treatment that is

being used to treat other types of blood cancers in an attempt to

achieve the benefits of allogeneic stem cell transplant while reducing

the risks of the procedure.

 

Modified transplants are under study in clinical trials to determine

their safety and effectiveness for patients with idiopathic

myelofibrosis. Study patients are given:

 

* Induction-therapy, which will include the drugs fludarabine,

cyclophosphamide, etoposide, doxorubicin, vincristine, prednisone and,

in some cases, rituximab, to prevent rejection of donated stem cells.

* Reduced-intensity chemotherapy and donation of Th2 immune cells

(rather that T cells that are used in allogeneic stem cell

transplantation).

* Treatment with methotrexate and cyclosporine to reduce the risk

of serious GVHD.

 

For more information speak to your physician or a hematologist (a

physician who specializes in blood disorders). You can also contact

The Leukemia & Lymphoma Society.