Myeloproliferative Disorders

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What is the Bone Marrow?
What are Myeloproliferative Disorders?
How are Myeloproliferative Disorders detected?
What are staging and grading?
How are Myeloproliferative Disorders treated?
What are the side effects of treatment for myeloproliferative disorders?
What is the importance of follow up?
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What is the Bone Marrow?

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The bone marrow is a spongy tissue, which is found mainly in the large bones in the body. The bone marrow is responsible for production of most of the blood's formed elements, which include the red blood cells (carriers of oxygen and other materials to all tissues of the body), white blood cells (fighters of infection), and platelets (clotters of blood).

Usually, the bone marrow makes cells called blasts that ultimately mature into various types of blood cells, and each of these types of blood cells have specific jobs to do in the body.

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What are Myeloproliferative Disorders?

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These are diseases of the bone marrow in which too many cells of a certain type are produced by the bone marrow. It is almost exactly the opposite pathology from myelodysplastic disorders.

Four types of myeloproliferative are known:
Polycythaemia Vera.
Essential thrombocythaemia.
Chronic myelogenous leukaemia.
Agnogenic myeloid metaplasia.
Chronic myelogenous leukaemia affect cells that are developing into special white blood cells called granulocytes.

Polycythemia Vera means there are too many red blood cells made by the bone marrow and there is a huge buildup of the same in the blood.The spleen (an organ located in the left side of the upper abdomen that makes lymphocytes and filters senescent or old red blood cells from the blood) may enlarge because the extra blood cells sequester or collect there. The person may have severe itching all over the body.

Agnogenic myeloid metaplasia is a condition in which the red blood cells and certain white blood cells called granulocytes do not mature in the proper manner. The red blood cells look like tear drops instead of flat discs. The spleen enlarges and there are very few mature-functioning red blood cells for carrying oxygen, thus causing anaemia.

Essential thrombocythaemia
is a condition in which the number of platelets in the blood is much higher than normal without any known cause, but the other cells or formed elements in the blood are absolutely normal. Because of the excessive number of platelets, the viscosity of the blood is greatly increased and it does not flow in the normal manner.

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How are Myeloproliferative Disorders detected?

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A doctor may have to perform a bone marrow biopsy, in which a needle is inserted into a bone, usually the breastbone or one of the hipbones, and a small amount of bone marrow is taken out and looked at under the microscope.

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What are staging and grading?

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These are terms with which you must become familiar, if you are dealing with any form of cancer.

When we stage a cancer, we try to establish carefully, the degree of spread of the cancer and if indeed there is spread, to what extent and involving which organs.

The grading of a cancer is a microscopic issue, in which the pathologist lets you know how aggressive this particular type of cancer is; well differentiated means less aggressive, moderately differentiated intermediately aggressive, and poorly differentiated more aggressive.

Both grading and staging help your clinician to establish the prognosis or how serious your disease is, and what is going to be the likely outcome.

Staging may require additional imaging tests such as CT scan, MRI, sonography, IVU, bone scan, or chest x-ray.

There is no known staging for these diseases.Treatment depends on the type of disorder which is encountered.

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How are Myeloproliferative Disorders treated?

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A lot depends on the patient's constitution, the grade of his disease and its staging. Patients are usually treated by a team of specialists which utilizes a multipronged approach. This includes an hematologist, a medical oncologist and a radiotherapist. The plan of treatment is tailored to fit a patient's requirements.

Treatment strategies

The bastion for treatment is Chemotherapy.

The best attempt to control these cancer cells circulating in the body and lodged at various places is by using systemic therapy (therapy which affects the entire systems of the body) which is in the form of injections or oral drugs. This form of treatment is called chemotherapy.

This form of treatment is given in a cyclical manner (each set of drugs is repeated usually after every 3-4 weeks).

Phlebotomy is a procedure in which the blood from the body is removed by putting a needle in the vein. This treatment is specifically used for polycythemia vera to lower the amount of blood in the body.

A special machine may be used to filter platelets from the blood. This procedure is known as plateletpheresis.

Radiation therapy involves the use of high energy, penetrative rays to destroy cancer cells. It affects cancer cells only in the zone treated. Radiation therapy is also employed for palliation i.e. control of symptoms alone in an advanced cancer.

Radiation therapy can also be used in adjunct to surgery or chemotherapy, either before or after.

Teletherapy or external radiation is given via a machine remote from the body while brachytherapy or internal radiation is given by implanting a radioactive source within the involved tissues. Patients may or may not require both modalities of radiation.

Radiotherapy, after initial planning, usually takes just 5 to 10 minutes per day, 5 days a week for about 6 weeks. This time period is flexible depending upon the modality of radiation used.

Radiation in these disorders is usually given in the form of teletherapy. Radiation can be used to palliate symptoms.

P 32 is a radioactive source, which may be given in the department of nuclear medicine by putting a needle in the vein and then infusing the drug. It can lower the number of red blood cells being manufactured by the bone marrow.

Patients of agnogenic myeloid metaplasia may get hormones called glucocorticoids, which make the red blood cells live longer. Androgenic hormones can also be used in this disease to make the bone marrow produce more mature red blood cells.

Surgery may be performed to remove the spleen if it is excessively swollen. This procedure is called splenectomy.

Biological therapy employs Biological Response Modifiers (BRM's), which are substances that use the body's own immune system, either directly or indirectly, to fight cancer or to lessen the side effects of the anti cancer drugs. Some examples of BRM's are interferon-alfa and interleukin-2.

Polycythemia vera may be treated by one of the following options:
A phlebotomy.
Chemotherapy.
P 32 radioisotope therapy.
Biological therapy.
Essential thrombocythaemia may be treated by one of the following options:
Chemotherapy.
Plateletpheresis.
Biological therapy.
Agnogenic myeloid metaplasia may be treated by one of the following options:
If no symptoms are present, no treatment is required and the doctor just adopts a wait and watch policy. Sometimes a blood transfusion may be required if anaemia is quite severe.
External radiation to the spleen and chemotherapy or biological therapy to reduce the pain caused by the enlarged spleen.
Splenectomy.
BMT (bone-marrow transplantation.)
Biological therapy.

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What are the side effects of treatment for myeloproliferative disorders?

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Unfortunately treatment for cancer does cause damage to the healthy tissues.

Please ask the clinician about any possible side effects before any form of treatment commences.

The various drugs in chemotherapy cause a varied spectrum of side effects. The severity and variability of these symptoms are very individualistic, changing from patient to patient.

Some of the common side effects are:
Skin rashes.
Loss of hair.
Diarrhea.
Vomiting.
Tingling and numbness in the fingers and toes.
Hearing loss.
Most are temporary and recede after therapy is over. Hair growth gradually starts after cessation of chemotherapy.

The medical oncologist will usually be able to reduce the severity and spectrum of these side effects.

The psychology of the patient is very important during therapy. Better psychologically prepared the patient is, better are his chances of having decreased side effects. The patient should drink large quantities of water while the therapy is in progress, and preferably avoid uncooked or raw food. Water should be filtered or boiled. Any relative or person who has any sort of infection such as common cold should be asked to desist from coming close to the patient.

The effects of radiation depend upon the dose of radiation, the size of the area radiated, and the number and size of each fraction.

The commonest side effect is extreme fatigue. Although bed rest is good, most radiotherapists advise the patient to be as mobile as possible.

Another common problem is that of radiation dermatitis in which the skin covering the radiated area becomes red, dry, itchy, and may show signs of scaling off. This will slowly settle down after radiation ceases, but there may be a permanent 'bronzing' of the skin. It is important to note here that this skin problem is associated only with teletherapy or external radiation therapy.

Radiation also may cause nausea and vomiting, diarrhea, urinary discomfort.
There may also be a fall in the white blood cells, which are needed by humans to fight infection.

Usually the radiotherapist can suggest the drugs and diet necessary to alleviate such problems.

Biological therapy
The side effects commonly encountered with this therapy are as follows:
Low grade fever.
Rashes and bruises.
Nausea and vomiting (usually mild).
All these problems disappear on cessation of therapy.

The riskiest problem as far as bone marrow transplantation is concerned is GVHD or graft versus host disease. In this, the donated bone marrow attacks the patient's tissues and blood, and causes severe reactions ranging from effects on the liver, to the skin and to the digestive system.

GVHD can range from being very mild to very severe and can occur any time after the transplant, even many years later. Drugs are usually given along with GVHD, and subsequently in the years following the transplant in order to prevent GVHD sort of reactions.

The patient's also face an increased risk of bleeding, infection, or other side effects associated with the immunocompromised.

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What is the importance of follow up?

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The importance of follow-up cannot be overemphasized. It is a fatal fallacy to assume on the patient's part that once the primary or the first phase of treatment is over, then he or she is cured. It must be stressed here that cancer has a notorious proclivity of coming back again and again. The only way to fight this is to pick up any problem when it is still early, so that it can be nipped in the bud. And the only way to do this is to follow up when the doctor calls you for the next visit. Each such visit will include a detailed history, a physical examination (including an internal i.e. a rectal or vaginal examination), a chest x-ray, an ultrasonography or a CT scan, and various other blood studies as indicated.

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