indiacancer.org - Chronic Myeloid Leukaemia

Chronic Myeloid Leukaemia

		What are Granulocytes? What is Bone Marrow?
		What is Chronic Myeloid Leukaemia ?
		How does CML present?
		How is CML detected?
		What is staging and grading?
		How is CML treated?
		What are the side effects of treatment for CML?
		What is the importance of follow up?

What are Granulocytes? What is Bone Marrow?

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 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.

The bone marrow produces a particular type of cell line called the myeloid line and the blasts of the myeloid line ultimately mature to form particular white blood cells called granulocytes. Granulocytes like lymphocytes are infection-fighting cells. However, their mechanism is slightly different. Granulocytes do not produce antibodies to fight infections.

The lymphocytes are another particular type of infection-fighting white blood cells which are formed in the bone marrow and which circulate along with the blood.

Lymph is a colorless watery fluid present in lymph vessels.Lymph vessels are transparent thin tubes, which traverse all the systems in the body akin to the circulatory system of the blood. At various points along their route, they come to junctions or stops, which are known as lymph nodes. Lymph nodes are small, bean-shaped organs, which harbor clusters of lymphocytes. They also help to a smaller extent in the production of lymphocytes. Lymph nodes are clustered in large groups in the neck, in the back of the abdomen, in the pelvis and under the armpits. The lymph nodes and the spleen, the thymus, the tonsils, and the bone marrow are all part of the reticuloendothelial system.

The spleen is 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.

What is Chronic Myeloid Leukaemia ?

Leukaemia can be rapidly progressive with many, many immature cells, in which case it is known as acute leukaemia or it can be slowly progressive with more mature, more normal looking cells, in which case it is known as chronic leukaemia.

CML or chronic myeloid leukaemia is a slowly progressive leukaemia and usually occurs in people who are middle aged or older than that, but it can also be seen sometimes in children. In the first stages of CML, most people do not have any symptoms at all.

In most people with CML, the nuclear material in the leukaemia cells has a feature called the Philadelphia chromosome, which is not normal. The Philadelphia chromosome is a part of the person's abnormal genetic makeup.

How does CML present?

CML being an insidious disease, progresses very slowly and initially there may be no symptoms at all. As more and more leukaemia cells are added to the blood stream, the patient may start becoming symptomatic.

This could be an increase in the size of the lymph nodes or in the size of the spleen or the liver.

There may be a persistent feeling of fatigue.

The patient bleeds spontaneously and easily from multiple sites.

How is CML detected?

If any of these symptoms or more symptoms which can be described by a doctor present, then a visit to him is mandatory and this would include a physical examination and certain blood tests.

Blood tests may be quite thorough and detailed and quite a few of them may be done because leukaemias have to be absolutely properly classified.

The other test, which a doctor may have to perform is 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.

The doctor also may have to order a lumbar puncture, in which a needle is inserted through the back to take a small sample of the cerebrospinal fluid, which is the lubricating and nourishing fluid surrounding the brain and the spinal cord. Once the cells and the type of leukaemia have been adequately classified, then the treatment strategies can be mapped out.

Additional tests may also be ordered by the doctor, such as imaging investigations including an ultrasound of the abdomen or a CT scan of the abdomen, a CT scan of the chest or the brain or an MRI and chest x-rays.

What is staging and grading?

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 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 of the abdomen, IVU, Bone scan or chest X-ray.
CML once diagnosed may have to be evaluated to check if there is involvement of the central nervous system or the brain.

Following are the standard stages, in general terms, for CML.

Stage I The chronic phase, in which a few blast cells (immature cells having the capability of differentiating into more mature specific types of cells) are found in the blood and bone marrow but there are no symptoms of leukaemia. This phase may last from several months to several years and is very difficult to detect.

Stage II. Accelerated phase, where more blast cells start pouring into the blood from the bone marrow and there are fewer and fewer normal cells.

Stage III. The blastic phase or the blast phase in which more than 30% of the cells in the blood or the bone marrow are blast cells. The blast phase of CML is sometimes called a blast crisis. Sometimes blast cells form tumours outside the bone marrow in places such as the bones or in the lymph nodes.

Stage IV Refractory CML is one in which the leukaemia cells do not respond to any form of therapy.

How is CML treated?

	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. Unlike the common public perception, most leukaemias have some sort of treatment. The bastions of treatment for CML are chemotherapy and radiation. Both these therapies may also have to include treatment for complications of the leukaemia such as infection or bleeding. Biological therapy may also be an add-on and surgery is used selectively in certain cases. The best attempt to control leukaemia 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.) Chemotherapy can also be used in combination with surgery, radiotherapy or both, either before or after. 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 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 CML is usually given in the form of teletherapy. If the spleen is swollen then it can cause tremendous harm to the body by eating up the red blood cells. Thus, however many normal red blood cells may be produced by the body, they are all destroyed by the hyperactive spleen in which case the doctor may have to perform a splenectomy, a surgery in which the spleen is removed. However this particular situation is a rarity. 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. Infection is a very common problem in patients with CML and substances called immunoglobulins are given to prevent infections primarily. Extra lymphocytes, which may cause clogging of blood vessels may have to be filtered out by a special machine and this procedure is called leukapheresis. Bone marrow transplantation is an option in which the entire bone marrow of the patient is replaced with healthy bone marrow. First of all the bone marrow in the body is destroyed with high-dose chemotherapy in association or without radiation therapy. The healthy bone marrow is then taken from another person whose tissue has the same HLA matching as the patient's. HLA is a kind of tissue matching, which is required to be done before any kind of tissue is transferred from a donor to a recipient in order to prevent a reaction and the donor's body from rejecting the entire tissue sample. The donor may be an identical twin, which always produces the best match, or a sibling such as a brother or sister, or a totally unrelated person. The healthy marrow from the donor is given to a patient just like saline, that is, through a needle in the vein and the marrow replaces the marrow that has been destroyed. A bone marrow transplant or a BMT using marrow from a relative or person not related to the patient is called an allogenic BMT. Autologous BMT is a type of transplant in which the bone marrow is taken from the patient before radical chemotherapy, and then is treated with drugs to kill any cancer cells. Then the marrow is cryogenically frozen to save it, and high-dose chemotherapy is given with or without radiation to the patient to destroy the remaining marrow. The frozen marrow is now thawed out and reintroduced into the patient through a needle in a vein. Maximum chances for recovery occur if the doctor chooses a hospital that has done a significant number of BMTs with very less evidence of either septicemia, infection, or rejection. Yet another type of autologous transplant is called a peripheral blood stem cell rescue transplant. In this, the patient's blood is passed through a machine that removes the immature cells from which all blood cells develop (the stem cells) and then returns the blood to the patient. This procedure, known as leukapheresis, usually takes 3 to 4 hours to complete. The stem cells are now treated with drugs to kill any cancer ingredient in them and are then cryogenically frozen until they can be transplanted to the patient. This may be done in association or disassociated from an autologous bone marrow transplant. Chronic CML One of the following options may be entertained:
		High-dose chemotherapy with radiation therapy followed by BMT.
		Biological therapy.
		Chemotherapy to reduce the number of white blood cells.
		Chemotherapy and radiation therapy followed by BMT.
		Splenectomy, which is surgery to remove the spleen.
	Accelerated CML One of the following options may be entertained:
		BMT.
		High-dose chemotherapy.
		Biological therapy.
		Chemotherapy to reduce the number of white blood cells.
		Other chemotherapeutic options.
		Repeated transfusions of blood or blood products to relieve symptoms.
	Blast-phase CML or blast crisis. One of the following options may be entertained:
		New experimental chemotherapeutic drugs or multi-modality combinations of drugs.
		Standard chemotherapy.
		BMT.
		Palliative chemotherapy to relieve the symptoms associated with the CML.
		High-dose chemotherapy.
		Radiation therapy for palliation of symptoms caused by the tumours in the bone.
	Meningeal CML, i.e., CML which is present in the meninges, which are the layers covering the brain and the spinal cord. One of the following therapies may be entertained:
		Intrathecal chemotherapy or chemotherapy which is injected directly into the spinal canal.
		Radiation therapy to the brain or cranial irradiation.
	Refractory CML. A difficult proposition and usually unforgiving as far as results are concerned. The treatment depends on many factors and the patient may decide to enroll himself or herself in a clinical trial, which is trying out new experimental drugs.

What are the side effects of treatment for CML?

	Unfortunately, treatment for cancer does cause damage to healthy tissues. Please ask the clinician about any possible side effects before any form of treatment commence. The various drugs used 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:
		Infections.
		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 (chemotherapist) will usually be able t reduce he severity and spectrum of these side effects. The psychology of the patient is very important during therapy. The better psychologically prepared the patient is, the better are his or her chances of having decreased side effects. The patient should drink large quantities of liquids while therapy is in progress, and preferably avoid uncooked or raw food. Water for drinking should be filtered or boiled. Any relative or person who has any infection such as common cold should be asked to desist from coming close to the patient. The effects of radiation depend on the dose of radiation, the size of the area radiated, and the number and size of each fraction employed. 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 causes nausea and vomiting, diarrhea and urinary discomfort. There may also be a fall in the white blood cells, which are needed by humans to fight infections. 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.

What is the importance of follow up?

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 ), chest x-ray, an ultrasonography or a CT scan, and various other blood studies as indicated.