indiacancer.org - Acute Leukemias

Acute Leukaemia

		What are lymphocytes? What is the bone marrow?
		What are Acute Leukaemias?
		How do Acute Leukaemias present?
		How are Acute Leukaemias detected?
		What are staging and grading?
		How are the Acute Leukaemias in adults treated?
		What are the side effects of treatment for leukaemias?
		What is the importance of follow up?

What are Lymphocytes? What is the bone marrow?

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

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 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.

Lymphocytes are cells circulating in the lymph, which 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.

The thymus is a small organ, which is located beneath the breastbone and is most prominent during childhood.

The tonsils are groups of lymphoid tissue, which are present in the back of the throat and along the sides of the throat.

The bone marrow also 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.

	What are Acute Leukaemias?

Adult acute lymphocytic leukaemia or acute lymphoblastic leukaemia or ALL, as it is commonly known as, is a disease in which there are too many abnormal lymphocytes produced in the blood and the bone marrow. Lymphocytes are abnormally produced by the bone marrow and circulate in great numbers in blood, causing a large number of problems.

Developing lymphocytes are not mature enough and in their immature state itself are pumped into the blood. These lymphocytes also collect in the lymphatic tissues and make them swell up. Lymphocytes crowd out the other blood cells in the blood and bone marrow.

This produces an imbalance, because if the bone marrow cannot produce enough red blood cells to carry oxygen then anemia develops. If the bone marrow is not able to produce enough platelets, then the patient develops a difficulty in clotting and may bleed spontaneously and easily.

These cancerous lymphocytes also have a predilection to invade other organs such as the spinal cord or the brain.

Acute leukaemia can be extremely aggressive and progresses quickly either in adults or in children. It is a very difficult disease to diagnose.

Acute myeloid leukaemia affects the blast cell lines of the myeloid tissue and there is a great accumulation of immature pre-granulocytic cells. The blasts do not mature and become too numerous. These then push out other cells in a manner similar to that seen in ALL. Again, AML or acute myeloid leukaemia is a disease seen both in childhood and in adulthood. It is quite a rapidly progressive disease.

The term 'leukaemia' literally means white blood and this is because of the increase in white blood cells in the blood.

	How do Acute Leukaemias present?

	The early signs of ALL mimic so many common conditions and infective problems that often the doctor makes a mistake. The early signs are quite similar to common cold or flu, or other common diseases. If the person develops one of the following symptoms which refuses to go away such as:
		Fever.
		Persistent tiredness or weakness.
		A generalized aching in the bones or joints.
		Swollen lymph nodes.
		Bleeding from the gums (which is more common in acute myeloid leukaemia), then it is time to pay a visit to the doctor.

	How are Acute Leukaemias detected?

If such symptoms are present and the doctor decides that some kind of leukaemia may be present, then he may order blood tests to count the number of each of the different kinds of blood cells.

If there is an abnormality detected in these peripheral blood smears, then the doctor orders 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.

Investigations for acute myeloid leukaemia also follow a similar pattern. The differentiation only comes after the histopathologist has given the diagnosis by seeing the cellular morphology under the microscope.

What are 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. There are no clear cut stages for ALL, although there are distinct cellular morphologies to be seen under the microscope and by doing CD markers, which are clusters of differentiation markers, special tests to find out the type of leukaemia. ALL can be broadly classified into:
		Untreated ALL, which means that no treatment has been given prior to this particular moment in time to treat the symptomatology. There are an extreme number of white blood cells in the blood and the bone marrow and there are other signs and symptoms of leukaemia.
		ALL in remission, which means that the treatment has been given and the number of white blood cells and other blood cells in the blood and bone marrow are normal. And also there are no signs and symptoms suggestive of leukaemia at the moment.
		Recurrent or refractory ALL; the former is that in which the leukaemia has come back after going into remission. Refractory ALL is that leukaemia which has failed ever to go into remission following primary treatment.
	AML just like ALL has no staging as far as treatment is required, the choice of treatment again depends on whether the patient has been treated or not and the staging is the same, namely, untreated, or in remission, or recurrent or refractory AML.

How are the Acute Leukaemias in adults 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. This applies for ALL as well. The bastion of treatment for ALL is chemotherapy. Radiation may also be used in certain cases. And bone marrow transplant is always an option, which is to be kept in the mind. 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. 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. There are basically two phases of treatment for ALL. The first stage is known as induction. The purpose of induction is to destroy as many of the leukaemia cells as possible and put the patients into the remission state. Once in remission with no clinical signs of leukaemia, patients enter the second part of the treatment, which is called continuation or maintenance therapy. It is also sometimes known as consolidation therapy. This tries to kill any remaining leukaemia cells, which may be subclinical or just below the detectable margins. A patient may have to receive chemotherapy for up to several years to stay in comfortable remission. The patient will also have to receive radiation or chemotherapy for the brain. This is known as cranial prophylaxis. This is for several reasons:
		To prevent leukaemia cells from growing into the brain during induction therapy and remission.
		For those patients who have already got leukemia cells detected in the brain.
	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. For AML, the other option which is present is biological therapy, which tries to induce the body to fight the cancerous cells by harnessing, redirecting and amplifying the body's immunity and infection-fighting ability and also by increasing and augmenting its natural defenses against disease. Biological therapy is also known as immunotherapy or BRM, that is biological response modifier therapy. Untreated adult acute lymphoblastic leukaemia The treatment is going to be:
		Systemic chemotherapy along with intrathecal chemotherapy alone, or combined with either radiation therapy to the brain or high doses of systemic chemotherapy to prevent or treat leukaemia in the brain.
	The treatment as an adjunct will also include:
		Repeated blood transfusions.
		Antibiotics.
		Fresh frozen plasma infusions.
		Packed cell volume infusions.
		Instructions to keep the body and feet especially clean.
	Continuously, new drugs are being tested in clinical trials.
	Recurrent adult acute myeloid leukaemia.
		Systemic chemotherapy along with intrathecal chemotherapy alone, or combined with either radiation therapy to the brain or high doses of systemic chemotherapy to prevent or treat leukaemia in the brain.
	The treatment as an adjunct will also include:
		Repeated blood transfusions.
		Antibiotics.
		Fresh frozen plasma infusions.
		Packed cell volume infusions.
		Instructions to keep the body and feet especially clean.
	Continuously, new drugs are being tested in clinical trials. ALL in remission
		Short-term, high-dose chemotherapy followed by long-term, low-dose chemotherapy as consolidation.
		Allogenic bone marrow transplant.
		Autologous bone marrow transplant.
		Intrathecal chemotherapy (chemotherapy given by lumbar puncture into the brain and spinal cord area combined with either radiation to the brain or high doses of systemic chemotherapy). This is to prevent leukaemia cells from growing in the brain and the spinal cord area, otherwise known as CNS or cranial prophylaxis.
	Recurrent adult acute lymphocytic leukaemia
		Radiation therapy to palliate symptoms.
		Patients may also get a trial of bone marrow transplant.
	Untreated adult acute myeloid leukaemia is usually treated by systemic multi-drug chemotherapy. The person also may get CNS prophylaxis and, in case leukaemia cells are found in the brain, chemotherapy may be given intrathecally anyway. Adult acute myeloid leukaemia in remission. Treatment will most likely be:
		Systemic chemotherapy and including experimental new drugs.
		A clinical trial evaluating BMT versus peripheral stem cell rescue.
	Recurrent adult acute myeloid leukaemia.
		Radiotherapy plus trial chemotherapy.
		Bone marrow transplant.

What are the side effects of treatment for Leukaemias?

	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.
	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.
	Although the side effects of biological therapy vary with the type of medicine used, the common side effects are:
		Low-grade fever.
		Nausea and vomiting, which are usually mild.
		Rashes and bruises.
		Bone pains.
	All these problems disappear on cessation of therapy.

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