Leukemia is a medical condition affecting the blood. Firstly, let’s talk about the normal blood system. In every adult individual, there is present 5 to 6 litres of blood. The components of the blood include:
1. Red blood cells which help carry Oxygen to the tissues to Help in their daily function of maintaining healthy balance.
2. White blood cells which are the body soldiers. When an infectious agent enters the body, the white blood cells respond by fighting these agents, though numerous ways to ensure the body remains healthy.
3. Platelets: These move to sites of injury to ensure bleeding does not continue which may lead to death. Therefore, they are important in blood clotting.
4. Plasma: This is the liquid in which the above 3 components are suspended. The plasma contains other numerous essential components too like proteins, salt, and enzymes which all help to maintain body balance.
Leukemia in simple terms can be defined as cancer of the blood. The primary component of the blood which is affected is the white blood cell. In Leukemia, the white blood cells are present in numbers far above upper limit of normal. There may be laboratory and geographical differences. However, in average, every individual has between 4 to 11 billion white blood cells in a litre of blood. Remember, I mentioned earlier that every individual has between 5 to 6 litres of blood. So you can estimate how much white blood cells are present in the body when in healthy state.
One would expect that since white blood cells are soldiers of the body, the more they are, the safer or healthier the body should be. In Leukemia, this is not the case. For lack of a better word, the abnormally numerous white blood cells are actually ‘USELESS’. The white blood cells in leukemia lack their normal functions of fighting infection, therefore, the individual is vulnerable to all kinds of infectious diseases.
Let me mention that the white blood cells and red blood cells are produced inside the bone marrow of the long bones in the arms, forearms, thigh, and legs. The bone marrow of the sternum and waist bone is also active in production of red and white blood cells.
In Leukemia, the problem originates primarily in this bone marrow. The white blood cells are abnormally formed and therefore not useful to the body. This need for functioning white blood cells sends stronger signals to the bone marrow to produce more white blood cells to fight infection. Unfortunately because the bone marrow is diseased, more abnormal white blood cells are produced and released into the blood stream. This increase in numbers of abnormal white blood cells is essentially what we refer to as Leukemia.
The exact cause of leukemia is not known, but it is thought to involve a combination of genetic and environmental factors. Leukemia cells have acquired mutations in their DNA that cause them to grow abnormally and lose functions of typical white blood cells. It is not clear what causes these mutations to occur. One type of change in the cells’ DNA that is common in leukemias is known as a chromosome translocation. In this process, a portion of one chromosome breaks off and attaches to a different chromosome. One translocation seen in almost all cases of CML and in sometimes in other types of leukemia is an exchange of DNA between chromosomes 9 and 22, which leads to what is known as the Philadelphia chromosome. This creates an oncogene (cancer-promoting gene) known as BCR-ABL. This change in DNA is not inherited but occurs sometime in the life of the affected individual.
Most cases of leukemia are not believed to be hereditary, but certain genetic mutations and conditions can be passed along to offspring that increase the chances of developing leukemia. A condition known as Li-Fraumeni syndrome is characterized by an inherited mutation in a tumor suppressor gene known as TP53, and individuals with this condition have an increased risk of leukemia and other cancers. Other hereditary conditions that can increase the risk of developing leukemia include:
neurofibromatosis type 1,
ataxia telangiectasia, and
You may look those up. In summary: no known cause and it is believed to be multifactorial.
Risk factors include:
1. Exposure to radiation
3. Exposure to certain chemicals like benzene
4. Family History (if someone in the Family had Leukemia).
Types of Leukemia
Now let’s look at the types
We group leukemia by how fast they develop and the type of cell involved.
1. Acute Leukemia develops very fast within weeks
2. Chronic Leukemia develops slowly – over years but may accelerate at some time to look like acute leukemia.
To understand the type of cells involved, I’ll do a little explanation.
There are cells in your bone marrow that possess the ability to form any type of blood cell. As they differentiate (changing into cells we can recognize), we would have
1. Lymphoid – forms what we call lymphocytes – B and T cell types
2. Myeloid – forms red blood cells, platelets (from our last lecture), some neutrophils and other blood cells.
This diagram illustrates the cell lines (don’t bother about the details, just focus on Myeloid and Lymphoid).
So, when we combine both classification, we can have:
1. Acute Myelogenous Leukemia
2. Acute Lymphoblastic Leukemia
3. Chronic Myelogenous Leukemia
4. Chronic Lymphocytic Leukemia
There are others, but these are the main ones.
1. Acute lymphocytic leukemia (ALL, also known as acute lymphoblastic leukemia) is the most common type of leukemia in children, but it can also affect adults. In this type of leukemia, immature lymphoid cells grow rapidly in the blood. It affects over 6,000 people per year in the U.S.
2. Acute myeloid leukemia (AML, also called acute myelogenous leukemia) involves the rapid growth of myeloid cells. It occurs in both adults and children and affects about 21,000 people each year in the U.S.
3. Chronic lymphocytic leukemia (CLL) is a slow-growing cancer of lymphoid cells that usually affects people over 55 years of age. It is estimated to affect about 20,000 people in the U.S. every year. It almost never occurs in children or adolescents.
4. Chronic myeloid leukemia (CML, also known as chronic myelogenous leukemia) primarily affects adults and occurs in about 8.950 people every year in the U.S.
1. Bone pain. One may think the child (if it is a child) is a Sickle cell disease Patient
2. Unexplained fever
3. Easy fatigability/weakness
4. Easy bruising
5. Fullness after a meal/poor appetite
6. Frequent infections
7. Dull pain in abdomen
8. Weight loss
9. Painless mass in the neck region or waist (inguinal).
When the fever and dull abdominal pain starts, one may be tempted to think it is the age old combo of malaria/typhoid. Especially if it is in a child. Chronic forms may be asymptomatic for years.
Please note: an index of suspicion is raised in repeated fever, weight loss and some painless swelling in the neck or parts of the body. Please don’t take it for granted.
Diagnosis and Workup of Leukemia
When one walks into a Hospital to see a Doctor, possibly for screening or just for some symptoms, a Doctor takes a History (asking questions about the disease, your life and family as relates to health) before proceeding to examine such one physically and sending them for investigations. This is the traditional Clinical approach to a Client and that’s exactly what your Doctor will be doing. To break it down, diagnosis of Leukemia has the following components:
2. Physical examination (will look for lymph node lumps alongside features of anaemia and others)
3. Investigations (will check your blood mostly)
Hematologists are specialist Doctors who diagnose and treat blood diseases, including leukemia; hematologist-oncologists treat blood diseases like leukemia, as well as other types of cancers.
In addition to a medical history (asking about symptoms and risk factors) and a physical exam to look for signs of leukemia (lymph node enlargement, enlargement of spleen), the diagnosis of leukemia typically involves laboratory studies of a blood sample. Abnormal numbers of blood cells may suggest a diagnosis of leukemia, and the blood sample may also be examined under the microscope to see if the cells appear abnormal. A sample of the bone marrow may also be obtained to establish the diagnosis. For a bone marrow aspirate, a long, thin needle is used to withdraw a sample of bone marrow from the hip bone, under local anesthesia. A bone marrow biopsy involves insertion of a thick, hollow needle into the hip bone to remove a sample of the bone marrow, using local anesthesia.
Cells from the blood and bone marrow are further tested if leukemia cells are present. These additional tests look for genetic alterations and expression of certain cell surface markers by the cancer cells (immunophenotyping). The results of these tests are used to help determine the precise classification of the leukemia and to decide on optimal treatment.
Other tests that may be useful include a chest X-ray to determine if there are enlarged lymph nodes or other signs of disease and a lumbar puncture to remove a sample of cerebrospinal fluid to determine if the leukemia cells have infiltrated the membranes and space surrounding the brain and spinal cord.
Imaging tests such as MRI and CT scanning can also be useful for some patients to determine the extent of disease.
There are a number of different medical approaches to the treatment of leukemia. Treatment will typically depend upon the type of leukemia, the patient’s age and health status, as well as whether or not the leukemia cells have spread to the cerebrospinal fluid. The genetic changes or specific characteristics of the leukemia cells as determined in the laboratory can also determine the type of treatment that may be most appropriate.Your Doctor and managing team will determine all that.
Watchful waiting (expectant management) may be an option for some people with a chronic leukemia who do not have symptoms. This involves close monitoring of the disease so that treatment can begin when symptoms develop. Watchful waiting allows the patient to avoid or postpone the side effects of treatment. The risk of waiting is that it may eliminate the possibility of controlling the leukemia before it worsens.
Treatments for leukemia include:
1. chemotherapy (major treatment modality for leukemia),
2. radiation therapy,
3. biological therapy,
4. stem cell transplant. Combinations of these treatments may be used.
Surgical removal of the spleen can be a part of treatment if the spleen is enlarged.
There’s also the psychological support given to Patients with Leukemia, like other cancers.
Acute leukemia needs to be treated when it is diagnosed, with the goal of inducing a remission (absence of leukemia cells in the body). After remission is achieved, therapy may be given to prevent a relapse of the leukemia. This is called consolidation or maintenance therapy. Acute leukemias can often be cured with treatment.
Chronic leukemias are unlikely to be cured with treatment, but treatments are often able to control the cancer and manage symptoms. Some people with chronic leukemia may be candidates for stem cell transplantation, which does offer a chance for cure.
Many patients opt to receive a second opinion before beginning treatment for leukemia. In most cases, there is time to receive a second opinion and consider treatment options without making the treatment less effective. However, in rare cases of very aggressive leukemias, treatment must begin immediately. Someone should discuss with a doctor the possibility of obtaining a second opinion and any potential delays in treatment. Most doctors welcome the possibility of a second opinion and should not be offended by a patient’s wish to obtain one.
Chemotherapy is the administration of drugs that kill rapidly dividing cells such as leukemia or other cancer cells. Chemotherapy may be taken orally in pill or tablet form, or it may be delivered via a catheter or intravenous line directly into the bloodstream. Combination chemotherapy is usually given, which involves a combination of more than one drug. The drugs are given in cycles with rest periods in between.
Side effects of chemotherapy depend on the particular drugs taken and the dosage or regimen. Some side effects from chemotherapy drugs include hair loss, nausea, vomiting, mouth sores, loss of appetite, tiredness, easy bruising or bleeding, and an increased chance of infection due to the destruction of white blood cells. There are medications available to help manage the side effects of chemotherapy.
Some adult men and women who receive chemotherapy sustain damage to the ovaries or testes, resulting in infertility. Most children who receive chemotherapy for leukemia will have normal fertility as adults, but depending on the drugs and dosages used, some may have infertility as adults.
Biological therapy is any treatment that uses living organisms, substances that come from living organisms, or synthetic versions of these substances to treat cancer. These treatments help the immune system recognize abnormal cells and then attack them. Biological therapies for various types of cancer can include antibodies, tumor vaccines, or cytokines (substances that are produced within the body to control the immune system). Monoclonal antibodies are antibodies that react against a specific target that are used in the treatment of many kinds of cancer. An example of a monoclonal antibody used in the treatment of leukemia is alemtuzumab, which targets the CD52 antigen, a protein found on B-cell chronic lymphocytic leukemia (CLL) cells. Interferons are cell signaling chemicals that have been used in the treatment of leukemia.
Side effects of biological therapies tend to be less severe than those of chemotherapy and can include rash or swelling at the injection site for IV infusions of the therapeutic agents. Other side effects can include headache, muscle aches, fever, or tiredness.
Radiation therapy uses high energy radiation to target cancer cells. Radiation therapy may be used in the treatment of leukemia that has spread to the brain, or it may be used to target the spleen or other areas where leukemia cells have accumulated.
Radiation therapy also causes side effects, but they are not likely to be permanent. Side effects depend on the location of the body that is irradiated. For example, radiation to the abdomen can cause nausea, vomiting, and diarrhea. With any radiation therapy, the skin in the area being treated may become red, dry, and tender. Generalized tiredness is also common while unStem cell transplant
Stem Cell transplant
In stem cell transplantation, high doses of chemotherapy and/or radiation are given to destroy leukemia cells along with normal bone marrow. Then, transplant stem cells are delivered by an intravenous infusion. The stem cells travel to the bone marrow and begin producing new blood cells. Stem cells may come from the patient or from a donor.
Autologous stem cell transplantation refers to the situation in which the patient’s own stem cells are removed and treated to destroy leukemia cells. They are then returned to the body after the bone marrow and leukemia cells have been destroyed.
An allogeneic stem cells transplant refers to stem cells transplanted from a donor. These may be from a relative or an unrelated donor. A syngeneic stem cell transplant uses stem cells taken from a healthy identical twin of the patient.dergoing radiation therapy.
Stem cells may be removed (harvested) in different ways. Typically, they are taken from the blood. They can also be harvested from the bone marrow or from umbilical cord blood.
Stem cell transplantation is done in a hospital, and it is necessary to remain in the hospital for several weeks. Risks of the procedure include infections and bleeding due to the depletion of normal blood cells. A risk of stem cell transplant with donor cells is known as graft-versus-host disease (GVHD). In GVHD, the donor white blood cells react against the patient’s normal tissues. GVHD can be mild or very severe, and often affects the liver, skin, or digestive tract. GVHD can occur at any time after the transplant, even years later. Steroids or medications that suppress the immune response may be used to treat this complication.
Because many of the treatments for leukemia deplete normal blood cells, increasing the risk for bleeding and infection, supportive treatments may be needed to help prevent these complications of treatment. Supportive treatments may also be needed to help minimize and manage unpleasant side effects of medical or radiation therapy.
Types of supportive and preventive treatments that can be used for patients undergoing treatment for leukemia include the following:
1. Vaccines against the flu or pneumonia
2. Blood or platelet transfusions
3. Antibiotics or antiviral medications to treat or prevent infections
4. White blood cell growth factors to stimulate white blood cell production (such as granulocyte-colony stimulating factor [G-CSF], made up of filgrastim [Neupogen] and pegfilgrastim [Neulasta] and granulocyte macrophage-colony stimulating growth factor [GM-CSF], made up of sargramostim [Leukine])
5. Red cell growth factors to stimulate red blood cell production (darbepoetin alfa [Aranesp] or epoetin alfa [Procrit])
6. Intravenous injections of immunoglobulins to help fight infection
Some of these measures are not present in most Hospitals in Africa. Your Doctor will be proactive and practical in the approach to treatment in your locality.
What is the prognosis of leukemia?
The prognosis of leukemia depends upon the type of leukemia that is present and the age and health status of the patient. Mortality (death) rates for leukemia are higher in the elderly than in younger adults and children. In many cases, leukemia can be managed or cured with treatments available today. In particular, childhood ALL has a very high 5-year survival rate.
Modern treatments have led to a greater than fourfold increase since 1960 in five-year survival rates for leukemia. Five-year survival rates for different types of leukemia are approximately:
AML: 27% overall, 64% for children and teens younger than 15
ALL: 71% overall, over 90% for children.
The likelihood that leukemia will recur (come back after successful treatment) depends upon the type of leukemia including the specific molecular characteristics of the cancer cells and the patient’s response to initial treatment. Some acute leukemias are successfully treated, and the patient never experiences a recurrence. In chronic leukemias, such as CML, ongoing symptoms and recurrences are common, and treatments may be directed at keeping the leukemia under control.