Leukemia means cancer of blood-forming tissues, which leads to the production of a high number of abnormal blood cells, especially white blood cells (WBCs). To understand leukemia, we need to know more about the different types of blood-forming tissues and blood cells.
The blood-forming tissues
Our body contains a factory called bone marrow, which forms blood cells. The bone marrow is a soft tissue located inside some bones, such as the hip bone, skull bones, ribs, and vertebrae. It forms the three types of blood cells: red blood cells (RBCs), white blood cells (WBCs), and platelets. These cells arise from stem cells (hematopoietic stem cells) that divide to form two types of immature cells: myeloid stem cells (myeloblasts) and lymphoid stem cells (lymphoblasts). These cells grow to be the mature blood cells; myeloblasts give red blood cells, some types of white blood cells (neutrophils, eosinophils, basophils, and monocytes), and platelets while lymphoblasts give lymphocytes.
Our body contains a factory called bone marrow, which forms blood cells. The bone marrow is a soft tissue located inside some bones, such as the hip bone, skull bones, ribs, and vertebrae. It forms the three types of blood cells: red blood cells (RBCs), white blood cells (WBCs), and platelets. These cells arise from stem cells (hematopoietic stem cells) that divide to form two types of immature cells: myeloid stem cells (myeloblasts) and lymphoid stem cells (lymphoblasts). These cells grow to be the mature blood cells; myeloblasts give red blood cells, some types of white blood cells (neutrophils, eosinophils, basophils, and monocytes), and platelets while lymphoblasts give lymphocytes.
WBCs and Leukemia
Now let’s talk about the white blood cells to understand leukemia better:
White blood cells (WBCs) or leukocytes represent only 1% of blood cells, but they play a vital role in your health. They protect you from harmful organisms and foreign bodies. They recognize the foreign and harmful antigens, destroy them, and produce antibodies to prevent the recurrence of the same infection. To do this function efficiently, many types of white blood cells are present. Each of them has a specific role in the immune process and specific antigen to fight it.
Types of white blood cells
› Neutrophils
These cells represent 45-70% of white blood cells. They protect your body from bacteria and fungi. Also, they are the first line of defense against infection as they stimulate the other immune cells to contribute to the immune response. They are also the first cells that migrate to the site of infection. They try to kill the invader (phagocytosis) and may succeed or keep the condition under control until the body develops adaptive (specific) immunity, which is more powerful. They may undergo programmed cell death to stimulate the bone marrow to produce more neutrophils. Dead neutrophils in large numbers form what we know as pus. They have a short lifespan that ranges from 6 hours to a few days.
› Eosinophils
These cells represent 2-4% of white blood cells. They fight mainly against large parasites like hookworms and tapeworms and are responsible for the allergic response in cases of drug reactions. They are abundant in the mucosa of the respiratory and digestive tracts.
› Basophils
These cells represent 0-2% of white blood cells. They are mainly responsible for the allergic response. They produce histamine and heparin. Histamine causes vasodilation and increases the blood supply to the invaded area; it also increases the permeability of the wall of blood vessels, which enables the neutrophils and other immune cells to reach the tissues. Heparin inhibits blood clotting, which improves the blood flow carrying the immune cells to the injured area. They also send signals that attract neutrophils and eosinophils to the site of infection.
› Monocytes
These cells represent 4-8% of white blood cells, and they are the largest of them. They help the neutrophils in their function (killing the invaders or phagocytosis), but perform other functions as well:
✦ They introduce the harmful organisms to the T-lymphocytes that recognize and kill them (Antigen-presenting cells).
✦ They also leave blood into tissues to become tissue macrophages. Tissue macrophages kill the infected cells (such as viral-infected cells), clean the dead cells, and attack the foreign and harmful organisms.
› Lymphocytes
These cells represent 25-40% of white blood cells. There are two subtypes of lymphocytes:
♦ T-lymphocytes: These cells recognize the infected cells -either viral or bacterial infected cells- and kill them. Also, they have a memory that saves the antigen, which enables them to respond rapidly if the same infection occurred again. Additionally, they can identify and kill tumor cells.
♦ B-lymphocytes: These cells don’t kill the antigens directly, but they produce proteins called antibodies. Antibodies bind to the surface of antigen, which prevents its harmful action and help the other immune cells to recognize and kill the pathogen.
The normal white blood cell count
We should know the normal white blood cell count and each type count, because any abnormal increase or decrease may indicate a problem.
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- Total white blood cell count: 4000-11000 cell/mm3
- Neutrophils: 3000-7000 cell/mm3 (45-70%)
- Esinophils: 50-400 cell/mm3 (2-4%)
- Basophils: 0-100 cell/mm3 (0-2%)
- Monocytes: 400-800 cell/mm3 (4-8%)
- Lymphocytes: 1700-3400 cell/mm3 (25-40%)
High white blood cell count means leukocytosis while low white blood cell count means leukopenia, and we will discuss each of them.
⇒ Now, let’s discuss high white blood cell count (leukocytosis).
High white blood cell count (leukocytosis)
A high level of white blood cells isn’t a disease, but it’s a symptom of another problem. Thus, a high level of white blood cells requires further investigations to detect the cause and control it.
Causes of leukocytosis
1- Infection (bacterial, viral, fungal, or parasitic): Elevated white blood cell count may indicate that your immune system fights infection and the bone marrow produces high levels of white blood cells to enhance the immune response.
2- Tumors of blood or bone marrow, such as leukemia: In leukemia, the bone marrow produces a very high number of white blood cells, but they are abnormal leukocytes (leukemia cells), and they are unable to do their function, which increases the risk of infection.
3- Smoking: Inhaled smoke is a foreign body that causes airway inflammation, which increases the level of white blood cells.
4- Immune disorders, including autoimmune diseases (Grave’s disease – chron’s disease)
5- Allergic disorders, such as bronchial asthma
6- Stress (emotional or physical stress) increases the level of white blood cells, but it goes back to the normal level after the end of the stressful event.
7- Trauma and injuries.
These causes may increase the total white blood cell count, but a high count of a specific type may specify the problem, such as the following:
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- High eosinophilic count indicates a parasitic infection or an allergic condition like asthma.
- High lymphocytic count indicates viral infection, tuberculosis, or tumors like some types of leukemia or lymphoma.
- High basophilic count indicates hypothyroidism or other health problems.
Symptoms of high white blood cell count
Patients with leukocytosis don’t have specific symptoms. They only have symptoms of the disease that caused this condition. Thus, if you suffer from any of these conditions, your doctor will investigate the white blood cell count. Non-specific symptoms may occur, such as fever, weight loss, fainting, and general pain.
How to lower a high white blood cell count?
Proper treatment of the underlying disease (such as infection or cancer) is essential to reduce a high white blood cell count. Also, cessation of smoking and reduction of stress help to keep the white blood cell count in the normal range.
Some foods help to keep the white blood cell count in the normal range, especially those rich in antioxidants, such as vitamin C and E, monounsaturated fats, and fibers, which found in fruits, vegetables, nuts, garlic, herbs, soy protein, and green tea. You also should avoid foods rich in calories, saturated fats, and salt.
⇒ Now, we will discuss low white blood cell count (leukopenia).
Low white blood cell count (leukopenia)
Leukopenia is a dangerous condition because it means that your body is without defense against invaders. Neutropenia and lymphocytopenia are the most common forms of leucopenia.
Causes of leukopenia
Aplastic anemia: It’s a type of anemia that occurs due to bone marrow failure, and it affects all blood components, including white blood cells. It may be congenital or acquired.
Tumors and their treatment: Tumors like leukemia, multiple myeloma, or tumor metastases to bone marrow from any part of the body reduce the production of white blood cells. Also, cancer treatments -chemotherapy and radiotherapy- inhibit the bone marrow and reduce the production of white blood cells.
Infections: AIDS (HIV) and tuberculosis may cause leukopenia. Also, parvovirus inhibits bone marrow activity.
Hypersplenism (increased spleen activity): Normally, the spleen destroys blood cells at the end of their lifespan, or if they are abnormal. But in hypersplenism, it also destroys the normal blood cells leading to pancytopenia.
Autoimmune disorders (such as systemic lupus erythematosus and rheumatoid arthritis): These disorders make the immune system attack the own body tissues and cells, which may destroy the bone marrow and white blood cells.
Malnutrition: Low intake of some mineral (such as zinc and copper), vitamins (such as vitamin B12), and folic acid may cause leucopenia.
Medications: Some medication can affect bone marrow activity or the leucocytic function, such as:
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- Cyclosporine and cyclophosphamide (immune-suppressive drugs)
- Clozapine (antipsychotic)
- Bupropion (antidepressant)
- Interferons (used for the treatment of multiple sclerosis)
- Minocycline and penicillin (Antibiotics)
- Sodium valproate (antiepileptic)
- lamotrigine (anticonvulsant)
Symptoms of leukopenia
Leucopenia doesn’t exhibit specific symptoms. Its symptoms are due to the decreased power of the immune system and increased susceptibility to infection, which leads to symptoms, such as:
- Fever (temperature more than 38⁰c)
- Skin rash
- Chills
- Sore throat
- Malaise and fatigue
- Headache, toothache, and bony aches
Some organisms may enter the blood and release toxins, which lead to a serious condition called sepsis.
Treatment of leucopenia
In a patient with leucopenia, the treatment should aim to the following:
- Treatment of the cause
- Increase the production of white blood cells
- Prevention of infection and treatment of it if occurred
The doctor can achieve these goals in many ways, as follows:
Stoppage of the medication that caused leucopenia (such as chemotherapy, radiotherapy, and immune-suppressive drugs) and shifting the patient to safer drugs
Stoppage of anticancer therapy is the doctor’s decision because it depends on “which is the more dangerous cancer or leucopenia?”.
Treatment of the infection: either it was the cause or the result of leucopenia.
Growth factors, such as Granulocyte colony-stimulating factor: These factors stimulate the bone marrow to produce more white blood cells. Thus, they are helpful, especially if the cause is genetic, such as in aplastic anemia.
Diet rich in minerals and vitamins (such as fruits and vegetables) helps in raising the production of white blood cells, especially if the cause of leucopenia is malnutrition.
Some measure to reduce the possibility of infection in patients with leucopenia:
- Immunocompromised diet (low bacterial diet): This diet reduces the chance of infection in patients with weak immunity. The choice and preparation of this diet occur in a safe way to prevent its contamination with organisms. This diet includes foods, such as pasteurized milk and yogurt, well-cooked meats and eggs, and well-washed, canned or frozen fruits, and vegetables.
- Good hygiene practices, such as hand washing
- Avoid crowding and contact with sick people
- Be careful and avoid any activities that may lead to wound, even small bruises
- Avoid contact with animals
Either in leucocytosis or leucopenia, your doctor will ask you to do a complete picture (CBC) to know your white blood cell count. CBC also useful in the follow-up visits to determine the efficiency of the treatment plan.
Also, leucocytes in urine may indicate some health problems. Thus, we will discuss the leucocytes in the urine.
⇒ Now, let’s discuss leucocytes in urine (pyuria).
Leucocytes in urine (pyuria)
Normally, the level of white blood cells in urine is low, and its normal range is 0-5 WBC/HPF. But, if there is a high level of leucocytes in urine, this indicates that your body fights infection in the kidney or urinary tract (ureter, bladder, and urethra).
Causes of pyuria
1) Urinary tract infection (UTI) is the most common cause of high leucocytes in the urine, and it is more common in females.
2) Renal infections: infection may spread from the other parts of the body to the kidneys through the blood or spreads from the urinary tract.
3) Urinary obstruction: It may occur due to kidney stones or stones in the urinary tract, tumors, or trauma. It may lead to hematuria (blood in urine) or urinary tract infections.
4) Urine retention increases the chance of urinary tract infection.
Symptoms of pyuria
These symptoms depend on the cause and include:
- Fever
- Frequent urination and burning urination
- Cloudy and foul-smelling urine or hematuria
- Pelvic pain
- Nausea and vomiting
- Pain in one or both sides, back, or abdomen
Diagnosis of pyuria
If you have symptoms of urinary tract problems (infections or stones), your doctor will ask you to do a urine analysis. In urine analysis, your doctor will see the color, content (WBCs, RBCs, or bacteria), and concentration of urine. In pyuria, the urine is cloudy and contain leucocytes.
Also, the presence of nitrite or leukocyte esterase enzyme in the urine may be a sign of urinary tract infection, while proteinuria is a sign of renal disease.
The presence of nitrite in the urine is specific for certain types of bacteria, such as E.coli. Thus, we may have high leucocytes in urine without nitrite, but the presence of infection remains possible. In this case, your doctor will ask for more investigations to detect the cause of leucocyte in the urine (infection or other diseases?).
Treatment of high leucocytes in the urine
Treatment of high leucocytes in the urine depends on the treatment of the cause, as follows:
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- Antibiotic therapy for urinary tract infections
- Renal stones need removal by drinking more water if there are small, sound waves, or surgery if there are large.
- Other causes of obstruction may need specific treatment, such as chemotherapy for cancer or surgery.
- Some lifestyle changes may be useful, such as drinking more water, and evacuation of the bladder when it is full.
In some cases, we may see high leucocytes in the urine without the detection of bacteria, which known as sterile pyuria.
Causes of sterile pyuria
1) Sexually transmitted diseases, tuberculosis, and viral or fungal infection
2) Renal diseases and urinary tract stones
3) Renal and urinary tract tumors
4) Polycystic kidney disease
5) Prostatitis and interstitial cystitis
6) Some autoimmune diseases, such as systemic lupus erythematosus
7) Infection in any part of the body, such as pneumonia
8) Sepsis (presence of bacteria with their toxins in the blood)
» After understanding white blood cells (their function, number, production, their increase or decrease in blood, and their presence in urine), we will discuss leukemia.
What is leukemia, and how does it occur?
We defined leukemia as cancer of blood-forming tissues, which leads to an excessive increase in the production of blood cells, and in most cases, this increase affects white blood cells. The problem in leukemia is that these white blood cells are abnormal (called leukemia cells), and they can’t do what normal white blood cells do. Also, this increase in the production of white blood cells affects the production of red blood cells and platelets.
The net result is:
- Increased production of abnormal white blood cells (leukemia cells) that can’t protect the body, which reduces the immunity
- Reduced production of red blood cells and reduced oxygen supply to body tissues
- Reduced production of platelets, which increases the bleeding tendency
Causes of leukemia
We don’t know specific causes for leukemia, but there are some risk factors, such as:
- Smoking
- Positive family history of leukemia
- Genetic diseases, such as Down syndrome
- Cancer treatment, either radiotherapy or chemotherapy
- Exposure to ionizing radiation and benzene
- Blood diseases, such as Myelodysplastic Syndrome, which known as preleukemia
- Immune suppression as occurs with organ transplantation or immune-suppressive drugs
The clinical picture of leukemia
Manifestations of leukemia include:
› Bleeding tendency: Reduced platelet production makes the healing of wounds slow an difficult. Thus, leukemia patients bleed and bruise easily and have petechiae (red spots under the skin).
› Anemia: Reduced production of red blood cells impairs oxygen supply to body organs and tissues, and this causes symptoms like pale skin, weakness, fatigability, and difficulty breathing.
› Susceptibility to infections: Leukemia cells are unable to fight infections. Thus, leukemia patients are immunocompromised and susceptible to invasion by any organism.
› Other symptoms, such as fever, weight loss, night sweating, bone pain, painless enlarged lymph nodes, and enlarged liver and spleen
›» This cancer may spread to any part of the body, such as the brain, heart, lung, kidneys, and testes, and causes symptoms according to the involved organ.
Types of leukemia
Leukemia may be acute (sudden onset and rapid progression) or chronic (gradual onset and slow progression). Also, it may be myeloid or lymphocytic, according to the type of involved immature cells. Thus, we have four types of leukemia:
A) Acute lymphocytic leukemia (ALL): It is the most common type in children; it can also affect adults older than 50 years.
B) Chronic lymphocytic leukemia (CLL): It is the most common type in people older than 50 years, but it may affect young adults. It is rare in children. It is more common in males.
C) Acute myelogenous leukemia (AML): It affects children and adults, and it is the most common type in adults.
D) Chronic myelogenous leukemia (CML): It affects adults and rare in children. It represents 15% of leukemia cases in the United States.
Diagnosis of leukemia
After the physical examination, if your doctor suspects leukemia -due to causes, such as pale skin, enlarged liver and spleen, and swollen lymph nodes-, he will ask you to do some tests to confirm this diagnosis. These tests include:
• Complete blood picture (CBC): It determines the number and maturity of blood cells. In leukemia, there is a high number of abnormal white blood cells and low red blood cell count and platelet count.
• Bone marrow biopsy: It helps the doctor to identify the type of leukemia.
Treatment of leukemia
Treatment depends on the type of leukemia; some types progress slowly and don’t require immediate treatment, as in chronic types. Treatment choices include the following:
» Chemotherapy: it kills leukemia cells.
» Radiotherapy: it also kills leukemia cells.
» Target therapy: These medications kill the cancer cells and don’t affect the normal cells. Target therapy includes medications, such as imatinib (Gleevec), and nilotinib.
» Stem cell transplantation: This procedure aims to replacement of the diseased bone marrow with a healthy tissue that produces healthy blood cells. You will get high doses of chemotherapy to destroy the diseased bone marrow then you will receive hematopoietic stem cells to build a healthy bone marrow.
Prognosis of leukemia
Prognosis of leukemia depends on its type, patient’s age, the severity of anemia and thrombocytopenia, the spread of cancer, and the skills of treating doctors. The five-year survival rate depends on the type of leukemia.
If the child remains after five years, the chance of cancer return is low.