Bone marrow is a soft, fatty tissue that stores “stem cells”, which on maturing turns into blood cells. Stem cells are specialized cells that have the potential to grow and develop into various other types of cells. Thus, marrow is said to be the body’s blood factory where a single type of multi-protein stem cells divides and matures to give rise to different kinds of blood cells.
- Bone marrow is the production house of 12 different types of blood cells viz.
- Mast cell,
- Lymphoid dendritic,
- Myeloid dendritic,
- B – cell,
- T – cell
- NK cell.
- Each of these blood cells has their own specific functions.
- Red blood cells deliver oxygen throughout the body
- White blood cells fight pathogens in the blood
- Platelets help in clotting of blood
Cancer occurs when genetic mutations cause abnormal cells to divide and multiply in an uncontrolled way.
Unlike most Cancers, leukemic cells don’t belong to an organ and don’t result in the growth of a tumor. Instead, the uncontrolled cell growth takes place in the bone marrow. The leukemic cells are generally immature and do not carry out any physiological function of use to the body.
The word leukemia is derived from the Greek words “Leukos” meaning white and “aima” meaning blood.
Millions of blood cells are made every day and millions die at the end of their lifespan. There is a fine balance between the number of new blood cells and the number of worn out cells which gets phased out or die. Various factors help to maintain this balance. For example, certain hormones in the bloodstream and chemicals in the bone marrow called 'growth factors' help to regulate the number of blood cells. However, the abnormal blood cells do not follow this cycle; they continue to grow uncontrollably crowding out space in the blood, thereby impeding the function and growth of healthy blood cells.
Leukemias are grouped based on the rate of growth of Cancerous cells (acute or chronic) as well as the type of blood cell that is affected (lymphocytes or myelocytes). It is very important to know the type of leukemia as the outlook (prognosis) and treatment varies according to its types.
1. Lymphocytic or Myeloid Leukemia
The marrow synthesizes hematopoietic stem cells which may become a myeloid stem cell or a lymphoid stem cell. These are the precursor cells, also called “blasts”. These cells further give rise to several other cell types including monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes(RBC), dendritic cells and megacariocytes. Each myeloid cell eventually becomes a Red blood cell, a platelet or an infection-fighting macrophage. When Cancer occurs in these cells then it is calledmyeloid leukemia. Lymphoid cells develop into T, B and natural killer cells (NK cells). Cancer occurring in these cells is calledlymphocytic leukemia or lymphoblastic leukemia.
2. Acute or chronic
If Cancerous cells build up in the blasts cells rapidly filling the marrow and interfering with normal functions then it is called asacute leukemia. As Cancerous cells proliferate, the rate of normal blood cells production plunges. Acute leukemia is a fast-growing Cancer that usually gets worse quickly and so it demands fast and aggressive treatment. Normally, a person’s bone marrow contains 1 – 2 % of blast cells but in case of acute leukemia, the blast cell count increases over 20 %.
Chronic leukemia occurs in more mature lymphoid or myeloid cells. The irregular cells build up in the bone marrows over a period of years, interrupting the production of normal blood cells and spreading to other parts of the body.
These categories acute and chronic, lymphoid and myeloid are used to assign cases of leukemia to one of four subtypes
Acute lymphocytic leukemia (ALL) or Acute Lymphoblastic Leukemia
The build up of immature lymphoblasts is called acute lymphoblastic leukemia. In order to confirm if the affected cells are lymphoid cells, TdT is checked. TdT is a DNA polymerase that’s present only in the lymphoblasts. ALL is the most common type of leukemia accounting to almost 80% of all leukemia cases. It primarily occurs in young children between the ages of 1 and 4 but the prognosis is quite good and although it is rare among adults in whom the prognosis is generally poor.
ALL is further subtyped based on B cells or T cells.
- Precursor B-ALL: It is the most common subtype accounting for 84% of ALL. Chemotherapy is the most preferred treatment option to treat B-ALL.
- Precursor T-ALL: It accounts for almost 14% of all ALL cases. It occurs most often in teenagers.
Acute Myelogenous Leukemia (AML)
The build up of immature myeloid blasts is calledacute myeloid leukemia. To verify if the affected cells are myeloblasts, the presence of enzyme myeloperoxidase is checked. AML is more common among adult men between the ages of 50 and 60. Chemotherapy is the most preferred treatment option for this Cancer.
Chronic lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia (CLL) is a type of Cancer that starts fromlymphocytes in the bone marrow. This is most common leukemia among men over 55 years, although younger adults can get it as well. In CLL, the leukemia cells often build up slowly over time, and many people don't have any symptoms for initial few years. Though rarely able to be cured, most patients with CLL survive without treatment for years. On progression of the disease, they must be treated properly.
Chronic Myelogenous Leukemia (CML)
This Cancer occurs mostly in adults. A drug called imatinib is commonly used to treat CML.
Leukemia is one of the most deadly diseases which are very hard to treat. Almost 350282 people are diagnosed with leukemia each year around the globe.
A symptom is any abnormality shown by the body due to improper functioning of a single or group of organs. Since there are different types of leukemia so the symptoms of each type also differ.
Symptoms of Acute Leukemia :
Acute leukemia is an aggressive form and it develops very rapidly which causes some eminent symptom at an early stage.
Anemia – Due to the shortage of healthy red blood cells the patient usually suffers from anemia which causes weakness and fatigue. The patient may also suffer from labored respiration and pallor or paleness i.e. an unusual lightness of skin color as compared to normal complexion.
Blood clot - As the immature blast cells crowd out the platelets, which are crucial for blood clotting, the patient tends to bruise or bleed easily and heal slowly.
Affected immune system – In leukemia, the production of good white blood cells ceases to occur which leads to frequent infections, high temperature.
Pain in bones and joints
Symptoms of Chronic Leukemia
Chronic leukemia develops gradually over a long period without giving any signal at the early stages. However, it may become more active and more like acute leukemia after several years. The symptoms of chronic leukemia may include:
- swollen or enlarged lymph nodes, spleen and liver
- Anemia may also be a symptom of chronic leukemia
- fevers or night sweats
- discomfort or swelling in the abdomen,
- Unaccounted weight loss
- Red spots on the skin
However, in most cases the symptoms are not clear enough for suspicion of chronic leukemia; it can be confirmed only by a medical examination. So it is highly recommended visiting a doctor in case of experiencing any of the mentioned symptoms.
While the exact cause(s) of leukemia is not known, risk factors have been identified, which increases the chance that certain leukemia may develop. But these risk factors account for only a few cases. Some of the risk factors are:
- Radiation exposure
- Certain chemotherapy for Cancer
- Family history of leukemia. However, ALL does not appear to be inherited.
- Exposure to certain chemicals such as benzene.
- Viruses - HTLV-1 (human T-lymphotropic virus) and HIV (human immunodeficiency virus)
- Alkylating chemotherapy agents used in previous Cancers
- Maternal-fetal transmission (rare)
There is no known way to prevent most types of leukemia. Some types of leukemia may be prevented by avoiding high doses of radiation, exposure to the chemical benzene, smoking and other tobacco use, or certain types of chemotherapy used to treat other types of Cancer.
Staging of Cancer is essential for determining the location and spread of the Cancerous cells. Also, it is based on this stage that the complete prognosis of the patient can be planned. Usually, a numbered staging system is used to describe most types of Cancer/solid tumors and their spread throughout the body.
But for Acute lymphocytic leukemia, staging is done in a bit different way. Since the disease originates within the bone marrow and it is likely spread to other organs before detection, the staging method needs to take into account several other factors.
B-cell ALL staging
B lymphocytes that are produced and matured in the bone marrow are responsible for coordinating humoral immune responses and synthesizing antibodies against antigens. B – cell ALL can be staged as -
- Early pre-B AL: It accounts for 10 % of ALL Cancer.
- Common ALL: It accounts for 50 % of ALL Cancer.
- Pre-B ALL: 10% of ALL leukemia is reported to be of this type.
- Mature B-cell ALL: Also called Burkitt leukemia. It is a rare type and accounts for only 4% of cases.
T-cell ALL staging
T lymphocytes are produced in the bone marrow and they leave the bone marrow before maturation and move to the thymus. T cells play a central role in cell-mediated immunity. There are several subsets of T cells that have distinct functions. The different subsets of T cells include Helper, Cytotoxic, Memory, Regulatory, Natural killer and Gamma Delta T cells.
- Pre-T ALL: Approximately 5 to 10 percent of cases
- Mature T-cell ALL: Approximately 15 to 20 percent of cases
Acute myelogenous leukemia stages
As AML starts in the bone marrow and spreads really quickly so there is no specific staging for AML. AML is further classified using a cellular system and the treatment is planned based on this classification.
AML is classified into eight subtypes, M0 through M7, based on:
- The number of healthy blood cells
- The size and number of leukemia cells
- The changes that appear in the chromosomes of the leukemia cells
- Any other genetic abnormalities that have occurred
Chronic lymphocytic leukemia stages
CLL may be staged according to the following staging systems:
Rai staging system
- Stage 0 CLL: The levels of the lymphocytes are too high, usually more than 10,000 in one sample. Stage I CLL: The levels of lymphocytes is high and the lymph nodes are swollen.
- Stage II CLL: The number of lymphocytes is high and the liver or spleen might be swollen.
- Stage III CLL: The excess amount of lymphocytes begins to crowd out the red blood cells, resulting in anemia. The lymph nodes may be swollen and the liver or spleen may be larger than normal.
- Stage IV CLL: The levels of red blood cells and platelets drop below normal, causing anemia and thrombocytopenia. The lymph nodes may be swollen and the liver or spleen may be larger than normal.
Binet staging system
- Stage A: Lymph nodes may be swollen, but the Cancer is limited to fewer than three areas.
- Stage B: More than three areas of lymphoid tissues are swollen.
- Stage C: Either one or both of the blood disorders, anemia and thrombocytopenia, are present.
Chronic myeloid leukemia stages
There are three stages of CML.
- Chronic: This is the earliest phase of CML. The majority of CML patients are diagnosed during this phase as a result of mild symptoms, particularly fatigue.
- Accelerated: If CML has not responded to treatment well during the chronic phase, it becomes more aggressive, which can lead to the accelerated phase. At this point, symptoms may become
- more noticeable.
- Blastic: This is the most aggressive stage of chronic myeloid leukemia. Blastic refers to having more than 20 percent myeloblasts or lymphoblasts. Symptoms are similar to those of acute myeloid leukemia.
Mortality (death) rates for leukemia are higher in the elderly than in younger adults and children. In many cases, leukemia can be cured with treatments available today. The survival rate, however, cannot predict the outcome of any particular patient as the outlook varies largely on the basis of overall health condition, age and several other factors.
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:
|Type of Leukaemia||5 year survival rate|
As many types of leukemia do not show any early symptoms so it becomes a bit tricky to detect the disease at an early stage. However, being alert and not neglecting any minor signal regarding your health many a times proves to be life saviour. In case of any doubt about the disease, there are several tests that aid to clear the air.
Physical Examination: This is the first step of diagnosing leukemia. During the physical examination, the overall health record of the patient is taken into account and any sign of swollen glands is checked. If the person appears pale or complains about any of the mentioned symptoms then the doctor should suspect leukemia.
Routine Blood Test: Since leukemia is the Cancer of blood, a blood test gives a lot of information. Leukemia is suspected if a blood test shows large numbers of abnormal white blood cells and low numbers of normal white blood cells, red blood cells or platelets. If leukemia is detected then blood test is repeated after every three months for at least two years.
Bone Marrow Biopsy: A biopsy is done if leukemia is suspected and this test helps to identify the type of leukemia. In this procedure, a small amount of the Cancerous cell from the marrow is removed using a syringe and is observed under a microscope. Bone marrow biopsy may be uncomfortable and so sometimes the use of anesthesia is preferred.
Lymph Node Biopsy: In case of enlarged lymph, a lymph node biopsy is suggested. Tissues from the affected lymph are removed and examined under a microscope.
Imaging Tests: Several imaging tests like CT scan, X- ray, MRI may be performed to ascertain the spread of leukemia.
Chromosome testing: The genetic changes that occur in leukemia often involve chromosome changes, which can be seen under a microscope or using laboratory tests.
Lumbar puncture: This is done to check for leukemic cells in the spinal cord and brain. In this procedure, a fine needle is inserted between the bones in the lower back to take out a sample of fluid which are then evaluated under a microscope.
The treatment plan for leukemia depends largely on its type, age and health status of the patient. There are a number of different medical approaches to the treatment of leukemia.
Treatments for leukemia include chemotherapy (major treatment modality for leukemia), radiation therapy, biological therapy, targeted therapy, and 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.
Chemotherapy is the most preferred treatment in case of leukemia. It involves the use of drugs to kill the rapidly dividing cells. Chemotherapy may be taken orally 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.
- Biological therapy
Biological therapy is the use of substances of biological origin or synthetic versions of these substances to treat Cancer. Biological therapies may include antibodies, immunotherapy, tumor vaccines, or cytokines.
- Targeted therapy
Targeted therapies are drugs that interfere with one specific property or function of a Cancer cell, rather than acting to kill all rapidly growing cells indiscriminately. This means there is less damage to normal cells with targeted therapy than with chemotherapy. Targeted therapies may cause the target cell to cease growing rather than to die. Targeted Cancer therapies are also referred to as molecularly targeted drugs, molecularly targeted therapies, or precision medicines.
- Radiation therapy
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.
- 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.
Autologous stem cell transplantation refers to the situation in which the patient's own stem cells are removed and stored. The malignant cells are then targeted and destroyed. Once the malignant cells are completely destroyed then the patient’s own cells that were previously stored are reinfused.
- Supportive treatments
Because many of the treatments for leukemia deplete normal blood cells, increasing the risk of 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 medications or radiation therapy.
Types of supportive and preventive treatments that can be used for patients undergoing treatment for leukemia include the following:
- Vaccines against the flu or pneumonia
- Blood or platelet transfusions
- Anti-nausea medications
- Antibiotics or antiviral medications to treat or prevent infections
- 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])
- Red cell growth factors to stimulate red blood cell production (darbepoetin alfa [Aranesp] or epoetin alfa [Procrit])
- Intravenous injections of immunoglobulins to help fight infection Continue Reading
Acute leukemia can often be cured with proper treatment but chronic leukemia is unlikely to be cured with treatment. Treatments are often able to control the Cancer and manage symptoms in case of chronic leukemia.
Going for regular checkups and being attentive to even the slightest of health hazards may prove to be a life saving habit.