Cancer of the blood forming cells, in their early stages of development in the bone marrow. In simple terms it can be referred to as "Blood Cancer". Cancerous leukemia cells grow uncontrollably and abnormally in such a way so as to crowd the bone marrow and impair the normal production and development of other types of blood cells, as they not only compete for space in the bone marrow where they are produced but also for the nutrition they get from there.
If we talk about the blood, the very first thought that comes to our mind is of "Red coloured fluid". That is not all! Blood consists of various types of cells that have their origin from a type of cell, generally referred to as Hematopoietic stem cells(HSC). A kind of cell that eventually produce all the different types of cells of the blood and the immune system after undergoing various stages of development. HSC differentiates into either Myeloid stem cell or Lymphoid stem cell. These are blasts or immature cells and are relatively bigger in size and with less cytoplasm, as compared to their final mature and specialized forms. In normal bone marrow sample, percentage of blast cells usually lies between 1% to 2%. However, in a person with Acute Leukemia, the percentage of blast cells exceeds 20% in the bone marrow.
Myeloid stem cells undergo various stages of development to eventually form mature and specialized WBCs(other than Lymphocytes), RBCs, Megakaryocytes (Platelets are the cell fragments of Megakaryocytes) that can carry out specialized functions of delivery of oxygen, fighting infections and stopping or slowing down of bleeding.
Lymphoid stem cells undergo development leading to the formation of Lymphocytes such as B Lymphocytes or T Lymphocytes.
People are generally under the impression that since Leukemia is a type of cancer, it must be associated with the formation of a mass or tumor, however, that is necessarily not the case.
In Leukemia, HSCs differentiating into either Lymphoid or Myeloid stem cell, fail to differentiate or mature further to specialized mature blood cells. Their number, either Lympoid blast cells or myeloid blast cells, increases in the bone marrow depending upon which lineage is affected. These leukemic cells are not only stopped from achieving maturity but also divide exponentially competing with the normal blood cells for space, nutrition and growth factors. After all, bone marrow cavity is a closed restricted space. This leads to compromized space and nutrition for the normal cells leading to their impared production, growth and development and hampered function. RBCs, WBCs and platelets cannot perform their specialized functions eventually leading to the symptoms associated with Leukemia.
Once the build up of leukemia cells exceeds the capacity of bone marrow to handle, they start spilling into the blood leading to their increased number in peripheral blood as well. If there is an increase in Myeloblast, it is referred to as Acute Myeloid Leukemia whereas if there is an increase in Lymphoblast, it is referred to as Acute Myeloid Leukemia. It is important to know which type it is as they are two absolutely different entities and need distinct treatment.
There are different types of Leukemia depending upon the type of cell which is affected.White blood cells or Leukocytes are the most common blood cells to be affected and are generally referred to in Leukemia.
Types of Leukemia
The best treatment protocol and the prognosis is determined by the type of Leukemia.
Q 1. I would like to know about normal blood cells. Please explain.
A1 It is imperative to know about the normal functioning of the body with respect to formation and development of blood cells before proceeding further to know what happens in the diseased condition of leukemia, to gain better understanding.
Interestingly, all blood cells originate from blood stem cells(Hematopoietic Stem Cells). Different types of blood cells come from the blood stem cells which are mostly present in the bone marrow. Some are present in the preipheral blood as well and umbilical cord blood. HSCs have a unique capability to produce all the cells of blood and immune system. This process of blood cell formation from HSCs is controlled and well regulated i.e., the need of the blood cells determines the rate of their production by hematopoietic stem cells (the origin cell of all the blood cells). More requirement means more production, less need less production.
Types of blood cells that are produced can be summarized as below:
1. RBC or Red blood Cells, also referred to as Red blood corpuscles or Erythrocytes
They are the oxygen carriers in the body responsible for delivering oxygen to all the cells of the body. Low number of RBCs (Anemia)will result in inadequate supply of oxygen to the cells of the body leading the patient to feel tired, weak and short of breath.
2. WBC or White blood cells, also referred to as White blood corpuscles or Leucocytes
Soldiers in our body that help fight infections. Low count of WBCs will weaken your immune system and make you prone to develop infections.
3. Platelets or Thrombocytes
They make sure that blood clots effectively so as to prevent excessive bleeding. Having a low count of platelets, a condition referred to as Thrombocytopenia, will make the patient susceptible to excessive bleeding and easy bruising.
Under normal scenario, these cells get damaged or old, eventually leading to their death. New blood cells are formed to replenish the lost ones and this is done by the blood stem cells. This is achieved through two pathways. Blood stem cells (Hematopoietic stem cells) differentiate into Myeloid and Lymphoid stem cells. They are immature and are referred to as blasts. They undergo various stages of development and mature into specific mature blood cells that perform specialized function of carrying oxygen to all the tissues of the body, fighting infections and stop or slow down bleeding. Myeloid stem cells give rise to RBCs, platelets and Myeloblasts. Myeloblasts produce several types of WBCs grouped into " granulocytes" such as Neutrophils, Eosinophils and Basophils whereas Lymphoid stem cells give rise to Lymphoblasts (immature) that develops further to form other types of mature WBCs(Agranulocytes) such as Lymphocytes.
Q2 What happens in Leukemia?
A2. Leukemia is a cancer of the blood forming cells. It is characterized by uncontrolled and unregulated production of abnormal and immature (blast cells)cells in the bone marrow. As it is now known that hematopoietic stem cells present in the bone marrow, produce all types of blood cells. They first differentiate into two types namely Lymphoid stem cells and Myeloid stem cells. These two lineages of stem cells undergo various stages of development in order to produce mature blood cells that are well specialized in their structure and function.
Under normal circumstances, Myeloid stem cell develops and mature into Granulocytes( a type of WBC or Leukocytes), Monocytes, RBC(Red blood cells or Erythrocytes) and Megakaryocytes( Cell fragments of megakaryocytes are referred to as Platelets).
Lymphoid stem cells develop and mature into Lymphocytes (a type of WBC).
In Leukemia, either Lymphoid or Myeloid stem cell faces cell growth and development failure in their early stages of development. They start dividing uncontrollably to produce more of its own kind that are immature and abnormal, not capable of carrying out normal function as they would normally do if mature to form specialized blood cells.
Unlike normal cells, their production is not well controlled and well regulated. Moreover, they do not die when they get damaged or old. They keep dividing to form more cells like themselves competing for the space, nutrition and growth factors in the bone marrow. This eventually leads to compromized formation, development and function of all the normal blood cells such as WBC (that fight infection), RBC(Oxygen carrier to the body tissues) and Platelets(stops or slow down bleeding by formation of a clot).
Impairment of the normal blood cell production leads to the symptoms and signs associated with it such as low RBCs(Anemia), Low WBCs(Leukopenia, person loses ability to fight even the simplest of the infections) and low platelet count (Thrombocytopenia leading to bleeding disorders). Also, there are symptoms and signs due to accumulation f leukemic cells in the tissues depending upon their accumulation site.
Once the bone marrow is saturated with leukemic cells, they tend to spill over in the blood leading to their diffuse spread and this condition is referred to as Leukemia. Leukemia or blood cancer, as called in simple terms, in not just cancer of the WBCs, it may effect platelets and RBCs as well, however, they are rare whereas the cancer of the WBCs or leukocytes are more commonly found.
Q 3 What are the different types of Leukemia?
A3 Depending upon how fast Leukemia develops and advances, which in turn is determined by whether the abnormal leukemia cells are partially mature(more or less similar to normal WBCs) or totally immature (more or less similar to stem cells), Leukemia can be categorized as:
Acute leukemia: Develops and progresses rapidly. Patient may feel tired,is vulnerable to development of bruises and is also susceptible to infections. Acute leukemia is characterized by the production of Leukemia cells that are immature blood cells, normally referred to as blasts. Immature blood cells or blasts have the tendency to divide rapidly, which is out of control and that is how the Acute leukemia also progressively grows. However, unlike normal blasts cells, they do not stop dividing. The difference between Acute and Chronic leukemia lies in the pace of the onset of the disease and level of maturity of the Leukemic cells. Acute leukemia progresses and manifests itself in weeks whereas Chronic Leukemia may take even years to show up.
Secondly, although in both the cases the leukemic cells are immature blast cells. However, in Acute leukemia, the affected cells are completely immature and in their first stage of development from hematopoietic stem cells to mature specialized blood cells whereas in Chronic Leukemia, the affected leukemic cells are further down their path to maturation and development. i.e., they are more like mature specialized blood cells in appearance and function, though not normal. They not only divide rapidly but also live longer than normal cells would do.
Chronic Leukemia: Develops and progresses slowly, over years. Unlike Acute Leukemia, patient may not feel sick initially and most of the times Leukemia is accidentally discovered in a routine blood test. The leukemia cells are more mature as compared to that in Acute Leukemia, however, they are not fully normal and work well in this type either. They are not capable of fighting infection as normal WBCs would. As compared to Acute leukemia, they are hard to cure.
On the basis of the type of blast or immature cell affected(affected cell lineage-Lymphoid or Myeloid), the Leukemia can be further classified as:
Myeloid Leukemia: Leukemia that affects immature Myeloid cells. WBCs(other than Lymphocytes), RBCs, Platelets(Cell fragments of Megakaryocytes)
Lymphoid Leukemia: Leukemia that affects immature Lymphoid cells.
Most common types of Leukemia are:
Acute Myeloid Leukemia or AML : as the name suggests, this type of leukemia affects myeloid cells and progresses rapidly. It is a malignant or cancerous condition of the bone marrow in which the blood forming or hematopoietic cells are stopped in their early stages of development leading to the uncontrolled production of abnormal and immature(blasts) WBCs. It is also known by other alternate names such as Acute Myelogenous Leukemia, Acute Myelocytic Leukemia, Acute Granulocytic Leukemia or Acute Non Lymphocytic Leukemia.
AML begins in the bone marrow, at times, spreads rapidly to blood and eventually may spread to other organs as well such as liver, spleen, lymph nodes, brain, spinal cord. It is to be noted here that any cancer that initiates in some other organ and later develops in the bone marrow cannot be termed as Leukemia.
It usually affects older people, rarely seen before the age of 45 yrs. It is observed that it affects men slightly more than women.
Acute Lymphoblastic leukemia or ALL: Grows rapidly and affects Lymphoid cells. Cancer starts in the bone marrow where all blood cells are formed, also referred to as Acute Lymphocytic Leukemia. More commonly seen in children than in adults.
Chronic Myeloid Leukemia or CML: Grows slowly initially and it affects the myeloid cells. It is also referred to as Chronic Myelogenous Leukemia and constitutes around 10% of all the Leukemias.
Chronic Lymphoid Leukemia or CLL: This type of Leukemia affects Lymphoid cells(cells forming Lymphocytes, a type of WBC) and generally grows slowly. It is also referred to as Chronic Lymphocytic Leukemia. It commonly affects older adults.
Q4. What are the symptoms of Acute Myeloid leukemia(AML)?
A4 Symptoms can be categorized as below:
General Non Specific
Sudden loss of weight
Loss of appetite or anorexia
Also, there are symptoms that are caused due to low count of Red blood cells, normal white blood cells and platelets. Leukemia cells grow exponentially and hamper the formation of normal blood cells eventually leading to their low count.
Symptoms due to low red blood cells, often termed as Anemia
Shortness of breath
Low count of normal WBC makes the person prone to infections and infections are hard to treat. Leukemia cells are abnormal WBCs that do not have the capability to fight infections like the normal WBCs would.
Symptoms due to Low count of platelets
Frequent episodes of bleeding from the nose(Epistaxis)
Bleeding of gums
Symptoms due to high count of Leukemia cells
Leukemia cells are not only bigger in size as compared to the normal WBCs but are in huge numbers that make them clog the small blood vessels and blocking normal red cells and thereby the oxygen reaching the tissues. Symptoms produced are similar to that manifested in case of stroke.
Shortnes of breath
Loss of vision or blurred vision
Weakness in one side of the body
Q5 What are the treatment options available for Leukemia?
A5 The mainstay of treatment in Leukemia is Chemotherapy in its varied forms. "Chemo" means drugs or medicines and "therapy" refers to the treatment. Hence, treatment with chemicals or medicines that aim at killing rapidly dividing cells is referred to as Chemotherapy. Leukemia cells, as you now know, are rapidly dividing abnormal, immature white blood cells.
Chemotherapy is given in three different stages or phases commonly referred to as
Induction stage or phase, Initial phase lasting for around 4 weeks in order to kill the leukemia cells to the maximum possible. Bone marrow aspiration is done thereafter so as to check the effectiveness of the chemotherapy in achieving its goal of killing leukemia cells. Here we are aspiring to look at normal blood cells in the bone marrow. If it is achieved, the patient is said to be in the "Remission" , which can be defined as temporary decrease in the severity of the disease and its symptoms. Leukemia cells, even though not present in the bone marrow now,however, there is still a possibility of them coming back.
Consolidation stage or phase, that is marked by two things in mind. Firstly, to kill any further leukemia cells left behind during the first phase and secondly to protect the brain from Leukemia cells by hampering their journey to the brain. This target can be realized by administering chemotherapy in the fluid surrounding the brain, commonly referred to as CSF or Cerebro spinal fluid. This is usually done by injection into the CSF. You might be wondering why can the chemotherapy that is otherwise injected through blood, not sufficient to do so. The reason behind that is that the chemotherapy drugs administered through bood are not able to penetrate the brain.
Maintenance stage or Phase, generally lasts for around 2 to 3 years. Again same chemotherapy drugs are generally given in this phase also as were given during the first phase, however, in a lower dose with an aim to prevent the Leukemia from returning.
Besides chemotherapy as explained above, Radiation therapy may also be given, especially under the following circumstances such as:
The leukemia cells have already reached the brain.
Patient is vulnerable to get Leukemia cells into the brain
External beam radiation therapy may be given to the brain in order to kill those leukemia cells that have already reached the brain. The radiation therapy to the brain is not recommended for children below 5 yrs for their brain is still growing and administration of radiation therapy to them will impair normal growth and development of the brain.
Bone marrow transplant(BMT) is considered for those who are not responding to the above mentioned treatment such as Chemotherapy and Radiation therapy.
Q6 I have high blood count of White blood cells. Do I have Leukemia?
A6 High number of white blood cells does not necessarily means Leukemia. There are two more conditions which lead to high blood count of WBCs. Leukocytosis and Leukemoid reaction.
Leukocytsis, a condition characterized by high number of WBCs in the peripheral blood(in blood vessels) in response to inflammation, infection, stress and trauma. Normal WBC count in the peripheral blood is 4,000 to 11,000 WBC per microlitre of blood. However, in Leukocytosis, the WBCs mobilize from within the bone marrow, the factory and those adhering to the inner lining of the blood vessels to the peripheral blood in good numbers.
In Leukemoid reaction, the similar mobilization of WBCs take place in response to above situations of challenges to our immune system,however, in this case the numbers are very high as compared to Leukocytosis. The numbers of WBCs may be as high as upto 50,000 WBCs/micrilitre of blood.
To summarize, we can put it as mild to moderate increase in the WBCs count in the peripheral blood in response to the above conditions of inflammation,infection,stress and trauma, it can be referred to as Leukocytosis whereas when there is high increase in their numbers, it may be referred to as Leukemoid reaction.
They are both different from Leukemia associated increased WBCs count as Leukemia is a cancerous or malignant condition.
Q7 What is Myelodysplastic Syndrome?
A7 Myelodysplastic Syndrome(MDS) is a medical condition which is characterized by uncontrolled formation of abnormal and immature blast cells in the bone marrow. However, it cannot be referred to as Acute Myeloid Leukemia since the build up is less than 20%. Myelodysplastic syndrome may eventually progress to AML(Acute Myeloid Leukemia).
Literally, it means poor formation of normal blood cells in the bone marrow which subsequently results in the low blood cell count since their development is defective. Patients may experience infections and bleeding issues which may prove fatal or they can develop AML when the percentage of blast cells exceeds 20%. Such patients are diagnosed as patients with Acute Myeloid Leukemia with a history of Myelodyspastic Syndrome.
Q8 What is the difference between Leukemia and Lymphoma?
A8 Leukemia and Lymphoma are absolutely different entities.
Although, both the conditions are characterized by the malignant increase of blood forming cells(Hematopoietic Stem cells or precursor cells), which may be Lymphoid or Myeloid stem cells that fail to mature further into specialized and mature blood cells. Yet, the difference in cancerous blood forming cells's characteristics, their behaviour and way of spread into the body determines the type of blood cancer, whether Leukemia or Lymphoma.
In Leukemia, when the bone marrow gets saturated with the Leukemic cells, they tend to spill over in the blood and they are all over it(diffuse spread) whereas when they travel adhered to each other, encroach some body tissue or organ and form a mass, they are referred to as Lymphoma. They can initiate in one form, either Leukemia or Lymphoma, but can eventually transform to other type. The diagnosis depends on its presentation at the time of its detection.
Dr Ashok Kumar Vaid
MBBS, MD(General medicine), DM(Medical Oncology)
Chairman, Medical and Haemato-Oncology,
Cancer Institute,Medanta,The Medicity
Dr Anil Kumar Anand
MBBS, MD(Radiotherapy and Oncology)
Director Radiation Oncology
Max Super Speciality Hospital, Saket
Dr Satya Prakash Yadav
Director, Paediatric Hemato-Oncology and Bone Marrow Transplant
Medical and Hemato- Oncology, Cancer Institute,
Medanta The Medicity, Gurgaon, Delhi-NCR
Dr Sandeep K. Jain
MBBS, MD (Radiation Oncology)
Associate Director, Cancer Institute
Jaypee Hospital, Noida, Delhi-NCR
Dr Rahul Naithani
MBBS, MD(Pediatrics), DM(Clinical Hematology)
Senior Consultant, Bone Marrow/stem cell Transplantation and Clinical Hematology
Saket, New Delhi
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