Leukemia

What is Leukemia?

Leukemia is a term that encompasses several different types of blood cancers. The different types of leukemia are varied in their presentation, age of onset, risk factors and outlook.

Types of leukemia

There are four main types of leukemia:-

  • Acute lymphoblastic (lymphocytic) leukemia (ALL)
  • Acute myeloid (myelogenous) leukemia (AML)
  • Chronic lymphocytic leukemia (CLL)
  • Chronic myeloid (myelogenous) leukemia (CML).

Pathology

The basic tenet that is common in all leukemias includes the fact that they all begin in cells in the bone marrow. The bone marrow normally is responsible for generating the blood cells – red blood cells and white blood cells. One of the functions thus is to produce myeloid cells or white blood cells.

The growth and maturity of the bone marrow cells in these functions is tightly regulated by the cellular DNA. When the cell undergoes a change due to damage and changes in the DNA it becomes a leukemia cell and begins to proliferate uncontrollably.

Myeloid or myelogenous leukemia can begin in the cells that produce myeloid cells - red cells, white cells and platelets. Another type of cells affected is those that produce lymphocytes. Lymphocytic or lymphoblastic leukemia can arise in these cells.

Cause of leukemia

The exact cause of leukemias is unknown. As the bone marrow cells become leukemia they crowd the marrow and suppress other healthy cells. The rate of progression and replacement of normal bone marrow cells is different with each type of leukemia.

Who does leukemia affect?

Leukemia affects a large population of individuals worldwide. Around 274,930 people in the United States are living with, or in remission from, leukemia. In the UK, around 7,600 people are diagnosed each year with leukaemia. 

People can get leukemia at any age. Those over 60 are more at risk. The most common types in adults are AML and CLL.

ALL is the most common form of leukemia in children. For AML, specific risk factors have been found. This includes earlier exposure to chemotherapy, Down’s syndrome and other genetic disorders, exposure to benzene and other chemicals, exposure to radiation therapy etc.

Signs and symptoms of leukemia

There are several signs and symptoms of leukemia that are common to all types. Specific blood tests and bone marrow tests are needed to make a diagnosis. In acute leukemias common symptoms include:

  • lack of energy
  • fatigue
  • anemia
  • prolonged fever
  • night sweats
  • unexplained bruises
  • prolonged bleeding tendencies
  • propensity to catch infections etc.

People with CLL or CML may not have any symptoms. CLL may manifest with enlarged lymph nodes in the neck, armpit or groin.

Diagnosis, treatment and outcome

Treatment, diagnosis and approach to each type of leukemia is different. ALL and AML (acute leukemias) are each composed of young cells, known as lymphoblasts or myeloblasts. Routine blood tests with complete blood counts help in diagnosis.

Bone marrow tests (aspiration and biopsy) are often done to confirm the diagnosis and to look for chromosome abnormalities. These tests identify the leukemia cell-type. Each main type of leukemia also has different subtypes.

Acute leukemias progress rapidly without treatment. CLL and CML, on the other hand have few or no blast cells. CLL and CML often progress slowly compared to acute leukemias without treatment. Today, more and more leukemia patients are in complete remission at least five years after treatment. The aim of therapy is to achieve complete remission.

Treatment for patients with acute leukemia may include chemotherapy, stem cell transplantation etc. Those with ALL and AML, start with treatment immediately after diagnosis using chemotherapy. The first part of treatment is called induction therapy. Treatment is given after remission. This is called the consolidation (intensification) therapy and maintenance therapy. This part of treatment may include chemotherapy with or without stem cell transplantation (sometimes called bone marrow transplantation).

Patients with CML need treatment soon after diagnosis. The drugs that can be used include imatinib mesylate (Gleevec®), dasatinib (Sprycel®) or nilotinib (Tasigna®). These are oral drugs that target the cancer specifically. Allogeneic stem cell transplantation is another treatment option for CML.

CLL usually progresses slowly without treatment and some CLL patients do not need treatment for long periods of time after diagnosis. Patients who need treatment may receive chemotherapy or monoclonal antibody therapy in combination. Allogeneic stem cell transplantation is a treatment option in some subgroups of patients.

Leukemia Causes

How does leukemia develop?

The human body consists of trillions of cells. Each cell contains chromosomes. A gene is the component of chromosomes that carry genetic messages. The gene is made up of a strand of Deoxyribonuclieic acid (DNA). Damage to the DNA is responsible for the initiation of cancer. The damage may be in the form of shifting or rearrangement of chromosomal bits and segments.

Normally the DNA is capable of correcting its damage on its own. When this self-correcting measure fails, cancer develops. Damage to the DNA of white blood cells can lead to onset of leukemia. A single type of leukemia may contain several genetic abnormalities.

Acute Leukemia, especially of the myeloid variety (AML), results from a defect in the proliferation and maturation of white blood cells within the bone marrow. These immature leukocytes fail to develop into mature leukocytes. Leukemia is suspected when there is an excess of immature leukocytes in blood or bone marrow.

Chronic leukemia affects adults more commonly than acute leukemia. They may have a slower progress than acute leukemias. This is the benign phase that is followed by a ‘blast’ phase where the disease progress is vastly accelerated. As in acute leukemia, there may be chromosomal abnormalities in chronic myeloid leukemia (CML).These changes may lead to specific alterations in certain proteins and enzymes in the body. Commonly an enzyme called tyrosine kinase shows increased activity in CML due to the Philadelphia chromosome (a chromosomal abnormality).

Causes and risk Factors

The exact cause of leukemia is unknown but several risk factors may raise the chance of getting leukemias. These include familial and genetic risks as well as environmental and lifestyle factors.

Familial and genetic factors

Genetic abnormalities play an important role only for a small proportion of cases of leukemias. In most of the cases there is an interaction with faulty genes and DNA damage with environmental and lifestyle factors to bring about risk of leukemia.

Some genetic abnormalities have been associated with leukemias directly. These include Philadelphia chromosome and its association with CML. Klinefelter syndrome, Down syndrome, Bloom syndrome ataxia, telangiectasia and Fanconi syndrome are chromosomal disorders leading to predisposition of leukemia.

First-degree relatives including parents, siblings, or direct offspring with chronic leukemia have a two to four times increased risk for this cancer.

Age

Most (70%) of the leukemias are seen in patients over the age of 50.  Patients diagnosed with AML, CML and CLL are usually adults and the elderly. ALL, however is more common in early childhood.

It is suggested that the chromosomes of white blood cells of the elderly are fragile and more prone to DNA damage and changes that may lead to leukemia. With age, there is a reduced ability of the DNA to repair itself and protect itself against damage. There could also be free radical damage to the DNA in the elderly.

Lifestyle factors

This includes factors like smoking and dietary factors. A diet rich in fruits and vegetables and other antioxidants can help prevent against DNA damage caused by free radicals and thus may have a role in reducing the risk of call cancers including leukemias. Increased cigarette smoking is associated with increased risk of leukemia. Cigarettes contain agents such as benzene and other chemicals that have been linked to leukemias.

Environmental factors

Studies have shown that several environmental and past exposures may raise the risk of leukemias. Previous exposure to chemotherapy and radiation raises the risk of leukemias.

Alkylating agents, used to treat other cancers, significantly increases the risk of leukemia. In patients treated with alkylating agents for various cancers, there is an increased likelihood of development of leukemia.

Ionizing radiation used for other cancers raises risk of AML, ALL, and CML but not for CLL. Those exposed to radiation are also at risk of leukemias. Studies show that half of all cases of leukemia diagnosed between 1950 and 1987 were attributable to radiation in Hiroshima and Nagasaki after the atomic bomb explosion.

Certain chemicals like benzene raise the risk of leukemias. Benzene is used as a solvent in leather, printing and petrochemical industries. Benzene exposure occurs at the workplace or by environmental sources such as tobacco smoking.

Acute leukemia, especially those affecting T cells, may be caused by exposure to the human T cell leukemia virus (HTLV). This virus has proteins that attaches to the proteins in the lymphocytes and causes abnormalities in their growth leading to cancer.