Leukaemia

There are three types of blood cells circulating in the blood, the red blood cells, platelets and white blood cells. They are all produced by the stem cells in the bone marrow. Normally, bone marrow stem cells will multiply and grow into mature blood cells. When blood cells are mature, they will leave the bone marrow and circulate in the peripheral blood. With leukaemia, there is an abnormal growth or accumulation of white blood cells in both the bone marrow and peripheral blood, leading to elevation of white blood cell count.

There are many types of types of leukaemia and treatment varies for different types. Leukaemia is classified into acute leukaemia and chronic leukaemia. They can be further classified according to the cell types:

• acute myeloid leukaemia (AML): a cancer of myeloid blood cells. It is the most common type of leukaemia, mostly in older adults.
  
• acute lymphoblastic leukaemia (ALL): a cancer of the immature lymphoid cell. It occurs more often in children and the most common leukaemia in children. 
  
• chronic myeloid leukaemia (CML): a cancer of myeloid cells associated with presence of Philadelphia chromosome and more common in adults.
  
• chronic lymphocytic leukaemia (CLL): which is a cancer of mature lymphoid cells. It occurs mostly in older individuals (>60 years old). It rarely occurs in children.

Acute leukaemia is a fast- growing cancer of blood and bone marrow. The affected bone marrow makes lots of abnormal immature white blood cells (known as “blast cells”). These abnormal immature white blood cells are leukaemic cells. The leukaemic cells grow quickly in the bone marrow and affects healthy blood cells production, leading to symptoms of aneamia (tiredness) and low platelets (easy or excessive bleeding). Patient is more vulnerable to infection because of insufficient normal white blood cells to fight against bacteria and viruses.

In contrast to acute leukaemia, chronic leukaemia is slow growing cancer that develops over a longer period time. Majority of the patients have no or mild symptoms initially until the disease become more advanced stages or when the while blood cells is dangerously high.

CML is slow growing bone marrow cancer caused by a characteristic chromosomal abnormality in the bone marrow stem cells and leukaemia cells. In these cells, part of chromosome 9 switches places with part of chromosome 22. This abnormal chromosome is called Philadelphia chromosome and is also the hallmark of CML. It signals the marrow to make lots of white blood cells, resulting in CML. CML has three phases, the chronic phase, accelerated phase and blast phase. Most, but not all patients, are diagnosed in chronic phase.

In CLL, too many blood stem cells turn into mature but poorly functioning abnormal B-lymphocytes (the leukaemic cells) in marrow and blood. These abnormal B-lymphocytes live much longer than normal  and build-up in the blood. They are not good in fighting against infections. These result in infection, anaemia and easy bleeding. Some CLL are associated with features of auto-immune diseases.  

The exact cause for leukaemia remains poorly understood. Leukaemia is thought to begin with one abnormal cell in the marrow, in which, the certain vital genes that control how cell multiply, grow, and die have been altered. Yet, the reason why the cell becomes abnormal is largely unknown. In fact, most patients do have any specific cause identified.

The following risk factors may increase the risk of getting leukaemia:

• Exposure to excessive radiation (e.g. prior radiotherapy and atomic bomb survivors)
  
• Exposure to toxic chemicals (e.g. benzene and prior chemotherapy treatment)
  
• Certain genetic disease (e.g. Down syndrome)
   
  

Acute leukaemia is fast-growing cancer. Typically, acute leukaemia develop quite quickly and rapidly become worse over a few weeks or so. Patient becomes generally unwell, rundown with symptoms of anaemia, easy bleeding, and infections.

Chronic leukaemia does not usually cause any symptoms at initial stage. It is usually found during routine blood tests. Some CLL patients are diagnosed when enlarged of lymph nodes are discovered during routine examination by doctor.

If you have the following symptoms, you should consult your doctor as soon as possible:

• Fever and frequent infections
  
• Feeling tired (from anaemia)

• Easy or excessive bleeding
  
• Painless swelling of lymph nodes in neck, armpits or groins
  
• Unexplained weight loss

If leukaemia is suspected from the history and physical examination, your doctor will arrange the following tests for you:

Complete Blood Picture: A blood sample is collected and examined for the quantity of red cells, platelets, white cells and presence of leukaemic cells.

Bone marrow aspiration and biopsy: Bone marrow aspiration and biopsy is a procedure to collect bone marrow blood and small piece of bone by inserting a special needle into patient’s hip bone. The procedure is generally performed under local anaethesia at bedside and takes about 30 minutes. The bone marrow sample obtained will be evaluated by pathologist to determine the presence of leukaemia cells, leukaeima diagnosis and classification.

Chromosome or molecular testing: These are special testing performed in peripheral blood and bone marrow blood samples to detect abnormal changes in chromosome, DNA or tumor markers that are associated with presence of leukaemia.

The doctor may also perform some additional testing to determine the general health of the patients and the extent of the disease.

Treatment of leukaemia varies considerably depending on the types and stages of the leukaemia.

Acute myeloid and lymphoblastic leukaemia

With acute leukaemia, doctor will usually begin treatment right away with repeated cycles of chemotherapy. The initial course of chemotherapy (induction chemotherapy) is very intense and is carried out in hospital. The drugs used and treatment plan are different between AML and ALL. The goal of induction chemotherapy is to eradicate the leukaemia cells in bone marrow and bring the disease in remission. The remission rate for AML is about 50% -70% in adults. In ALL, the remission rate for children is more than 95% and about 75%-89% in adults. All-trans retinoic acid (ATRA), an oral medication, will be used together with chemotherapy if patient has the special subtype of AML called acute promyelocytic leukaemia. During the course of treatment, patients will also receive blood transfusion and other supportive treatment to minimize risks of serious complications such as major bleeding and life-threatening infections.

Once remission is achieved, patient will receive further courses of chemotherapy (consolidation chemotherapy) because acute leukaemia as risk of relapse. Patient with ALL will also receive radiation therapy to the brain and longer period of low-dose oral chemotherapy (maintenance chemotherapy). Doctor may consider stem cell transplantation early in the course of treatment for patient who has high risk disease and matched donors.

Chronic myeloid leukaemia

Treatment options for CML include imatinib (or its alternatives: dasatinib, nilotinib), interferon, hydroxyurea, and allogeneic stem cell transplantation. For most CML patients, imatinib is the standard first line treatment. It stops leukaemic cell production by blocking a specific enzyme called tyrosine kinase in the marrow cell and prevent the development of accelerated phase and blast phase. Most CML patients respond well to imatinib therapy with minimal side effects. Patients who responded to therapy are required to continue the drug indefinitely and are able to continue a normal life. Because of the favorable treatment results of imatinib, imatinib has largely replaced the use of interferon and other therapy. The need for allogeneic stem cell transplantation has also substantially reduced nowadays.

Chronic lymphocytic leukaemia

CLL is generally a slowly growing disease. It usually occurs in older patients. Treatment therefore depends on age of the patient, presence of symptoms, disease stage and general health of the patient.

Most patients, particularly those with early stage disease, are asymptomatic at diagnosis and do not need therapy. Doctor may recommend observation (watchful waiting) initially by regular check-up to carefully monitor patient’s health and disease progress. Treatment usually starts when the disease has progressed or begins to have troublesome symptoms. At this stage, treatment can be chemotherapy or use of monoclonal antibody. Patient may also require blood transfusion or supportive treatment for complications such as infection or anaemia.

Diagnosis of leukaemia is often devastating for both the patient and his/her family. While it is difficult to avoid focusing on the treatment relating complications and possibility of dying, it is important for patient and his/her family to remember that many patients can have good control and cure with treatment available today. 

There are some practical support that may help you and your family fight the leukaemia in a positive way:

Take medicines regularly: Patient should know the dosage and side effects of various medications (chemotherapy drugs or antibiotics). Follow the instruction given by your doctor. Do not stop medication on your own.

Eat well and sleep well: Eating well is always important especially when you are coping with extra physical demand by the leukaemia and its treatment. It is important to take a balanced diet that provides you energy and good nutritional values. Food should be well cooked. Regular exercise, appropriate rest and sleep well also help. Patients with CML or CLL are encouraged to live a normal life style as before.

Household and personal hygiene: Patients with acute leukaemia or advanced chronic leukaemia are vulnerable to infection. You should pay attention on household and personal hygiene. Rooms, clothing and household appliances should be tidies and kept clean. Avoid going crowded or public places and contact with friends who are sick and unwell with infection. Wear masks when going outdoor.

Talk to someone else: Living with leukaemia can be enormously stressful. Do talk to your family, friends, your doctor, nurses or someone you trust about your feelings during the course of treatment. You will find emotional support and feel much better by just talking to them. If necessary, your doctor would provide you more support and counseling through psychologist, chaplain service and patient support group.