Leukemia - A Power Point Collection

**trimurtulu** · 01-18-2009, 10:01 PM

Leukemia - A Power Point Collection

The term ‘leukaemia’ actually describes a group of cancers involving an excess of white blood cells.

In leukaemia, normal control mechanisms in the blood break down and the bone marrow starts to produce large numbers of abnormal white blood cells, disrupting production of normal blood cells and affecting the vital functions that these blood cells carry out.

Leukaemia can be classified as either lymphoid or myeloid, denoting the type of white blood cell affected. It is also categorised as either acute or chronic, reflecting the speed of progression.

Acute leukaemias

Almost all childhood leukaemias are of the acute form, meaning that they progress rapidly.

• Acute lymphoblastic (lymphoid) leukaemia (ALL) accounts for more than 80% of cases of childhood leukaemia. It is the only form of leukaemia – and one of the few forms of cancer – that is more common in children than in adults.

• Acute myeloid leukaemia (AML) accounts for most of the remaining cases.

Chronic leukaemias

Chronic leukaemias, which progress slowly, are very rare in childhood.

• Chronic myeloid leukaemia (CML) accounts for less than 3% of childhood leukaemias (less than 15 children per year in the UK).

• Chronic lymphoblastic leukaemia is unheard of in children

What causes leukaemia?

The “two-hit hypothesis” proposes that initiating events take place whilst the child is still in the womb, with a second ‘hit’ later in life triggering the development of full-blown leukaemia.
Childhood leukaemia is not a hereditary disease so children do not inherit the disease from their parents. However, there are a number of different genetic mutations linked to the disease and scientists have shown that these mutations are already present when the child is born.
Not all children born with the mutations will develop leukaemia. For example, the ‘TEL-AML1’ mutation is present in around 1% of new born babies but less than 1% of those born with this mutation will actually develop leukaemia.
This suggests that whilst the development of childhood leukaemia is initiated when the child is still in the womb some other factor may trigger the development of full-blown leukaemia later in life. This is known as the “two-hit hypothesis”.

Environmental and lifestyle factors
The incidence of childhood leukaemia increased steadily throughout the twentieth century at a rate of approximately 1% per year.

This suggests that factors linked with our modern lifestyle may have increased the risk of our children developing leukaemia. These factors may exert their effect either before or after birth.

Because of the relatively low number of children developing leukaemia each year and of the multi-factorial nature of the disease, it is often very difficult to establish associations with particular factors.

Studies have reported associations between childhood leukaemia and a number of environmental and lifestyle factors, with varying degrees of certainty.

Some of these factors – such as exposure to ionising radiation or certain chemicals – have been linked with an increased risk of developing childhood leukaemia.

Other factors have been linked with a decreased risk of developing the disease. Breast-feeding is a factor that has been shown to have a protective effect.

Why is it important to research the causes?
The increased incidence of childhood leukaemia suggests that there is something about our modern lifestyle which has raised the risk of our children developing the disease.

If we can understand what elements of our changing lifestyle are putting our children in danger, we may be able to take steps to reverse the increasing incidence.

Improving our understanding of the causes of childhood leukaemia and the mechanisms by which it develops may also give us a better insight into ways of treating the disease.

Treatments

Great advances in treatment and care mean that four out of five children diagnosed with leukaemia are now cured.

Acute forms of leukaemia are rapidly fatal without effective treatment. Fifty years ago almost all children diagnosed with acute leukaemia died, often within weeks.

Advances in treatment and care means that today four out of five children survive. However we still have a long way to go.

There are certain forms of the disease which still evade successful treatment.

Many of the survivors are left with serious, lasting side-effects from the powerful treatments which are used to save their lives.

Treatment usually begins within a few days of diagnosis. All children diagnosed in the UK are treated at specialist paediatric referral centres which can be some distance from home.

The aim of treatment is to achieve a state called remission where almost all leukaemia cells have been killed, allowing production of normal blood cells to resume. Further treatment is given to eradicate the disease completely and achieve a cure.

The child’s doctor will follow a treatment protocol which will vary depending on the form of leukaemia as well as certain risk factors.

Treating acute lymphoblastic leukaemia (ALL)
Chemotherapy is the main treatment for childhood ALL. Usually a combination of chemotherapy drugs is given according to a treatment plan.

The treatment, which is mostly given on an outpatient basis, is given in several ‘blocks’:

Block I: Remission induction
The aim of the first few weeks of treatment is to return both the blood and the bone marrow to normal function – this is called achieving a remission.

This intensive phase of treatment involves the use of several drugs in combination to clear all detectable leukaemia cells from the blood and the bone marrow.

Children will spend part of this stage of treatment as inpatients because of the risks of infection and haemorrhage.

Block II: Central nervous system (CNS) directed therapy
Some leukaemia cells may cross the barrier into the cerebro-spinal fluid (CSF) which surrounds the brain and spinal cord. Unfortunately the anti-leukaemia drugs do not penetrate this barrier very well and so it is necessary to inject drugs directly into the spinal fluid to prevent leukaemia cells from surviving in this site. This is called an intrathecal injection.

Radiotherapy may also be used to target leukaemia cells in the CNS – but only if the patient has evidence of CNS disease at the time of diagnosis.

Block III: Delayed intensification therapy
The disappearance of leukaemia cells from the blood and the bone marrow does not mean that all the leukaemia cells in the body have been killed. Therefore it is necessary to give further blocks of treatment in order to maintain the remission.

Standard treatment involves two courses of powerful drugs given at roughly four and eight months from diagnosis. The drugs will affect the child’s bone marrow and its ability to produce blood cells, leading to a fall in their blood count and associated problems such as infection and bleeding. Children may need to be admitted to hospital during this period of their treatment.

Block IV: Maintenance therapy
This phase of extended low-dose oral chemotherapy is unique to the treatment of ALL. Without this phase of treatment, which lasts 14 months for girls and 26 months for boys, there is an increased risk of relapse.

Treatment during this stage involves taking daily tablets and having monthly injections of chemotherapy drugs.

The maintenance stage takes the total treatment duration to two years for girls and three years for boys. It is carried out as an outpatient, with treatment provided on a ‘shared care’ basis with a partnership between the specialist treatment centre and the child’s local hospital.

Although the specialist centre retains overall responsibility, much of the care is provided by the local hospital. This has major benefits for the child and family – it avoids the need for long journeys and reduces the disruption to family life and the child’s education. The child should be able to resume normal activities during this time.

Treating acute myeloid leukaemia (AML)
Children with AML must be admitted to hospital for most of their treatment because of the high level of supportive care required to combat the side-effects of treatment.

There are two phases in the treatment of childhood AML - remission induction and post-remission treatment. The total duration of treatment is much shorter than for ALL as extended maintenance therapy is not required.

Phase I: Remission induction
The first phase involves using intensive treatment to destroy as many of the leukaemia cells as possible.

Remission induction usually includes two blocks of a combination of chemotherapy drugs in high doses given over a few days at intervals of one or two weeks.

The intensity of treatment needed to achieve complete remission causes severe bone marrow suppression, leaving the child prone to bleeding or infection.

Although there are gaps of either one or two weeks between blocks of therapy, children need supportive care to combat these risks and will therefore need to stay in hospital during this time.

As for ALL a potential problem in the treatment of AML is central nervous system (CNS) relapse. Leukaemia cells can enter the cerebro-spinal fluid (CSF) which surrounds the brain and spinal cord and it is necessary for drugs to be injected directly into the spinal fluid to kill any leukaemia cells which may be remain. Radiotherapy may also be required particularly if leukaemia cells are detected in the CSF at the time of diagnosis.

Phase II: Post-remission treatment (also known as consolidation)
Consolidation aims to destroy any remaining leukaemia cells and to stop the disease from returning. This phase usually involves two or three more blocks of chemotherapy.

Treating chronic myeloid leukaemia (CML)
Unlike ALL and AML, childhood CML cannot be cured by any type of chemotherapy at present.

Chronic myeloid leukaemia is a form of leukaemia that progresses slowly during its initial phase. This chronic phase can last six years or more before undergoing a transformation to a second ‘accelerated’ stage, which lasts three to nine months.

In the third and final ‘blast’ stage, the disease resembles acute leukaemia and is usually fatal within three to six months.

No form of chemotherapy is currently thought to cure CML although a new drug called imatinib can eliminate easily detectable signs of leukaemia from the blood, prolonging the chronic phase of the disease and delaying transformation to the accelerated stage.

The only treatment that can cure childhood CML is a stem cell transplant using cells from a matched donor.