What are the Investigations done to Diagnose Chronic Myeloid Leukaemia

The physician will do a series of investigations starting from the simplest.

·         Full blood count – The results we are looking for are almost equal to those in acute leukaemia, which I have described in one of my previous posts. Simply there will be raised white cell count and low or normal platelet count.

·         Blood film – this is done to identify neutrophilia and myeloid precursors. This will also reveal occasional blasts, increased basophils and eosinophils.

·         Bone marrow aspirate – This is a very specific investigation that is capable of giving very accurate information about the disease. It may show increased cells and myeloid precursors in the bone marrow. The same specimen can be used to look for t(9;22) Philadelphia chromosomal abnormality, which is specific to chronic myeloid leukaemia.

·         FISH – FISH stands for fluorescien in situ hybridization. This technique can detect cytogenetic abnormalities of the cells. This is also used after the therapy to finds out the response to treatment.  

·         Leukocyte alkaline phosphatase – this is an enzyme which usually reduce in amount when some one has leukaemia.

References : Kumar P and Clark M, 2009. Clinical Medicine. 7th ed.

Clinical Features of Chronic Myeloid Leukaemia

Since all chronic leukaemias evolve slowly with time, the patient may not have any symptoms at all. But some may have some of the following symptoms.

·         Symptoms of anaemia – easy fatigability, low exercise tolerance are features of anaemia.

·         Abdominal discomfort – Chronic Myeloid leukaemic patients can develop massive enlargement of the spleen. This leads to abdominal discomfort due to its heavy weight.

·         Weight loss – weight loss is a feature of any chronic illness.

·         Fever and sweating – as I describes in my initial posts there is a high metabolic processes going on in leukaemic tissues. This high metabolic activity creates a lot of energy which is released as heat. As a result the patient begins to have fever and sweating.

·         Headache – this is mainly due to hyperleukocytosis.

·         Symptoms of thrombocytopenia -these symptoms include bleeding, bruising and priapism.

Other than above mentions symptoms of chronic leukaemia, the following signs can also be found if examines carefully.

·         Pallor – look carefully under the lower eyelid, if it is pale in colour then you have developed anaemia. But, don’t jump in to the conclusion that you have leukaemia just because you are pale. Pallor can also be a feature of thousands of other diseases.

·         Palpate the abdomen starting from the right lower part of the abdomen and then gradually palpate lightly towards the left upper part of the abdomen. If you something firm in this path, it is the enlarged spleen.

·         Lymphadenopathy – this is enlarged lymph nodes in the body.

·         There will be retinal haemorrhages, but it needs a special equipment to visualize retinal haemorrhages.    

References : Kumar P and Clark M, 2009. Clinical Medicine. 7th ed.

 

Outcome of Acute Lymphoblastic Leukaemia

The outcome of acute lymphoblastic leukaemia depends on several factors.

·         Age – older people have laser survival rates.
·         White Blood Cell Count – Higher the initial number of white cells, high the chances of recurrences in the central nervous system.
·         Immunophenotype – B cell is associated with poor prognosis.
          Pre B cell form has a better prognosis than B cell form.
         T cell form has better outcome than the both mentioned above 
·         Cytogenetic aberrations – patients with t(9;22) or t(4;11) are more prone to have poor outcome.
·         Time to response – high the time taken to achieve complete remission, higher the chances of failure.
 

It is good news to know that children with acute lymphoblastic leukaemia have a better outcome. There is 100% complete remission rate.  But if recurrence occurs the outcome will be very bad.

References : Kumar P and Clark M, 2009. Clinical Medicine. 7th ed.

Treatment of Acute Lymphoblastic Leukaemia

As in all leukaemic treatment the first thing in acute lymphoblastic leukaemia is also remission induction. This treatment method is called combination chemotherapy. The following drugs are used in this treatment method.

·         Vincristine

·         A glucocorticoid – dexamethasone, prednisolone

·         An anthracycline - Daunorubicin

·         Asparaginse (crisantaspase)

When the above therapy succeed in achieving complete remission there are some other actions that has to be taken. They are,

·         Consolidation - The second step is consolidation after a successful remission is achieved. The patients will be a number of cytotoxic drugs several times. One such drug is Methotrexate, which is used in high dosage.

·         Allogenic transplantation - In some patients who are at high risk allogenic transplantation is done when they achieve the first remission.

·         Intrathecal Chemotherapy - May have to be continued upto two years depending on the risk. This is under platelet cover and with high doses of systemic Cytosine arabinoside or methtraxate.

·         Cranial irradiation – This now only done for those who are at high risk.

·         Maintanace therapy – Continuation of treatment with methotrexate and mercaptopurine for up to 2 years. A white cell count of 3×10⁹/L is targeted.    


References : Kumar P and Clark M, 2009. Clinical Medicine. 7th ed.

Treatment of Acute Myeloid Leukaemia

This is one kind of the acute leukaemias.  When we find out that we have some kind of disease the, the first thing that comes in to our mind is “is it curable?’ So the leukaemic patients also think the same way. For diseases such as cough and cold, the answer is very straight forward and easy, but leukaemia is not such simple disease, so we cannot give a simple straight forward answer.

Leukaemia is a complex disease and as a result of that complexity, there is a wide variety of presentation of the disease. Not only that, the response to treatment also differs from patient to patient.

According to the previous data, acute myeloid leukaemia can be curable in some patients. The next question is ‘who are the people that can be cured?” Well “yes” but for some. Generally adults who are under 60 years old are treated with curative intent, but not all. Those who have other co morbidities (other significant illnesses) are not treated with curative intent.

Out of those who are treated, some may fail to eliminate the disease entirely. The physician categorizes the disease as low risk and high risk. This is done according to the cytological (the cellular) pattern. So if you belong to the low risk group, you will be treated with “Moderately intensive combination chemotherapy”. This always includes an anthracycline. Examples of anthracycline include daunorubicin and cytosine arabinose.  Then at least 4 cycles of treatment will be given for consolidation. These treatments are given at 3-4 week intervals.

Things are a little harder for patients who are grouped as ‘high risk’. This category of patients is treated with curative intent only if they have an HLA-identified sibling. What is meant by “HLA-identified sibling”? HLA can be simplified as a marker of the tissues. Different people differ in their HLA type. If two persons are HLA compatible, it means that their tissues are also more or less identical to each other. So, tissues can be transplanted between such people without getting rejected. Why do they need a HLA-identified sibling?

It is because the treatment may need stem cell transplantation and these stem cells can only be taken from a HLA-identified sibling for it not to be rejected.

Most of the people with acute myeloid belongs to the elderly age group, but it is a very sad situation because those patients cannot be treated with curative intent, because the treatment it self carries a very high morbidity rate for elderly patients. The toxicity of the treatment is very high so that they cannot bear that much of toxicity.

There is another group of patients who are at intermediate risk. In these patients remission is induced by giving consolidating chemotherapy. Thereafter they will be treated with sibling matched allogenic transplantation.   

With all above mentioned interventions, 75% of the patients who are under 60 years of age may achieve complete remissions. If a patient fails to achieve complete remission it could be due to one of the following causes.

1.      Resistant leukaemia

2.      Infection – the disease and the treatment both make the patient Immunocompromised. Therefore, they are more prone to get infections and these infections can be severe enough to cause death.

3.      Bleeding – The patients may become severely thrombocytopenic and that could lead to fatal haemorrhage. This is a rare cause of failure of treatment.

Only half of the patients who successfully achieve complete remission will get completely cured. Recurrence of the disease is sign of bed prognosis because it is very hard to achieve a longer life time when the disease recurs. The prognosis found to be bad even the physicians are able to achieve a second remission. The only thing that improves the survival rate is allogenic transplantation.

Still the patients with acute myeloid leukaemia should not give up their hopes because there are a lot of experimental therapies going on at the time.

References : Kumar P and Clark M, 2009. Clinical Medicine. 7th ed.

What is Consolidation in Leukaemia and Why it is Important?

I have described what remission induction in my previous posts. This remission induction is followed by consolidation. Simply, consolidation means giving further treatment, so the patient won’t have the disease again. Consolidation is achieved by giving further treatment when the patient remits. If not, the disease will reappear invariably. The following factors determine whether consolidation will be done or not.

·         Type of leukaemia

·         Patient risk factors

·         The patients tolerance of treatment

Why consolidation is important?

Even though remission induction means bringing the bone marrow and the blood in to normal state, there could be still some leukaemic cells remaining in the bone marrow, undetected. So, these cells can multiply and the disease can relapse. Therefore, there should be a way to prevent these cells from raising their heads. This is where consolidation comes into play. The continuation of the treatment prevent the disease from relapsing again.

References : Kumar P and Clark M, 2009. Clinical Medicine. 7th ed.

Treatment for acute Leukaemia

The following treatment options are available for the patient with acute leukaemia.

1.      Palliative Therapy

2.      Curative Therapy

3.      Active Therapy

Palliative Therapy

Palliative therapy involves both chemotherapy and radiotherapy. The patient is given the opportunity to stay at home as much as possible.

Curative Therapy

This is only done if the benefits outweigh the risks; since the treatment itself carries a considerable morbidity (also read Why Everybody with Acute Leukaemia is not Treated with Curative Intent). The cure can never be guaranteed or even expected in some of the cases. So, it is a controversial issue whether to start treatment of not. This is carefully discussed among the physician and the patient. 

 Curative therapy is given only in specialized centers which handles only about 10 such cases per year. Therefore the patient may have to be transferred to one of such centers. It also involves long term hospitalization. In the first instance the patient will have to be hospitalized for about a month and subsequent admission for several days to weeks. So the patient may have to discuss about their work pale/education, etc.

Even after the successful therapy life won’t be the same for some of the patients.

 Active Therapy

This involves supportive care and specific treatment. 

Supportive Care

Supportive care is targeted at providing comfort to the patient. It treats only for the symptoms. So the each symptom is treated separately.

·         For anaemia – most of the symptoms in leukaemia is due anaemia. So, it is corrected by repeated blood transfusion (packed red cells). Everybody with leukaemia is not transfused with blood. Only those who have severely reduced haemoglobin are transfused.

·         For thrombocytopenia – as mentioned in my previous posts, thrombocytopenia means reduced platelet counts. Their reduction in number results in bleeding tendencies. So the patients bleeding tendencies should be controlled. The exact platelet count is determined before the beginning of the treatment and the decision whether to transfuse or not is taken according to the platelet count. The platelet counts requiring transfusion in uninfected is <10×10⁹ /L and that in infected is <20×10⁹ /L.

·         For leucopenia – As I have mentioned in my previous posts the reduction of white blood cells leads to higher risk of infections. So these infections should be treated. Some of the patients may not have already developed any infections but still they should be treated prophylactically. Prophylaxis means treating in order to prevent a disease. Prevention does not only involve medication. It also contains education of patients, relatives and staff about hand washing and other hygienic activities. That’s why such patients are isolated in hospitals. Appropriate antifungals and antibiotics will be chosen by the physician and prescribed.

Infected patients are treated therapeutically with appropriate antifungals and antibiotics.

·         Another problem they might develop is hyperuricaemia. This condition is treated with hydration and prophylactic alopurinol and rasburicase. So, the patient will be asked to drink plenty of water.  

Specific treatment 

This is targeted in bringing the blood and bone marrow to their normal state. The therapy it self impairs bone marrow function. Therefore, it carries the risk of life threatening bone marrow function. Therefore, the treatment is carried out in a hospital where the patient has his/her separate room, lavatory facilities and lesser risk of infection.

A venous catheter is inserted in to the patient and Cytotoxic drugs are administered through this line. Remission induction and consolidation are achieved.

References : Kumar P and Clark M, 2009. Clinical Medicine. 7th ed.