Acute Lymphoblastic Leukemia (ALL)

Acute lymphoblastic leukemia (ALL) is an atypical form of cancer that affects nearly two hundred adults annually in the UK.

Leukaemia is the cancer caused due to the uninhibited proliferation of the white blood cells due to which these cells cannot reach maturity.

In acute lymphoblastic leukemia, there is unrestrained production of the immature lymphocytes known as lymphoblasts (at times called as blast cells). There are two varied kinds of lymphocytes, namely: B-lymphocytes and T-lymphocytes.

These immature cells inundate the bone marrow and impede proper functioning of blood cells production. Since the leukemia cells have not attained total maturity, they fail to carry out the task of normal white blood cells leading to a heightened likelihood of infections. As the bone marrow is crammed with immature white blood cells, it cannot produce adequate amounts of healthy red cells and platelets.

ALL is more prevalent among children below the age of fifteen years as compared to adults. When detected in teen years or among adults, ALL is more frequent in those individuals lying in the age band of 15-25 years and in elderly persons. It is more commonly detected in men as compared to women.

On the basis of the WHO system, ALL is classified on the basis of the lymphocyte type (B- or T-lymphocyte) that has turned malignant, into three varied sub-types:

• Early (precursor) B-lymphoblastic leukemia (majority of the adults detected with ALL are believed to be having this type)
• Mature B-lymphoblastic leukemia (at times known as Burkitt-type ALL as it is alike Burkitt syndrome)
• Early (precursor) T-lymphoblastic leukemia.

Acute Lymphoblastic Leukaemia Causes and Risk Factors:

There is ongoing research to understand the cause of ALL. ALL, like other cancer types, is non-contagious.

Studies have revealed that the risks of getting acute lymphoblastic leukemia are not augmented due to:

• Being exposed to electromagnetic fields.
• Residing close to high-voltage electricity cables.
• Radon presence in households.

There are several risk factors that could raise the chances of developing ALL, namely:

• Radiation – Being exposed to soaring levels of radiation, for instance, in the event of a nuclear accident or an atom bomb. Increasing number of leukemia cases have been observed among those residing near nuclear power plants.
• Genetic Constitution – ALL is mostly not the outcome of an inherited flawed gene. However, those with particular heritable disorders inclusive of Down’s syndrome and Fanconi’s anaemia have been observed to be at a heightened risk of developing leukemia.
• Chemical Exposure – In atypical cases, leukemia might be cited in those that have had exposure to chemicals like benzene and other kinds of solvents that are utilised for industrial purposes.
• Infection – ALL is believed to be caused due to the chain of genetic variations in a certain group of under-developed blood cells. It is still unclear as to the causes behind these genetic variations, but infection might be playing a significant part in the process. Though, no definite infections that lead to leukemia have been detected.

Acute Lymphoblastic Leukaemia Symptoms:

• Sense of paleness occurring due to anaemia caused because of the dearth of red blood cells.
• Tiredness, breathlessness in spite of no major exertion.
• A general sense of unwell and feeling below par, possibly due to throat or mouth soreness.
• Joint and bone aches. The bones might be affected due to leukemia cells.
• Recurrent infections due to the dearth of healthy white blood cells that lowers immunity.
• Abnormal bleeding – This could occur due to lowered platelet count. This could include bruises appearing without any evident injury, heavy menstrual cycles among women, gums that bleed easily and recurrent nose bleeds.

On certain occasions, an individual would be asymptomatic and leukemia is detected only during the routine blood analysis.

Signs of acute lymphoblastic leukemia might occur swiftly in some weeks and prompt treatment might become necessary.

Diagnosis & Tests:

• An abnormal outcome of a blood test could point to the presence of ALL. In such a situation the haematologist specialising in treating blood problems would order visiting a hospital in order to undergo additional tests and treatment.
• The doctor after taking into account the detailed medical history would carry out a physical examination and a particular kind of blood test that detects the count of all the varied forms of blood cells. If the outcome of the blood test reveals the presence of leukemia, then the doctor would extract a small sample of bone marrow for analysing the particular kind of leukemia present, which will assist in charting out the line of treatment.
• Bone marrow biopsy – Under the influence of local anaesthesia, a bone marrow sample is extracted with the help of a fine needle from the back of the pelvic area or the hip bone or infrequently from the sternum (breast bone) to be sent for microscopic analysis for detecting anomalous white blood cells. During the 15-20 minutes procedure performed in the ward or the outpatient facility, the needle is pierced through the skin all the way into the bone, following which a small bone marrow sample is removed into a syringe that could cause some level of pain or discomfort. A fast-acting sedation medicine would be given for allaying the pain during the test. At times, a small bone marrow core might be required for testing using a procedure known as trephine biopsy and could require a couple of minutes more. A special kind of needle is inserted through the skin till the bone marrow. The needle tip is tailored to incise out a sample of bone marrow. Bruising and aches might be felt subsequent to the test that could be lowered by taking mild pain-relieving medicines.
• Cytogenetic Testing – This test done on the blood and bone marrow involves chromosome testing to check for any specific alterations in the chromosomes, as varied kinds are linked with specific genetic alterations.
• Immunophenotyping – This test done on the blood and bone marrow sample reveals what kind of lymphocyte has turned malignant. Immunophenotyping could help in deciphering whether the leukemia originated from either B-lymphocytes or T-lymphocytes. Detecting what kind of lymphocyte has been affected, assists the doctors in charting out the most apposite treatment alternative.
• Chest x-ray – These are taken for checking whether there are any symptoms of inflamed lymph glands in the chest region.
• Lumbar puncture – Under the influence of local anaesthesia a small amount of cerebrospinal fluid sample is taken from the lower portion of the back via a needle injected till the spine. Lumbar puncture lasts for few minutes and might become painful. Few experience headache subsequently. The doctor would prescribe painkillers. Subsequently, one would be needed to lie down flat for a span of few hours.
• Other Scanning Procedures – An ultrasound, MRI and CT scans could be performed for detecting whether leukemia has metastasized to other body parts.

Acute Lymphoblastic Leukaemia Treatment:

Chemotherapy – Chemotherapy employs the use of cancer-combatant (cytotoxic) drugs for obliterating leukemia cells by interrupting their production. The drugs flow through the body after being intravenously administered. As these drugs are incapable of gaining entry into the cerebrospinal fluid (CSF), they need to be directly infused via a lumbar puncture. This is carried out in spite of leukemia cells not being spotted in the CSF, as research has revealed that there is definite possibility of some of the leukemia cells always been present in the CSF which would require eradication.

In men the drugs fail to reach the testes. Hence, additional treatment might become requisite when chemotherapy is given into the CSF that at times is merged with radiotherapy given to the brain. Radiotherapy might be given to the testes in men. Radiotherapy when given in this manner to the brain and the spinal cord or testes is called prophylactic radiotherapy.

Chemotherapy for treating acute lymphoblastic leukemia is offered in three varying phases, namely:

Induction

This is the foremost intensive treatment intended at wiping out major populace of the leukemia cells. It generally attains a reduction of the disease implying that the leukemia cells could not be henceforth spotted during microscopic analysis.

Drugs employed during this phase would comprise of daunorubicin, vincristine (Oncovin), methotrexate, cyclophosphamide, cytarabine (Ara C), mercaptopurine (Puri-Nethol). Steroids and drugs like allopurinol and folinic acid might additionally be given.

Intensification

At times, up to four intensive course of chemotherapy are generally offered to raise the probability of recovery. The drugs given in this phase could comprise of high-dosage methotrexate, vincristine, cytarabine, etoposide, daunorubicin, cyclophosphamide, tioguanine (Lanvis) and at times steroids might be given. Imatinib (Glivec) could be given to those having Philadelphia chromosome either alongside or as an alternative to chemotherapy during this phase.

Maintenance or Continual therapy

This tablet course of comparatively lesser intensive chemotherapy course is intended at obliterating any remnant leukemia cells. The drugs that might be used in this phase are mercaptopurine, methotrexate, vincristine, cytarabine (administered in the CSF). Steroids and antibiotics could also be given and Imatinib (Glivec) might be continued in this phase.

In case one is undergoing standard continual chemotherapy then the entire chemotherapy course would continue for at least 2 years. In case of high-dose chemotherapy following induction and intensification phase, the treatment would be shorter and last for lesser than a year.

How Is Chemotherapy administered?

Few drugs are given in pill form, but the key induction and intensification treatments comprise of a mixture of nearly 4 drugs given intravenously by two ways:

Central Line

In order to simplify the chemotherapy and to avert repeated injections, a fine pliable tube (central line) could be inserted into a vein in the chest under the influence of general /local anaesthesia via a small incision. The other tip of the tube is located outside the body with a facility to cap it when not in use. The tube is the conduit way for giving drugs, fluids, stem cells or bone marrow and for collecting blood samples.

Soreness and discomfort might be experienced for few days following the line being inserted, though the pain should subside thereafter. The line could remain for up to 2 years and the patient would be shown how to properly take care of the tube to avert any kind of blockages or infections.

PICC line and the implantable port

Optionally, a PICC line or an implantable port might be employed that is inserted into a vein in the crook of the arm.

Intrathecal chemotherapy

Chemotherapy mostly administered directly into the cerebrospinal fluid is known as intrathecal chemotherapy.

Side effects due to Chemotherapy

• Likelihood of easy and heavy bruising, bleeding , blood patches (petechiae) or rashes (purpura).
• Lowered immunity.
• Anaemia.
• Sense of unwell, weariness, oral sores.
• Hair loss.

Steroid Therapy

Steroids are drugs mostly administered alongside chemotherapy to assist in annihilating the leukemia cells. The two widely employed steroids are Prednisolone or dexamethasone. They are given in tablet form for just few days in a month. Hence, the associated side effects are fewer that include increased food craving, sense of greater energy and sleeplessness.

In case steroids are taken for some periods of time then the transitory side effects usually include bloating, high blood pressure, digestive disorders and a slight increase in the likelihood of contracting infections. The body’s blood glucose levels might also soar for which the doctor would recommend drugs for normalising the blood sugar levels.

Radiotherapy

Radiotherapy uses high-power beams for killing the cancerous growth while preserving as much as normal cells as possible. In cranial radiotherapy the treatment is given to the head. The treatment would be given for five days in a week lasting for 2 weeks and for 8 to 10 sittings.

In case one needs a high-dosage treatment alongside stem cell support, then a specialised form of radiotherapy known as total body irradiation or TBI is given. The radiotherapy is offered to the entire body to obliterate the bone marrow cells.

Initially for a couple of visits, x-rays of the areas to be treated would be taken by using a large device known as a stimulator.

In cranial radiotherapy, a transparent plastic mask shaped to the precise contour of the head and neck is fitted to maintain correct stance during the treatment. Marks are drawn on the mask for demarcating the treatment location.

In case the mask is not being used, the marks would be made on the skin and at times small permanent marks would also be made on the skin.

Radiotherapy does not cause any pain, however one would need to stay motionless during the few minutes the treatment lasts.

Side effects

• Hair loss.
• Extreme weariness.
• Sleepiness.
• Feeling nauseous and sick.
• Low appetite.

Imatinib (Glivec)

This drug as called as the signal transduction inhibitor (capsule form) could be used while treating those with Phildelphia chromosome positive ALL. Glivec functions by hampering signals within the leukemia cells that causes them to become irregular and continue to spread. By obstructing the signals, the cells face imminent death.

Glivec might lead to side effects like feeling unwell, at times diarrhoea, aches and cramps in the limbs, skin rashes, facial swelling particularly in the surrounding eye area.

High-dose Stem Cell Transplant

Stem cell transplant allows more elevated doses of chemotherapy to be given than what is normally given. Elevated chemotherapy doses, at times along with radiotherapy are given spanning a couple of days to aid in improving the likelihood of treating leukemia or to prolong a reduction in the disease.

The high-dose treatment is used in case the ALL has relapsed following treatment or is of a type that has high likelihood of recurrence following initial chemotherapy session.

The two means of carrying out the transplant is by:

• Making use of the own stem cells.
• Stem cells derived from a donor.

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