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Acute Lymphoblastic Leukaemia

Acute Lymphoblastic Leukaemia (ALL) is a type of cancer of the blood & bone marrow – the spongy tissue inside bones where blood cells are made. ALL is more prevalent among children than among adults.

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Overview

Acute Lymphoblastic Leukaemia (ALL) or Acute Lymphocytic Leukaemia is a type of cancer that affects the blood and bone marrow, the spongy tissue inside bones where the blood cells are produced. Acute lymphoblastic leukaemia is caused by the overproduction of immature white blood cells called lymphoblast or leukaemic blasts.

Since the bone marrow is unable to make adequate numbers of red cells, normal white cells and platelets, people with ALL become more susceptible to blood disorders, such as anaemia, recurrent infections, bruising and bleeding.

As the disease progresses, leukaemic blast cells get into the bloodstream and accumulate in various organs, namely lymph nodes, spleen, liver and central nervous system (brain and spinal cord). ALL is more prevalent among children than it is among adults.

Types

The World Health Organisation (WHO) has classified ALL into the following types:

1. Pre-B-cell ALL: It accounts for approximately 80-85% of cases among children. It is the type of ALL arising in the B-lymphocytes that are in their early stages of development in the bone marrow.

2. B-cell ALL: B-cell ALL arises in mature lymphocytes. This form of ALL is relatively rare and accounts for less than 2% of childhood ALL cases. B-cell ALL is also called Burkitt-like or Burkitt-type ALL.

3. T-cell ALL: Approximately 15% of ALL cases among children are diagnosed to be T-cell ALL. This variety ALL is further categorised to early, mid or late T-cell ALL based on the maturity of the affected cell. This ALL type is distinguished by high white blood cell count and involvement of the CNS during the diagnosis.

Symptoms

All major symptoms of acute lymphoblastic leukaemia are caused due to poor circulation of normal blood cells. ALL advances quickly, and the patients are unwell only for a short period of time (days or weeks) before they are diagnosed.

Common symptoms of ALL include:

  • Anaemia caused due to reduced red blood cells (RBCs) production
  • Persistent tiredness, dizziness, paleness or shortness of breath when physically active caused due to anaemia
  • Increased risk of infections
  • Increased or unexplained bleeding or bruising due to poor platelet count
  • Bone or joint pain due to overproduction of leukaemic blast cells

Other symptoms include chest pain, swollen lymph nodes and abdominal discomfort caused by swollen spleen or liver.

Some of these symptoms are seen in other illnesses, such as viral infections as well; therefore, a proper examination is necessary for accurate diagnosis and appropriate treatment.

Causes

While the exact causes of ALL are not known, this disease is believed to result from mutations in the genes that are responsible for blood cell development and growth.

Studies conducted to find the possible causes of this disease have identified certain factors that are associated with increased risk of this disease:

  • Exposure to Radiation: Exposure to high doses of radiation either accidentally or therapeutically
  • Exposure to Harmful Chemicals: Exposure to industrial chemicals, namely benzene, pesticides, and certain chemo drugs used to treat other forms of cancers
  • Infections: Certain types of viral infections
  • Specific Genetic Disorders: Certain genetic disorders like Down syndrome and Fanconi anaemia increase the risk of developing ALL.
  • Poor Immunity: An overall weakened immune system may also increase the risk of ALL.

Diagnosis

Acute lymphoblastic leukaemia is usually diagnosed by examining blood and bone marrow samples.

a. Full Blood Count: The diagnosis of ALL begins with a Full Blood Count (FBC) or Complete Blood Count (CBC). The specialist will collect the blood sample from a vein in the arm and will investigate it in the laboratory. The presence of these blast cells in the blood sample suggests ALL. This primary diagnosis of ALL should be confirmed through bone marrow examination, and the confirmed diagnosis will be followed by appropriate treatment.

b. Bone Marrow Examination: A bone marrow biopsy is suggested in order to confirm the primary diagnosis. For this test, the bone marrow sample is collected from the back of the hip bone. This sample is examined under the microscope to find out the number and type of cells present and the rate at which the haematopoiesis (blood cell production) activity is happening. The diagnosis of ALL is confirmed if overproduction of blast cells is witnessed.

c. Further Testing: Once ALL is confirmed, blood and bone marrow cells are examined further using special laboratory tests, which include immuno-phenotyping, cytogenetic and molecular tests. These tests help gather information such as the exact type of disease, the stage and the best way to treat it. A small sample of the cerebrospinal fluid (CSF) is also collected through a procedure called lumbar puncture. This fluid is tested in the laboratory to check if the leukemic cells have spread to the central nervous system.

Chest x-rays and baseline blood tests could also be performed to study the kidney and liver functions.

Treatment

ALL is one such cancer that progresses quickly, and therefore, it has to be treated as soon as it is diagnosed. Multiple factors are to be considered before devising a treatment plan, and they include the subtype and stage of ALL, the patient’s age and the overall health. Following are the common methods used to treat ALL:

a. Chemotherapy: While treating ALL with chemotherapy, a combination of drugs, including steroids is administered in multiple cycles for a specific period of time. The primary goal of chemotherapy is to destroy all the leukaemic cells and induce remission.

Chemotherapy is administered in multiple ways namely intravenously (through veins), intramuscularly (through muscles) or orally (in tablet form). In a few cases, chemotherapy drugs are also administered intrathecally into the spinal canal; this is done to prevent the disease from spreading to the central nervous system.

Chemotherapy for ALL is administered in three main phases:

  1. Induction Therapy: This phase involves an intensive course of treatment with a primary goal to destroy all the leukaemic cells in the blood and bone marrow and restore normal blood cell production. This phase may last for a month or so.
  2. Consolidation (post-remission) Therapy: This phase follows the induction phase and may last for a few months. Consolidation therapy destroys any remaining leukaemic cells after induction therapy. Consolidation therapy helps in reducing the risk of relapse.
  3. Maintenance Therapy: Maintenance therapy is administered to prevent relapse and help the patient lead a cancer-free life. During this phase, the chemotherapy drugs are given in much lower doses. Common maintenance protocols involve chemotherapy tablets or injections with courses of corticosteroids. Maintenance therapy usually lasts for several months.

b. Bone Marrow Transplantation: Bone marrow transplant is used as a treatment protocol for acute lymphoblastic leukaemia, especially if the risk of relapse is high. This procedure the faulty bone marrow cells with the healthy ones and thereby the production of normal blood cells is restored.

Before the transplantation, high dose chemotherapy or radiation therapy is administered in order to destroy the marrow cells that are producing leukaemia cells. Later, the healthy marrow cells are transfused into the patient’s body.

c. Radiation Therapy: Although not standardised treatment, radiation therapy is recommended for ALL patients in the following conditions:

  • To treat or manage the ALL that has spread to the brain or spinal cord
  • To destroy the leukaemic cells completely before the bone marrow transplantation
  • To relieve pain in the cases where the ALL has spread to pain (as a part of palliative therapy)

d. Targeted Therapy: Targeted therapy works by targeting specific molecules present on the surface of the leukaemic cells in ALL patients. Targeted therapy could work by blocking the components that signal leukaemic cells to divide and grow or destroy them.

Frequently Asked Questions

1. What is the difference between acute and chronic lymphocytic leukaemia?

Acute leukaemia progresses quickly with severe symptoms and needs immediate medical attention. This is because the cancer cells in acute lymphocytic leukaemia patients divide rapidly.

Chronic lymphocytic leukaemia, on the other hand, progresses slowly and the early symptoms are mild in most cases and therefore go unnoticed.

2. Can acute lymphoblastic leukaemia be detected in a blood test?

Yes, ALL can be detected in a blood test. To confirm the findings from the blood test, a few more tests such as bone marrow examination, immune-phenotyping, etc., may be recommended.

3. Does acute lymphocytic leukaemia run in families?

There is no sufficient evidence on acute lymphocytic leukaemia being hereditary.

However, individuals with certain genetic disorders, which could be inherited from the parents, may have an increased risk of developing ALL. The key genetic disorders include:

  • Down syndrome
  • Li-Fraumeni syndrome
  • Fanconi anaemia
  • Klinefelter syndrome
  • Bloom syndrome
  • Ataxia-telangiectasia
  • Neurofibromatosis
4. How is acute lymphocytic leukaemia prevented?

Since the actual cause of acute lymphocytic leukaemia is unknown, experts are not fully aware of the measures that can be taken to prevent this disease.

However, there are few risk factors that are associated with acute lymphocytic leukaemia, such as exposure to hazardous chemicals and radiation, having a poor immune system, etc. Avoiding exposure to hazardous chemicals and radiation and having a healthier immune system could help in reducing the risk of developing this disease.

5. Do I still have to receive chemo when in remission?

Yes, for a few diseases like ALL, you will have to receive chemotherapy even after achieving remission. The main goal of administering chemotherapy when you are in remission is to prevent cancer from coming back. It is called maintenance therapy, and it may go on for up to 2 years.

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