ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
What is Acute Lymphoblastic Leukemia?
Acute Lymphoblastic leukemia (ALL) is a cancer that starts from white blood cells called lymphocytes in the bone marrow (the soft inner part of the bones, where new blood cells are generated).
The term “acute” means that the leukemia can progress quickly, and if not treated, would probably be fatal within a few months. ‘Lymphoblastic’ means it develops from early (immature) forms of lymphocytes, a type of white blood cell.
Acute Lymphoblastic Leukemia is the commonest childhood cancer. This arises from abnormalities in the precursors of normal lymphocytes which are otherwise a normal part of our immune system necessary to fight infections. These abnormal cells rapidly fill up the bone marrow space suppressing the normal cells.
In most cases, the disease is characterized by certain abnormalities in the chromosomes which promote abnormal growth of certain lymphoid cells rather than maturation to normal lymphocytes.
What Causes Acute Lymphoblastic Leukemia?
This is not known in most cases. However, exposure to radiation, exposure to high voltage electric lines in childhood and certain genetic disorders predispose to development of ALL.
What are the Symptoms of Acute Lymphoblastic Leukemia or Acute Lymphoid Leukemia?
- General weakness
- high temperature (fever)
- Weight loss
- Frequent infections
- Bruising easily or with no obvious cause
- Bleeding from the gums or nose
- A fine rash of dark red spots (called purpura)
- Blood in urine or stools
- Pain in the bones or joints
- Swollen lymph glands
- Enlarged liver or spleen
How do we Diagnose Acute Lymphoblastic Leukemia?
- Complete Blood Count: The characteristic finding of Acute Lymphoblastic Leukemia is high white blood cell count with low haemoglobin and platelets. Routine examination of the blood gives the diagnosis.
- Bone Marrow Examination: This is necessary for confirmation of the diagnosis. There must be more than 30% of abnormal cells (Blasts) in the bone marrow to call it leukemia.
- Flow Cytometry: ALL has two broad subtypes- B cell Acute Lymphoblastic Leukemia and T cell Acute Lymphoblastic Leukemia. There are further subtypes in the individual categories. This has got implications on the choice of treatment and outcome. This is only possible by Flow Cytometry.
- Cytogenetics: This is testing for abnormalities in the chromosomes.
- Certain genes are brought next to each other by a process called ‘translocation’ leading to uninterrupted growth of these cells. The classical example is the translocation of a part of chromosome 9 to 22 resulting in the BCR gene juxtaposed to the ABL gene (called Philadelphia Chromosome). Both are normal genes, but when they interact they produce an abnormal protein which drives the cell growth. Several such translocations have been detected in ALL, such as 1:19, 12:21, 4:11 etc.
- The absolute increase (Hyperdiploid) or decrease (Hypodiploid) in the number of chromosomes in the affected cells is also a feature of ALL which tells us how the child is going to respond to a particular type of treatment.
- Certain changes in sequence of the genes called mutations are also seen which have an impact on outcome.
How do we classify Acute Lymphoblastic Leukemia to decide on the outcome?
Unlike cancers of solid organs, Acute Lymphoblastic Leukemia and other blood cancers are not staged by the extent of involvement. Certain features related to the patient, the disease and the impact of treatment are taken to account to classify them as Standard-Risk or Good-Risk, Intermediate-Risk and High-Risk.
- Age: if the patient is 2 – 10 years old, it is considered favourable
- Cytogenetics: Certain chromosomal abnormalities such as increase in number of chromosomes (Hyperploidy) and translocation 12: 21 are considered favourable. On the other hand, decrease in the number of chromosomes (Hypoploidy) and translocation of 9:22 and 4:11 are considered unfavourable.
- Response to Treatment: Response to steroids after 7 days is probably a very good indicator of how the disease is going to behave. Response after 4 weeks of chemotherapy gives further indication to this.
What is Minimal Residual Disease?
Minimal Residual Disease (MRD) means patient still has a minimum disease and has not fully recovered. Response to treatment is conventionally defined by the number of blasts we see under the microscope. If we see less than 5% such cells it is called COMPLETE REMISSION (CR).However, CR means that the number of leukemia cells in the body are less than 109 or 1000 million cells. Further treatment which spans over months of intensive treatment and years of oral treatment are geared to reduce the number of leukemia cells to a level where our immune system can eliminate the remaining cells.
MRD is the detection of cells below 1%, which can range of 1 in 1000 to 1 in a million cells. This enables us to monitor the effect of treatment and change, it if needed.
How do we treat Acute Lymphoblastic Leukemia?
Treatment for acute lymphocytic leukemia falls into following phases:
- Induction Therapy: Induction Therapy is the first phase of treatment to kill most of the leukemia cells in the blood and bone marrow and to restore normal blood cell production.
- Consolidation Therapy: Consolidation Therapy is also known as post-remission therapy. Consolidation therapy aimed at destroying any remaining leukemia cells in the body, like in the brain or spinal cord.
- Maintenance Therapy: It helps in preventing leukemia cells from regrowing. Treatments used in this stage are often given at much lower doses, over a long period of time, often years.
- Preventive treatment to the spinal cord: Patients suffering from acute lymphocytic leukemia may also receive treatment to kill leukemia cells located in the central nervous system during each phase of therapy. Chemotherapy drugs are often injected directly into the fluid that covers the spinal cord.
- Radiation Therapy: Radiation therapy uses high-powered beams, such as X-rays, to kill cancer cells. If the cancer cells have spread to the central nervous system, radiation therapy is also recommended.
Depending on patient’s evaluation, the phases of treatment for acute lymphocytic leukemia can span two to three years.
How is ALL in Adults different from that in Children?
- ALL is less common in adults
- Certain bad CYTOGENETICS such as Philadelphia Chromosome (translocation between chromosomes 9 and 22) are more common in adults.
- Adults do not tolerate intensive chemotherapy as well as children
- Only 30% of adults are cured by chemotherapy alone.
What is different about treatment of Acute Lymphoblastic Leukemia?
- ALL has a tendency to spread to the brain. Hence, the treatment involves givingintrathecal chemotherapy with drugs like methotrexate or cytarabine directly in the fluid around the brain and spinal cord by a procedure called Lumbar Puncture.
- Intravenous chemotherapy is also given over 6 months, followed by oral drugs for 18-30 months. Boys need longer treatment than girls.
BONE MARROW TRANSPLANTATION (BMT) FOR ADULTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA
- Most adults with ALL benefit from a Bone Marrow Transplant at the first remission
- Most adults beyond the age of 40 years cannot tolerate high doses of radiotherapy or chemotherapy and would need Reduced Intensity Conditioning for BMT.
- Once the disease recurs, the chance of achieving a second remission is much lower than in children.
How is Conditioning for BMT done in Acute Lymphoblastic Leukemia?
Total Body Radiation is an important component of conditioning for BMT.
What are the results of BMT in Acute Lymphoblastic Leukemia?
- BMT reduces the risk of relapse i.e. recurrence of disease by 50% compared to chemotherapy.
- BMT is the only cure for patients who relapse early after chemotherapy.